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Human Umbilical Cord Mesenchymal Stem Cells in Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD) Therapy: Mechanisms, Clinical Efficacy, and Future Perspectives.

There is currently no approved drug treatment for metabolic dysfunction-related fatty liver disease (MAFLD). Umbilical cord-derived mesenchymal stem cells (UC-MSCs) show therapeutic potential, but their mechanism of action is remains incompletely understood. Different from previous reviews that focused on a single pathway, this article presents three important contributions: First, it constructs an integrated "multi-target synergy network" model, clarifying how UC-MSCs coordinate and regulate the inflammatory, metabolic and fibrotic processes through the interactions between the AMPK/mTOR, Nrf2/HO-1 and TGF-β/Smad pathways; Second, it systematically assesses recent clinical trials (2022-2025), identifying several unaddressed barriers to transformation, including the lack of histological endpoint indicators, batch-to-batch differences, and the absence of dose exploration studies; Third, we integrate the latest developments from 2024 to 2025, particularly mitochondrial transfer (mediated by tunnel nanotubes and accompanied by quantitative efficacy data) and exosome circular RNA networks [Formula: see text], which have not been covered in previous reviews. Based on the above analysis, we also propose specific suggestions for standardized GMP production, mandatory genomic stability testing, and long-term safety registration. This review provides a comprehensive analysis of elaborates on the treatment of MAFLD with UC-MSCs from a mechanistic and translational perspective, based on the extensive updates of relevant literature.

Humans↗

Problems in diagnosis and surgical management of clinical N1 non-small cell lung cancer.

BACKGROUND: Clinical diagnosis of the nodal status is a significant factor in determining the treatment and predicting the prognosis in lung cancer patients. A patient with clinical N1 (cN1) disease is usually considered to be a candidate for surgical intervention in the present staging system in non-small cell lung cancer (NSCLC). However, cN1 disease is a subset for which the method of treatment and surgical results are variable, simply because both upstaging and downstaging can occur. We evaluated the surgical and pathologic results of cN1 NSCLC patients to reveal the problems in diagnosis and surgical management for this subset. METHODS: From January 1998 to March 2003, 1,606 patients underwent thoracotomy for primary lung cancer at the National Cancer Center Hospital. Among them, the subjects for this study were 168 (10.5%) NSCLC patients who were clinically diagnosed as having N1 disease and underwent surgery without induction therapy. RESULTS: The tumor cell types of these 168 cN1 NSCLC patients were adenocarcinoma in 73 (44%) and squamous cell carcinoma in 79 (47%). Pneumonectomy was performed in 26% (n = 43) patients, bilobectomy in 15% (n = 25), and exploratory thoracotomy in 11% (n = 19). Of 19 exploratory thoracotomy cases, 10 cases were due to pleural dissemination. The pathologic nodal status of the 135 patients who underwent pulmonary resection and mediastinal dissection was pN0, 19% (n = 25); pN1, 44% (n = 59); and pN2-3, 37% (n = 51). Of the 55 adenocarcinomas, 60% (n = 33) were revealed to be N2 disease on pathologic examination. There were no significant differences in the serum tumor markers between the pN1 and pN2 groups. Among the 25 patients who were downstaged postoperatively (cN1-pN0), 21 patients (84%) showed obstructive pneumonia in the lung. CONCLUSIONS: In the staging process of cN1 disease, it will be helpful to perform mediastinoscopy and thoracoscopy to avoid unnecessary thoracotomy especially in adenocarcinoma, even though mediastinal nodes and pleural dissemination were negative on computed tomography investigation. Since extensive pulmonary resection (bilobectomy or pneumonectomy) was required in 41% of the patients, preoperative detailed cardiopulmonary function tests should be mandatory to reduce surgical morbidity and mortality. On the other hand, when pneumonia due to airway obstruction by the tumor exists, false-positive hilar nodes can be expected.

Adenocarcinoma↗

Highly parallel microbial diagnostics using oligonucleotide microarrays.

Oligonucleotide microarrays are highly parallel hybridization platforms, allowing rapid and simultaneous identification of many different microorganisms and viruses in a single assay. In the past few years, researchers have been confronted with a dramatic increase in the number of studies reporting development and/or improvement of oligonucleotide microarrays for microbial diagnostics, but use of the technology in routine diagnostics is still constrained by a variety of factors. Careful development of microarray essentials (such as oligonucleotide probes, protocols for target preparation and hybridization, etc.) combined with extensive performance testing are thus mandatory requirements for the maturation of diagnostic microarrays from fancy technological gimmicks to robust and routinely applicable tools.

Bacteria↗

Defining, classifying, and placing incipient caries lesions in perspective.

A caries lesion begins with the introduction of a disease state, likely due to bacterial strains, in the oral cavity. If accompanied or followed by alterations to salivary flow, frequent periods of reduced salivary pH, or frequent intake of refined carbohydrates, the demineralization of tooth structure is likely to begin. The subsequent lesions first will be visible as white spot lesions, which if ignored, eventually will cavitate. Modern dentistry is capable of testing for the presence of caries lesions before cavitation, and it is suggested that routine testing should be mandatory for all patients who are at risk. If the disease is to be identified and treated before cavitation, it is desirable to adopt a new classification for the recognition and recording of caries lesions.

Dental Caries↗

Extensive preoperative testing is not necessary in morbidly obese patients undergoing gastric bypass.

Morbidly obese patients are considered at high risk for perioperative complications and often undergo extensive testing for preoperative clearance. We analyzed prospectively collected data from 193 patients undergoing weight loss surgery between November 2000 and November 2002. Preoperative chest x-ray examination, pulmonary function tests, noninvasive cardiac testing, and blood work were performed routinely. Preoperative testing identified abnormalities on eight chest x-ray films (4%) and 29 electrocardiograms (15%), none of which required preoperative intervention. Spirometry was abnormal in 41 patients (21%); logistic regression identified preexisting asthma as predictive of obstructive physiology (odds ratio [OR] 3.3; 95% confidence interval [CI] 1.2 to 8.9), and body mass index as predictive of restrictive physiology (OR 1.1; 95% CI 1.01 to 1.2). Arterial blood gases identified only one case of severe hypoxemia requiring intervention. Mild hypoxemia was associated with increasing age (OR 14.5; 95% CI 1.8 to 114). Echocardiography demonstrated four abnormalities (2%); previous history of cardiac disease was the only risk factor (OR 14.5; 95% CI 1.8 to 114). Complete blood count did not identify 84% and 50% of the patients with iron (n=31) and vitamin B(12) (n=12) deficiencies, respectively. Age, body mass index, and history of asthma were associated with abnormal pulmonary function tests and previous cardiac disease with abnormal cardiac testing. These tests are not mandatory as a routine preoperative evaluation and can be used selectively on the basis of medical history.

Adult↗

Noninvasive assessment of prostatic obstruction in elderly men with lower urinary tract symptoms associated with benign prostatic hyperplasia.

OBJECTIVES: To investigate what combination of easily available parameters allows the noninvasive prediction of infravesical obstruction in optimal agreement with urodynamic classification. Urodynamically, men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia are classified as nonobstructed or obstructed. METHODS: Mandatory and recommended tests were performed in 160 consecutive men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. The classification of the International Continence Society, the group-specific urethral resistance factor, and Schäfer's obstruction grade were estimated from urodynamic studies. The frequency-volume charts were analyzed. A separate group of 173 consecutive men was used for validation. RESULTS: The formula, prostate volume (in cubic centimeters) - 3 x maximal urinary free flow rate (in milliliters per second) - 0.2 x mean voided volume (in milliliters; as estimated from frequency-volume charts), was optimal in the classification compared with the urodynamic classification. Extension of this formula to more than three parameters did not result in better selection. As estimated from receiver operating characteristic curves, the accuracy of the formula appeared to be good. The method of quantifying urethral resistance minimally affected the classification that resulted from the combination. From the results, a diagram was created presenting the probability of an individual to have infravesical obstruction. The validation results were satisfactory. CONCLUSIONS: The prediction of the probability of a man with lower urinary tract symptoms suggestive of benign prostatic hyperplasia to have infravesical obstruction can be deduced from a diagram based on a formula composed of three readily available parameters: prostate volume, maximal urinary free flow rate, and mean voided volume.

Aged↗

High incidence of hepatitis B infections among chronic hepatitis cases of unknown aetiology.

BACKGROUND/AIMS: In approximately 5% of chronic liver disease cases, no aetiology can be identified. We selected sera from 50 patients with chronic hepatitis of unknown aetiology who were enrolled in this follow-up study whose aim is to gain insight into the possible role of viruses and to define potential clinical outcomes. METHODS: Patients' sera were screened with highly sensitive polymerase chain reaction assays for hepatitis B (HBV), C, D, and G viruses and TT virus. Sera were also retested for antibodies against the core antigen of HBV. RESULTS: Surprisingly, HBV DNA was detected in both serum and liver in 15/50 (30%) patients. Immunostaining for HBV antigens on biopsies from patients positive for HBV DNA showed HBcAg and/or HBsAg expression at low levels in 9/15 samples. Eleven of the fifteen patients were anti-HBc positive. With one exception, all patients carried HBV genomes at low levels (10(4) copies/ml or less). Histological signs of chronic liver disease were observed in all patients. CONCLUSION: Unrecognised HBV infections may account for a high proportion of chronic hepatitis cases of unknown aetiology. Improved HBV detection tests, which appear mandatory for the diagnosis and management of non-A non-E hepatitis as well as for improved safety of transfusions and transplantations are needed.

Adult↗

Tuberculosis control in the New York State Department of Correctional Services: a case management approach.

In the New York State Department of Correctional Services (DOCS), the incidence of tuberculosis (TB) increased from 43 per 100,000 persons in 1985 to 225 per 100,000 in 1991. To combat this increase in cases, the NYSDOCS enhanced its collaborative efforts with the New York State Department of Health and the Division of Parole, developing a comprehensive TB control program. This control program focuses on prevention and containment of disease. Policies and directives were developed on the basis of epidemiologic principles, which include surveillance and detection. To assist the NYSDOCS in the implementation of the TB control program statewide, a team of infection control nurses was established in July 1992. A case management approach was used, and TB registry was developed. Each case of active and suspected TB was monitored closely to ensure appropriate containment, identification, and treatment measures. Transfers within the state system also were monitored to promote continuity. Discharge planning coordination with the DOCS, Division of Parole, and Department of Health is facilitated by the infection control nurses. Directly observed preventive therapy and directly observed therapy is used for inmates. Staff and inmates are provided education that addresses mandatory annual skin testing, diagnosis, containment procedures, disease process, and treatment modes. Implementation of this comprehensive TB control program in NYSDOCS has strongly contributed to reducing the incidence of TB. In 1997, the incidence rate was 61 TB cases per 100,000 persons--a 73% decrease since 1991. The conversion rate for staff and inmates has steadily declined since 1993. No new outbreaks have occurred in NYSDOCS since 1993.

Case Management↗

Effect of head-out water immersion on cardiorespiratory response to dynamic exercise.

Head-out water immersion is known to produce several cardiopulmonary adjustments at rest due to a cephalad shift in blood volume. The purpose of this study was to determine the effect of head-out water immersion on the cardiorespiratory response to graded dynamic exercise. Nineteen healthy middle-aged men performed upright cycling exercise at 40, 60 and 80% of maximal oxygen consumption on land and in water (31.0 +/- 1.0 degrees C) to the shoulders. Cardiac output (measured by the carbon dioxide rebreathing technique) was significantly greater in water at 40 and 80% maximal oxygen consumption. Stroke volume was significantly elevated at all stages of exercise. Heart rate did not differ significantly at 40 and 60% maximal oxygen consumption but was significantly lower in water at 80% maximal oxygen consumption. Total ventilation did not differ significantly in water and on land at any stage of exercise. The results suggest that the central redistribution of blood volume with head-out water immersion leads to an increase in stroke volume. Because there is not a proportional decrease in heart rate with the elevated stroke volume, cardiac output is regulated at a higher level during upright exercise in water compared with that on land. In conclusion, there are serious limitations of available, prerecorded rhythm data bases for designing and testing of automatic external defibrillators. Performance can be adequately assessed only by extensive clinical tests, which seem mandatory for this new and important type of defibrillator.

Adult↗

Experimental atrioventricular bioprosthetic valve insertion: a simple and successful technique.

Animal testing has become mandatory for the development of new prosthetic heart valves. It is very expensive. Low mortality and morbidity are essential in controlling costs. A simple technique for atrioventricular valve replacement in dogs and sheep that includes normothermic cardiopulmonary bypass, the maintenance of a beating heart and the avoidance of excision of the natural valve is described. Results have been excellent.

Animals↗

Primary ciliary dyskinesia: age at diagnosis and symptom history.

UNLABELLED: Age at diagnosis and the symptom history of children with primary ciliary dyskinesia (PCD) are described by reviewing the case notes in the paediatric PCD clinic. Mean age at diagnosis was 4.4 y despite a history of neonatal respiratory distress in 37/55 cases, situs inversus in 38/55 cases and early onset troublesome rhinitis in 42/55. CONCLUSION: Diagnosis of PCD is often delayed despite the presence of typical symptoms early in life. The key clinical features of unexplained neonatal respiratory distress, early onset rhinitis, situs inversus and a productive cough are highlighted, which, especially when occurring in combination, makes early referral for specific testing for PCD mandatory.

Adolescent↗

Pitfalls in the determination of common analytes in the critically ill.

In the critically ill, the pre-analytical aspects of blood gas analysis still require attention from the clinician. Sampling and transport remain critical factors. Use of drugs may create analytical interferences for common analytes like glucose and protein. Icterus may falsely reduce creatinine and albumin values. Changes in the serum or plasma matrix (reduction of protein, increased covolume of solutes, ...) may furthermore cause important effects on the distribution of electrolytes. Enzyme activity measurements may be erroneous due to lack of essential oligoelements or reducing substances. Immunoassays may suffer from interferences caused by auto-antibodies. In case of hemolysis, a careful interpretation of test results is mandatory.

Autoantibodies↗

The consequences of administering blood pretested for HBs Ag by third generation techniques: a progress report.

Elimination of commercial blood, mandatory HBs Ag testing by third generation techniques, and detection and interdiction of incriminated blood donors have all contributed to a dramatic 63 per cent reduction in the estimated number of cases of transfusion-associated hepatitis from 424 in 1970 to 158 in 1973 and an even more dramatic drop in fatalities from 55 to 1970 to 10 in 1973.

Blood Donors↗

The value of symptom score, quality of life score, maximal urinary flow rate, residual volume and prostate size for the diagnosis of obstructive benign prostatic hyperplasia: a urodynamic analysis.

PURPOSE: We investigated which linear combination of scores for symptoms, quality of life, maximum urinary flow rate, residual volume and prostate size best discriminated men with prostatism who do and do not have obstruction. MATERIALS AND METHODS: Mandatory and recommended tests were performed in 196 men older than 50 years with prostatism. Schäfer's obstruction grade was estimated by urodynamic studies. Relative residual volume was defined as residual volume divided by cystometric capacity (times 100%). Correlation coefficients among the different parameters were estimated. Obstruction grade was correlated with linear weighted combinations of the parameters. RESULTS: Of the men 79% appeared to have obstruction. The formula, prostate size (cm.3) -3 x maximum urinary flow rate (ml. per second) + 1/4 of relative residual volume (%), correlated almost maximally with obstruction grade. Including quality of life score or symptom score in this expression had a negative outcome on the correlation. Calculation of this expression resulted in the bladder outlet obstruction number. In more than 50% of the men the bladder outlet obstruction number was greater than -2 and more than 90% had obstruction. In 25% of all men the bladder outlet obstruction number was greater than 13 and more than 95% had obstruction. CONCLUSIONS: Bladder outlet obstruction number may be calculated with an easy to use expression composed of prostate size, maximum urinary flow and relative residual volume. In 50% of the men with prostatism bladder outlet obstruction number will diagnose obstruction with a reliability of more than 90%.

Aged↗

HIV precautions for prevention in the workplace.

The concern over transmission of blood-borne disease from health care workers to patients has become a topic of increasing concern. The Human Immunodeficiency Virus (HIV) is one of these diseases. Mandatory HIV antibody testing of all patients and health care workers is currently under consideration with no solution immediately on the horizon. Orthopaedic health care workers are often involved in emergent care of trauma victims without the benefit of knowing the HIV status of these patients. Therefore, the only solution is to employ meticulous barrier techniques to prevent transmission of diseases such as HIV infection. Precautions for orthopaedic nurses are discussed in an effort to provide guidelines for prevention of transmission of disease.

Centers for Disease Control and Prevention, U.S.↗

Impact of fixative on recovery of mRNA from paraffin-embedded tissue.

Due to the evolution of advanced tissue-analysis tools, such as proteomics and functional and structural genomics, the demands for handling and preserving samples are changing. For gene expression analysis, the presence of intact and extractable messenger RNA in the test material is mandatory. To find an optimal fixative for tissues aimed for such analyses, we evaluated the morphology-, protein antigen-, and RNA-maintaining abilities of 2 precipitating tissue fixatives, methanol-acetone and Carnoy's. Both fixatives preserved the morphology and protein epitopes of tissues and allowed extraction of total RNA that was of significantly higher quality than RNA extracted from formalin-fixed tissue. Carnoy's fixative performed better than methanol-acetone in maintaining the integrity of RNA, especially when the fixed, paraffin-embedded tissue blocks were stored at room temperature for more than 3 months. Total RNA extracted from epithelial cells microdissected from Carnoy's-fixed tissue samples contained intact template for up to a 977-base pair (bp) amplicon for beta-actin. Because of the emerging role of gene expression analyses in research, and in clinical work in the near future, an RNA-preserving fixative should replace formalin as the primary human tissue fixative. According to our data, Carnoy's fixative is an excellent candidate for a new primary fixing reagent for human tissue samples.

Acetic Acid↗

Estimating lung mechanics of dogs with unilateral lung injury.

Extended least-squares algorithms using transpulmonary pressure and airway flow data from ventilatory waveforms were studied for their ability to track parameters of one- and two-compartment models of lung mechanics. A recursive extended least-squares algorithm with discounted measures estimated parameters of discrete-time models during synchronized intermittent mandatory ventilation. In tests on seven dogs developing oleic acid-induced unilateral hemorrhagic pulmonary edema, the one-compartment estimator responded rapidly and appropriately to changes in mechanics: compliance fell to 0.55 +/- 0.15 of its initial value and resistance rose by a factor of 1.8 +/- 0.5 in 3 h following injection of oleic acid. One-compartment parameter estimates revealed a difference between the airway resistance of inspiration and expiration. Two-compartment estimates were seldom physiologically plausible. The difference between inspiratory and expiratory resistance may have caused the two-compartment estimator to fail when applied to data from the entire respiratory cycle; when only expiratory data were used for estimation, the two-compartment estimates were meaningful. These estimates demonstrated increasing lung inhomogeneity after oleic acid was injected; at the end of 3 h, the ratio of the time constants of the two compartments ranged from 5 to 20 in six of the seven dogs. We conclude that the one- and two-compartment estimates may be combined to provide a meaningful assessment of lung mechanics.

Animals↗

Residual risk of transfusion-transmitted human immunodeficiency virus, hepatitis C virus, and hepatitis B virus infections in Italy.

BACKGROUND: Estimating the risk of transfusion-transmitted infections (TTIs) is essential for monitoring blood safety. The residual risk of TTI was estimated for nearly 90 percent of the blood supply in Italy. STUDY DESIGN AND METHODS: Data were analyzed from 1,079,281 repeat donors, corresponding to 5,361,000 donations made in blood transfusion centers throughout Italy in the period 1999 through 2001. The residual risk of transfusion-transmitted human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) infections was estimated with the incidence rate-window period model. The denominator for the incidence rate (i.e., the number of person-years at risk) was estimated on a sample of 5850 donors. RESULTS: The risk of an infectious donation entering the blood supply, per 1 million donations, was 1.91 (probable range, 0.52-3.32) for HIV, 16.74 (9.57-24.01) for HCV, and 69.16 (43.12-102.70) for total HBV (adjusted for vaccination and hepatitis B surface antigen transience). CONCLUSION: In Italy, the estimated residual risk of TTI is apparently low, particularly for HIV infection. Although the estimated risks are higher for HCV and HBV, the introduction of mandatory viral detection tests for HCV in 2002 should account for an 80 percent reduction in the HCV risk. Moreover, the ongoing HBV vaccination program will contribute to reducing the risk of transfusion-transmitted HBV.

AIDS Serodiagnosis↗