Search PubMed⌕ Search

Biomedical subjects

Z Shen

Publications and source records attributed to Z Shen.

At least 91 records · Page 5Linked to original sources
PubMed2000

Antiplatelet and antithrombotic effects of the diterpene spiramine Q from Spiraea japonica var. incisa.

Spiramine Q, a diterpene, was isolated from a Chinese herbal plant Spiraea japonica var. incisa Yu. Born's and Wan HY's methods were used to investigate effects of spiramine Q on rabbit platelet aggregation and serotonin release, respectively. Its antithrombotic effect in mice was also evaluated by Myers' method. Spiramine Q selectively inhibited arachidonic acid-induced platelet aggregation in vitro or ex vivo, and decreased serotonin secretion from rabbit platelets. Spiramine Q (5 mg/kg) decreased the mouse mortality caused by injection of 80 mg/kg arachidonic acid in the tail vein. The results suggested that spiramine Q showed potent antiplatelet and antithrombotic activites.

Animals↗
PubMed2000

Isolation and characterization of a Helicobacter sp. from the gastric mucosa of dolphins, Lagenorhynchus acutus and Delphinus delphis.

Gastric ulcerations in dolphins have been reported for decades. Some of these lesions were associated with parasitic infections. However, cases of nonparasitic gastric ulcers with no clearly defined etiology also have been reported in wild and captive dolphins. Considerable speculation exists as to whether dolphins have Helicobacter-associated gastritis and peptic ulcer disease. The stomachs of seven stranded Atlantic white-sided dolphins, Lagenorhynchus acutus, and 1 common dolphin, Delphinus delphis, were assessed for the presence of Helicobacter species. Novel Helicobacter species were identified by culture in the gastric mucosa of two of the eight dolphins studied and by PCR in seven of the eight dolphins. The gram-negative organisms were urease, catalase, and oxidase positive. Spiral to fusiform bacteria were detected in gastric mucosa by Warthin Starry staining. Histopathology revealed mild to moderate diffuse lymphoplasmacytic gastritis within the superficial mucosa of the main stomach. The pyloric stomach was less inflamed, and bacteria did not extend deep into the glands. The lesions parallel those observed in Helicobacter pylori-infected humans. Bacteria from two dolphins classified by 16S rRNA analysis clustered with gastric helicobacters and represent a novel Helicobacter sp. most closely related to H. pylori. These findings suggest that a novel Helicobacter sp. may play a role in the etiopathogenesis of gastritis and gastric ulcers in dolphins. To our knowledge this represents the first isolation and characterization of a novel Helicobacter sp. from a marine mammal and emphasizes the wide host distribution and pathogenic potential of this increasingly important genus.

Animals↗
PubMed2000

Helicobacter canadensis sp. nov. isolated from humans with diarrhea as an example of an emerging pathogen.

We recently analyzed 11 helicobacter isolates cultured from diarrhea patients in Canada. These isolates had been characterized biochemically by restriction fragment length polymorphism (RFLP; AluI, HhaI) analysis and by fatty-acid analysis as Helicobacter pullorum. However, four of the isolates differed biochemically from H. pullorum by their inability to hydrolyze indoxyl acetate and their resistance to nalidixic acid. Using complete 16S rRNA analysis, we determined that these four strains clustered near H. pullorum but had a sequence difference of 2% and therefore represent a novel helicobacter, Helicobacter canadensis. This novel helicobacter could also be distinguished from H. pullorum by RFLP analysis using ApaLI. The number of novel Helicobacter spp. associated with gastrointestinal disease in humans and animals is rapidly increasing. There are now six Helicobacter spp. isolated from diarrheic humans, the other five being H. pullorum, H. canis, "H. rappini," H. fennelliae, and H. cinaedi. This finding highlights the importance of careful molecular analysis in addition to standard biochemical tests in identifying the increasing number of Helicobacter spp. isolated from humans and animals.

Bacterial Typing Techniques↗
PubMed2000

Long-term survey of outcome in acute promyelocytic leukemia.

OBJECTIVE: To investigate all-trans retinoic acid (ATRA) and As2O3 which were found to be able to selectively induce differentiation and apoptosis in acute promyelocytic leukemia (APL) and recently became standard treatment for de novo or relapsed APL. The results of long-term follow up in 72 APL patients were presented and prognostic factors discussed. METHODS: Seventy-two newly-diagnosed patients with APL entering CR with ATRA were consolidated with chemotherapy alone (31 patients), ATRA + chemotherapy (30 patients) and ATRA alone (11 patients). Univariate analysis was done to identify the potential prognostic factors. A total of 40 cases of patients relapsed after their first complete remission, including 3 groups of patients: group A, patients treated with ATRA and chemotherapy after relapse (8 patients); group B patients treated with As2O3 alone for 2nd CR and consolidation (21 patients); group C patients treated with As2O3 for 2nd CR and both As2O3 and chemotherapy for consolidation (11 patients). Univariate analysis was also done to identify the potential prognostic factors. RESULTS: With a median follow-up of 45 months (5-75 months), the median event-free survival was 21 months and median overall survival was not achieved. The estimated 3- and 5-year event-free survival (EFS) and over-all survival (OS) were 32.5 +/- 10.5%, 18.4 +/- 7.5% and 73.8 +/- 17.5%, 58.5 +/- 15.2%. In denovo patients, the combination of ATRA and chemotherapy in both induction and post-remission treatment was found to be statistically significant for EFS (P = 0.023), and initial peripheral leukocyte count was significantly related to OS. In relapsed patients, only the treatment of As2O3 with or without chemotherapy in consolidation after relapse was statistically significant for CR and both EFS (P = 0.0061) and OS (P = 0.0013). CONCLUSION: ATRA is an effective induction therapy and can be considered as first choice of treatment in denovo APL. Addition of chemotherapy in both induction and post-remission therapy can delay or decrease the possibility of relapse compared to ATRA alone. As2O3 is an effective agent for relapsed APL and remains an important prognostic factor for relapsed APL.

Adolescent↗
PubMed2000

[Progress in researches on the function of PML gene].

This paper was aimed to review and expound the progreses in studies on biological fuction of wild-type PML gene and hence to have a gain in knowledge about the carcinogenesis of PML-RARalpha protein. Related reports issued at home and abroad and some research results from this institute were collected and reviewed. According to the data collected PML gene has many biological activites. High expression of PML gene can inhibit the growth of cells and induce apoptosis; PML gene is possibly involved in the regulation of gene expression. Moreover, the function of PML gene is related to its three important domains and its nuclear location; PML gene is associated with carcinogenesis of APL.

Animals↗
PubMed2000

[Measure of vibration protection effect of driver's corset and analysis of its biomechanical effect].

The purpose of this study was to evaluate the vibration protection and biomechanical effect of driver's corset. The frequencies of vertfical and horizontal vibrations were measured at low back of driver. The vehicle driven was ISUZU truck (loading capacity 8 tons). Vibration of the driver's lumbar back was measured real time with wear corset and without wear corset when the truck loaded with 6 tons was driven at the spead of ten, thirty and sixty kilometers an hour on the asphalt road. The results showed: 1. Vibration frequencies at driver's low back was under 10 Hz. It is a low frequency vibration. 2. The value of vertical vibration was higher than the value of horizontal (back and forth) vibration. 3. The vibration value of wear corset was higher than un-wear corset. These indicate the driver's corset is effective for protecting lumbar spine by means of change in the biomechanical characteristics and the resonace requencies of lumbar spine. So the driver's corset is one of the good methods for preventing the back pain of drivers.

Automobile Driving↗
PubMed2000

Recombinant bovine basic fibroblast growth factor accelerates wound healing in patients with burns, donor sites and chronic dermal ulcers.

OBJECTIVE: To evaluate the effect of recombinant bovine basic fibroblast growth factor (rbFGF) on accelerating healing of burn wounds, donor sites and chronic dermal ulcers in multicenters. METHODS: One thousand and twenty-four patients with burns, donor sites and chronic dermal ulcers were recruited for this prospective and multicenter clinical trial and another 641 patients with the similar wounds were used as controls. All patients were divided into three groups: burn group, donor site group, and chronic dermal ulcer group. In the burn group, 654 patients with superficial second-degree burns(superficial II degree) or deep second-degree burns(deep II degree) were treated topically with either recombinant bovine basic fibroblast growth factor (rbFGF plus vehicle, rbFGF 150 AU/cm2/day, 330 patients) or placebo (vehicle without rbFGF, 324 patients). In the donor site group, 509 patients were treated with rbFGF and 317 patients with placebo in a similar way as described elsewhere. In the chronic dermal ulcer group, 185 patients were treated with rbFGF and the controls were themselves. Photography, histological evaluation and clinical examination were used to evaluate the results of wound healing. RESULTS: All of superficial second-degree burns, deep second-degree burns and the donor sites treated with recombinant bovine basic fibroblast growth factor had an accelerated rate of granulation tissue formation and epidermal regeneration as compared with that in the controls. Superficial second-degree burns and deep second-degree burns treated with recombinant bovine basic fibroblast growth factor healed in 9.89 +/- 2.45 and 17.04 +/- 4.56 days, respectively, whereas the average healing time in those receiving placebo was 12.35 +/- 2.74 and 21.21 +/- 4.88 days. The donor sites treated with rbFGF or placebo healed in 10.68 +/- 4.55 and 14.74 +/- 6.46 days, respectively. All chronic dermal ulcers except 12 patients treated with rbFGF healed within 6 weeks. Histological evaluation of punch-biopsy specimens from the burn wounds, donor sites and chronic dermal ulcers seven days after treatment supported the impression of accelerated wound healing after rbFGF treatment. CONCLUSIONS: rbFGF is effective in shortening the wound healing time and improving the wound healing quality. Accelerating wound healing is of clinical benefit in reducing the length of hospitalization, costs and emotional burden of the patient.

Adolescent↗
PubMed2000

Hemostatic abnormalities associated with acute promyelocytic leukemia and corrective effects of all-trans-retinoic acid or arsenic trioxide treatment.

OBJECTIVE: To study in vivo effect of all-trans-retinoic acid (ATRA) or arsenic trioxide (As2O3) on the expression of tissue factor (TF) and the hemostatic disorders, a series of parameters were measured in bone marrow blasts and plasma from acute promyelocytic leukemia (APL) patients. METHODS: The plasma variables were measured by ELISA or chromogenic study. The TF transcription was assessed using reverse transcription-polymerase chain reaction technique (RT-PCR). RESULTS: The blast cell procoagulant activity (PCA), TF antigen of APL cell lysates, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As2O3 therapy. The plasma level of platelet alpha-granular membrane protein-140, soluble fibrinomonomer complex, thrombomodulin, tissue plasminogen activator and D-dimer significantly increased, fibrinogen, antigen level of protein C, plasminogen, alpha 2-plasminogen inhibitor and plasminogen activator inhibitor decreased at diagnosis, were restored to normal after complete remission but protein C activity and protein S remained elevated in ATRA group. CONCLUSIONS: There existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As2O3 therapy down-regulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, inhibited coagulation activation, secondary hyperfibrinolysis and recorrected other hemostatic abnormalities, thus greatly improved the bleeding symptom in early stage of the treatment.

Adolescent↗
PubMed2000

Impact of RT-PCR monitoring on the long-term survival in acute promyelocytic leukemia.

OBJECTIVE: To evaluate the impact of kinetics of molecular remission via retro-transcriptase polymerase chain reaction (RT-PCR) assay on the long-term survival in patients with acute promyelocytic leukemia (APL). METHODS: Seventy patients with newly-diagnosed APL in remission were involved in this study. Monitoring of minimal residual disease (MRD) was performed regularly by RT-PCR assay for PML-RAR alpha during consolidation. RESULTS: A 5-year relapse-free survival (RFS) and overall-survival (OS) were estimated as 46.8% +/- 8.4% and 69.9% +/- 9.4% for the whole group. Fifty-two (74.3%) patients got negative RT-PCR result at least once. Serial monitoring of RT-PCR was available in 38 cases and 24 (63.2%) patients presented with persistent negative PCR results. The achievement and continuous negative RT-PCR result was significantly related to the RFS. CONCLUSIONS: Achievement of negative RT-PCR in remission is associated with favorable RFS and OS. Continuous negative RT-PCR results are associated with long-term relapse-free survival and may be considered as potentially curative. RT-PCR assay for detection of MRD should be performed regularly during post-remission period as an important prognostic factor.

Adolescent↗
PubMed2000

Acute fatty liver of pregnancy: diagnosis and management of 8 cases.

OBJECTIVE: To investigate the early recognition and management of acute fatty liver of pregnancy (AFLP) to improve maternal and fetal survival. METHODS: Eight cases of AFLP seen in our hospital during the past three years were studied retrospectively. Symptoms, laboratory findings, timing of liver biopsy, and maternal and fetus outcome were assessed. RESULTS: The mean gestational age at onset was 34 +/- 2 weeks. All cases were primigravida. In the early stages, all patients presented malaise, nausea, vomiting and epigastric distress followed by jaundice in the third trimester of pregnancy. LABORATORY FINDINGS: all had raised transaminases and serum bilirubin (32.5-510.8 mumol/L), hypoalbuminemia (22.4-30.0 g/L), hypofibrinogenemia (< 180 mg/dl), prolonged prothrombin time and prolonged partial thromboplastin time. Maternal complication included hepatic encephalopathy (6 cases), ascites (6), hypoglycemia (5), hematemesis (2), and postpartum hemorrhage (5) and preeclampsia (4). Emergency cesarean section was performed in 3 cases. One mother died of fulminant hepatic failure and the others survived. There was no fetus death. Liver biopsy was done on the 5th to 15th postpartum day in 8 cases. CONCLUSION: With increasing awareness, especially in the early recognition of milder cases, and prompt progressive management including early termination of pregnancy by cesarean section and large dose infusion of fresh frozen plasma and albumin alternately, the prognosis of AFLP can be improved.

Acute Disease↗
PubMed2000

Relationship between gene expression of nitric oxide synthase and androgens in rat corpus cavernosum.

OBJECTIVE: To clarify the dependence of neural nitric oxide synthase mRNA (nNOSmRNA) and endothelial nitric oxide synthase mRNA (eNOSmRNA) on androgens (testosterone [T] and dihydrotestosterone [DHT]). METHODS: 160 male Sprague Dawley (SD) rats were divided into Groups A (56 rats, 5 weeks old), B (50 rats, 10 weeks old) and C (54 rats, 58 weeks old). Groups A, B and C were all subdivided respectively into five Subgroups. Subgroup 1: intact controls; Subgroup 2: castrated; Subgroup 3: castrated with testosterone undecanoate 25 mg/kg.mon-1, intramuscular injection, Subgroup 4: castrated with testosterone undecanoate 50 mg/kg.mon-1, intramuscular injection and Subgroup 5: treated with finasteride 4.5 mg/kg.day-1, orally. Four and ten weeks after treatments described above, one half of the rats were killed. Serum samples were taken for measurements of T, free testosterone (FT) and DHT by radioimmunoassay. Penile samples were treated with liquid nitrogen and then stored at -80 degrees C. nNOSmRNA and eNOSmRNA were detected by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) and Dot blot. RESULTS: There was no significant difference between Subgroup 1 and Subgroup 2 or Subgroup 5 in all Groups A, B and C. The expression of penile eNOSmRNA of Group A was significantly increased (4 weeks model) (P < 0.05) or increased (10 weeks model) (P > 0.05) in Subgroup 2 or 5 compared with those in Subgroup 1. There was no significant difference between Subgroup 1 and Subgroup 2 or Subgroup 5 of Group B in 4 weeks model (P > 0.05). There was an elevation when animals were castrated or treated with finasteride in the 10 weeks model. The expression of penile eNOSmRNA of Group C was significantly increased (10 weeks model) (P < 0.05) or increased (4 weeks model) in Subgroup 2 compared with those in Subgroup 1. The production of eNOSmRNA in Subgroup 5 was also increased (including 4- and 10-week models). When T was supplied for castration, the penile eNOSmRNA was decreased to some extent; the greater the dose of T given, the lower penile eNOSmRNA was observed. CONCLUSIONS: The expression of eNOSmRNA in SD rat penile tissue increases while T or DHT diminishes. Sometimes androgens modulate penile eNOSmRNA in opposite directions. There is no correlation between the expression of nNOSmRNA and androgens (including T and DHT). Androgens give rise to penile erection probably not via the NOS pathway.

Androgens↗
PubMed2000

[Study on the relationship between CD44v6, p53 gene mutation and ovarian carcinoma metastasis].

OBJECTIVE: To explore the relationship between CD44v6 expression, p53 gene mutation, cell ploidy and ovarian metastasis. METHODS: Eighty-five ovarian specimens (20 normal specimens, 20 benign tumors, 20 non-metastatic carcinomas and 25 metastatic carcinomas) were collected. Cell ploidy and the distribution of cell population in each stage of cell cycle were detected by flow cytometry. By using techniques such as reverse transcription-polymerase chain reaction, southern blot and image analysis, the quantitative and qualitative expression of CD44v6 were determined; the mutation of p53 gene in the ovarian specimens was also determined by polymerase chain reaction-single strand conformation polymorphism with silver staining. RESULTS: In the normal ovarian specimens, benign tumors, non-metastatic and metastatic carcinomas, the positive rates of CD44v6 expression and p53 gene mutation were 0%, 10%, 75%, 88% and 0%, 5%, 40%, 60%, respectively, both increased gradually. The mean dark density in the non-metastatic (3,820 +/- 289) and metastatic (10,132 +/- 1,521) groups was significantly different (P < 0.01). In the positive and negative CD44v6 ovarian carcinoma groups, the mean carcinoma cell percentage at the G2M stage was 5.90% and 5.06% (P > 0.05), mean aneuploidy carcinoma cell percentage was 57% and 50% (P > 0.05) respectively. In the mutated and non-mutated p53 gene groups, their mean cell population at the G2M stage was 11.15% and 5.85% (P < 0.05), mean aneuploidy carcinoma cell percentage was 74% and 36% (P < 0.05), respectively. CONCLUSIONS: The expression of CD44v6 is closely related to carcinoma metastasis. The relationship between CD44v6 expression, p53 gene mutation and carcinoma metastasis can be involved in the different mechanism. As compared to mutated p53 gene, CD44v6 appears to be more suitable as a metastatic marker.

Adult↗
PubMed2000

[Genistein exerts multiple suppressive effects on human breast carcinoma cells].

OBJECTIVE: To study the suppressive effects of genistein on progression of breast carcinoma. METHODS: In vitro cell culture, animal studies, zymography, Northern and Western blot were used in this study. RESULTS: Genistein inhibited in vitro invasion of MCF-7 and MDA-MB-231 cells. This inhibition was associated with down-regulation of MMP-9 and up-regulation of TIMP-1. These effects were also demonstrated in vivo. Genistein inhibited growth of the breast cancer cells transplanted in nude mice. The growth inhibitory effect was associated with increased tumor cell apoptosis, and up-regulated p21WAF1/CIP1 expression. Furthermore, genistein inhibited angiogenesis as shown by decreased vessel density and decreased production and release of VEGF and TGF-beta 1. CONCLUSION: Genistein exerts multiple suppressive effects on breast carcinoma. It may help halt its progression.

Animals↗
PubMed2000

[Fiberoptic ductoscopy for patients with intraductal papillary lesions].

OBJECTIVE: To investigate the clinical significance of fiberoptic ductoscopy in patients with intraductal papillary lesions. METHODS: Fiberoptic ductoscopy was applied to patients with nipple discharge. The characteristics of those with intraductal papillary lesion were analysed. RESULTS: 92 patients were found to have intraductal papillary lesions. 68 patients were revealed to have single papillomas and 21 multiple papilloma. Three patients were diagnosed with papillomatosis. A total of 114 lesions were observed. 29.8% of these lesions were located in the segmental duct. 43.9% lesions were located in the first branch of the segmental duct and 17.5% in the second branch. Only 7.9% and 0.9% lesions were located in the third and the fourth branch. The average distance from lacteous pore to papillary lesion was 2.7 cm. Fiberoptic ductoscopy did not find lesions in 5 patients. CONCLUSIONS: Fiberoptic ductoscopy can be used to diagnose and locate intraductal papillary lesions. It is an effective diagnostic method for nipple discharge.

Adult↗
PubMed2000

[The prevention of primary liver cancer by selenium in high risk populations].

OBJECTIVE: To study the preventive effects of selenium on primary liver cancer. METHODS: After screening of blood samples in 18,000 males from 20 to 65 years-old in Qidong, Jiangsu province (a high risk area for liver cancer), 2,065 cases of HBsAg positive, AFP negative and normal liver function (normal ALT values) were found. The subjects were randomly divided into two groups, based on their residence areas; 1,112 subjects (experimental group) received one tablet of sodium selenite (0.5 mg Se) every day and 953 subjects (control group) received one placebo tablet every day. RESULTS: During three years of intervention and follow up, the blood selenium concentration and glutathione peroxidase activity of the subjects in the experimental group were increased and had significant difference as compared with those of the control group (P < 0.01). At the same time, the prevalence rate of micronucleus cells in peripheral blood lymphocytes in the experimental group was significantly lower than that of the control group (P < 0.01), and the incidence of new liver cancer in the experimental group (3 057.55/10(6), 34 cases out of 1,112 subjects) was significantly lower than the control group (5 981.11/10(6); 57 cases out of 953 subjects) (P < 0.01). CONCLUSION: The results confirms that selenium supplementation in general populations lived in high risk is effective in the prevention of liver cancer and the using of selenium tablets is simple and feasible.

Adult↗
PubMed2000

[Morphological changes of mitochondria in apoptosis of esophageal carcinoma cells induced by As(2)O(3)].

OBJECTIVE: In order to make clear how As(2)O(3) targets the cells of esophageal carcinoma, the morphology of mitochondria and expression of bcl-2/bax were selected to study the SHEEC1 cell line during early apoptosis. METHODS: The esophageal carcinoma cell line SHEEC1 was treated by As(2)O(3) with concentrations of 1, 2 and 3 micromol/L for the periods of 2, 4, 6, 12 and 24 h. Annexin-V-Fluorescein and DNA histogram were used to detect the early apoptotic cells by flow cytometry. The morphologic changes of the apoptotic cells were examined by means of light and electron microscopy. Changes in mitochondria of living cells were detected with Rhodamin 123 fluorescent probe by fluorescent microscopy. The expression of bcl-2 and bax in floating cells were determined by immunohistochemical procedures. RESULTS: Typical apoptotic morphological changes were found in SHEEC1 at 24 h after As(2)O(3) treatment. Cells in the early stage of apoptosis were detected by Annexin-V labeled at 4 h. The ultrastructural alterations of mitochondria were found as following: within 4 h after administrating As(2)O(3), mitochondrial hyperplasia with small electron-dense materials in its matrix was the earliest manifestation of cell injury. At 6 h progressive mitochondrial swelling lead to balloon-like appearance and its outer membrane disrupted at 12 h. In all groups, down regulated expression of bcl-2 and over expression of bax were always found in damaged cells. CONCLUSION: In the SHEEC1 cell line morphological changes of mitochondria are the early events in apoptosis induced by As(2)O(3) and apoptosis is closely related to over expression of bax and down-regulating expression of bcl-2. It is possible that As(2)O(3) is a mitochondriotoxic anticancer agent for esophageal carcinoma.

Antineoplastic Agents↗
PubMed2000

[Lymphocyte subsets analysis and glycosylphosphatidylinositol determination in patients with PNH].

OBJECTIVE: Absolute number of lymphocyte subsets and the proportion of glycosylphosphatidylinositol (GPI)-deficient clones among T, B and NK cells were determined. METHODS: By using multicolor flow cytometry with two and three color labelled monoclonal antibodies, absolute number of lymphocyte subsets and the proportion of CD(48), CD(55), CD(59)-deficient T, B and NK cells were analyzed. RESULTS: Lymphocyte subsets were found abnormal in all patients, low absolute number of natural killer cells and B cells were obvious. In most patients, GPI-deficient T, B and NK cells were detectable. The proportion of GPI-deficient clones in T, B and NK cells were 78.7%, 53.4% and 30.5%, respectively. There was significant difference among T, B and NK cells (P < 0.01). In two continuous remission cases, no GPI-deficient clones were found in erythrocytes, but there were GPI-deficient T and B cells, and in a 3 year remission there were still GPI-deficient NK cells. CONCLUSIONS: In PNH, similar to other blood cells, lymphocytes also had GPI deficiency, and GPI-deficient T and B cells could exist for a long time. NK cells of PNH patients are the predominant, GPI-deficiency cells with a high frequency (93.3%) and high proportion (78.7%).

Adult↗