Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease closely related to metabolism， which is mainly characterized by abnormal lipid deposition in hepatocytes. In recent years， with the increasing prevalence of obesity and metabolic syndrome， NAFLD has become one of the most common chronic diseases in the world. The pathogenesis of NAFLD is complex and varied， involving the cross-regulation of multiple signaling pathways such as glucose-lipid metabolism， oxidative stress， and inflammation. The TLR4 signaling pathway plays a key role in the development and progression of NAFLD， and abnormal activation of this pathway accelerates the deterioration of NAFLD by promoting the release of pro-inflammatory cytokines， inducing oxidative stress， and exacerbating insulin resistance. Studies have shown that traditional Chinese medicine （TCM） can regulate the TLR4 signaling pathway to alleviate the symptoms and pathological features of NAFLD. The present review summarizes the experimental research progress in the TCM regulation of the TLR4 signaling pathway in treating NAFLD in the past 5 years， covering a wide range of TCM active ingredients （such as polysaccharides， terpenoids， alkaloids， flavonoids） and compound prescriptions. The active ingredients and compound prescriptions of TCM can effectively ameliorate lipid metabolism disorders， reduce insulin resistance， regulate intestinal flora， and inhibit inflammation and oxidative stress by regulating the TLR4 signaling pathway via multiple targets and pathways， thus slowing down the progression of NAFLD. Through in-depth analysis of the pathological mechanisms of NAFLD and exploration of the potential of TLR4 signaling pathway as a therapeutic target， we can provide theoretical support for the application of TCM in the treatment of NAFLD， as well as new perspectives and directions for future clinical research and new drug development， thereby promoting the innovation and development of therapeutic strategies for NAFLD.

OBJECTIVE: To compare the impact of different peroneus longus tendon (PLT) stump management techniques on ankle function following arthroscopic anterior cruciate ligament (ACL) reconstruction with autologous PLT grafts. METHODS: A retrospective analysis was conducted on 60 patients with ACL rupture who met the inclusion criteria between August 2020 and July 2024. All patients underwent arthroscopic ACL reconstruction using the autologous PLT grafts. Patients were assigned to group A [PLT stump sutured to peroneus brevis tendon (PBT), n=30] or group B (no stump intervention, n=30). The two groups showed no significant difference ( P>0.05) in baseline data, including gender, age, body mass index, injury mechanism, affected side, preoperative American Orthopaedic Foot and Ankle Society (AOFAS) score, ankle muscle strength, ankle range of motion, and arch-related angles. Postoperative outcomes were assessed using the AOFAS score, ankle muscle strength (eversion and first-ray plantar flexion), arch-related angles (medial/lateral longitudinal and anterior/posterior arch), ankle range of motion (eversion, inversion, dorsiflexion, plantarflexion), and limb symmetry index (LSI). Change values in muscle strength, arch-related angles, and range of motion from preoperative to 12 months postoperatively were calculated for intergroup comparison. RESULTS: Groups A and B had comparable PLT graft lengths and diameters ( P>0.05). All patients were followed up 13-16 months (mean, 14.5 months). Postoperative complications included 1 case of incision infection, 1 case of deep vein thrombosis, and 1 case of knee stiffness in group A, 1 case of knee stiffness in group B. There was no significant difference in the overall complication incidences between groups ( P>0.05). No significant difference was found in the AOFAS scores between different time points and between groups ( P>0.05). At 12 months after operation, neither group showed significant changes from preoperative baseline in ankle strength, range of motion, or arch-related angles, and there was no significant difference in these change values between groups ( P>0.05). There was no significant difference in LSI between the two groups at 6 or 12 months postoperatively ( P>0.05). CONCLUSION Both suturing and leaving the PLT stump untreated during arthroscopic ACL reconstruction provided comparable ankle outcomes and well-preserved foot and ankle function.
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Male ; Retrospective Studies ; Female ; Adult ; Anterior Cruciate Ligament Injuries/surgery* ; Tendons/transplantation* ; Range of Motion, Articular ; Arthroscopy/methods* ; Young Adult ; Treatment Outcome ; Muscle Strength ; Transplantation, Autologous ; Ankle Joint/surgery* ; Middle Aged ; Adolescent

In this comprehensive review, we delve into the evolution of drug delivery systems in reproductive medicine with a focus on the emerging role of exosomes, a class of extracellular vesicles. Exosomes offer unique advantages in overcoming these challenges due to their inherent biocompatibility, stability, and ability to facilitate targeted delivery. This review provides a detailed examination of exosome biogenesis and their function in cellular communication, setting the stage for understanding their potential as drug delivery vehicles. We explore the mechanisms through which exosomes can be loaded with small molecule drugs and the benefits they offer over synthetic nanoparticles. The review highlights groundbreaking case studies that illustrate the successful application of exosome-mediated drug delivery in reproductive health, including enhancing fertility treatments, supporting gamete and embryo development, and facilitating maternal-fetal communication. This study aims to provide a precise understanding of how exosomal drug delivery can revolutionize treatments for reproductive health disorders, paving the way for future therapeutic applications. Lastly, we touch upon the promising therapeutic implications of exosomal delivery for proteins and genes, offering a window into future treatments for reproductive health disorders.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective·To develop physiologically based pharmacokinetic(PBPK)models specifically designed for the Chinese population by utilizing the combination of clozapine and fluvoxamine as a case,and predict the drug-drug interaction(DDI)associated with the combination medication of clozapine,ultimately optimizing the dosage of clozapine.Methods·By obtaining the physicochemical parameters,absorption,distribution,metabolism,excretion(ADME)-related parameters,and physiologically relevant parameters of the Chinese population through literature and pharmacology-related databases,PBPK models for the clozapine and fluvoxamine were constructed by using PK-Sim? software.The models' accuracy was evaluated by comparing predicted values of the area under the curve(AUC)and peak concentration(Cmax)to observed data,using the mean percentage error(MPE)and mean absolute percentage error(MAPE)as evaluation indicators.The models were validated against real-world plasma drug concentration data.Additionally,combining the inhibitory effect of fluvoxamine on clozapine,models for the combination therapy of clozapine and fluvoxamine were developed to predict the pharmacokinetic changes of clozapine.The presence of clinically significant DDI was determined by using the 90%confidence interval of the AUC ratio(AUCR)or Cmax ratio(CmaxR)as evaluation metrics,with a non-effect boundary set at 80%?125%.The pharmacokinetic changes of clozapine upon co-administration with fluvoxamine based on PBPK models were quantified,and a dosage optimization for clozapine was developed.Results·The constructed model of clozapine and fluvoxamine was considered accurate if the absolute value of the MPE was≤10%and the MAPE was<25%during validation,indicating that the predicted concentration-time curves were accurate.The PBPK model for the co-administration of clozapine and fluvoxamine was able to accurately predict pharmacokinetic parameters if the ratio of predicted AUC to observed AUC was within 1.25.The prediction of PBPK model for the co-administration showed that the 90%confidence intervals for AUCR and CmaxR of the combination therapy of clozapine and fluvoxamine were not entirely within the ineffective effect boundary,indicating a clinically significant DDI when these two drugs were used concomitantly.Moreover,the dose optimization according to the PBPK models indicated that when subjects were co-administered with clozapine and fluvoxamine,reducing the dose of clozapine to 50%of the original dose could maintain the exposure levels of clozapine consistent with monotherapy.Conclusion·The established PBPK model can effectively simulate the impact of combination therapy on pharmacokinetic changes of clozapine,providing valuable insights for predicting potential DDI and optimizing dosage regimens.If clozapine needs to be co-administered with fluvoxamine during the treatment,clinicians should remain vigilant for clinically significant DDI and contemplate optimizing the dosage of clozapine accordingly.

Objective:To investigate the relationship between the outcome of skin injury and urinary arsenic methylation metabolism levels in people exposed to arsenic through drinking water.Methods:Using cluster sampling method, permanent residents from drinking-water-borne endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region were selected as survey subjects in 2004 (before water improvement). In 2017 (after water improvement), 74 survey subjects from 2004 were tracked and followed up. Urine samples were collected from survey subjects and high-performance liquid chromatography inductively coupled plasma mass spectrometry was used to detect the levels of arsenic methylation metabolites in urine. According to the "Diagnosis of Endemic Arsenic Poisoning" (WS/T 211-2015), the clinical grading (normal, suspicious, mild, moderate and severe) of skin injury of the survey subjects and the outcome of 2017 (improved, unchanged, aggravated) were assessed. A database was established and SPSS 25.0 software was used for statistical analysis.Results:The clinical grading ratios of skin injuries among survey subjects in 2004 and 2017 were compared, the differences were statistically significant (normal, suspicious, mild, moderate and severe: 38, 18, 4, 14 cases in 2004 and 27, 31, 3, 13 cases in 2017, χ 2 = 53.02, P < 0.001). Compared with 2004, in 2017, the levels of total arsenic (tAs), inorganic arsenic (iAs), monomethylarsenic (MMA), dimethylarsenic (DMA), percentage of inorganic arsenic (iAs%), and ratio of monomethylarsenic to dimethylarsenic (MMA/DMA) in the urine of survey subjects were low, and the differences were statistically significant ( Z = - 8.24, - 9.07, - 7.81, - 8.04, - 8.24, - 3.56, P < 0.001). The levels of dimethylarsenic percentage (DMA%), monomethylation rate (PMI) and dimethylation rate (SMI) were higher, and the differences were statistically significant ( Z = - 6.39, - 8.24, - 3.52, P < 0.001). In 2004, patients with different clinical grading of skin injuries had different outcomes in 2017 (χ 2 = 30.80, P < 0.001). There were statistically significant differences in tAs, iAs, MMA and DMA variation in urine among skin injury patients with different outcomes ( H = 10.62, 9.35, 8.80, 9.13, P < 0.05). Conclusions:Improving water can significantly reduce the levels of tAs, iAs, MMA, and DMA in the urine of arsenic exposed individuals. The outcome of skin injury in individuals exposed to arsenic through drinking water is related to the variation of urinary arsenic methylation metabolites tAs, iAs, MMA, and DMA.

Objective:To compare the short-term efficacy of laparoscopic sleeve gastrectomy (LSG) combined with sharp His angle reconstruction (LSG-His) versus traditional LSG.Methods:In this retrospective cohort study we collected clinical data of patients with obesity who had undergone LSG or LSG-His in the Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, from January to June 2022. After excluding patients with incomplete follow-up data and those with hiatal hernia, 83 obese patients, of which 39 who had undergone LSG (LSG group) and 44 who had undergone LSG-His (LSG-His group), were included in the study. The basic steps in LSG-His are the same as in conventional LSG. After continuous suturing of the gastric staple line, one stitch is placed between the proximal side of the gastric greater curvature staple line and the proximal side of the gastric fundus posterior wall with the left diaphragm, and another stitch between the right side of the gastric fundus and the esophagus, reconstructing the sharp His angle. Clinical data, postoperative complications, and follow-up data on weight loss and gastroesophageal reflux disease (GERD) symptoms 1-, 3-, 6-, and 12-months post-discharge were compared between the two groups. GERD symptoms were assessed using the Gastroesophageal Reflux Disease Questionnaire and Reflux Diagnostic Questionnaire.Results:There were no significant differences between the two groups in baseline characteristics, length of hospital stay, hospitalization costs, intraoperative bleeding, postoperative nausea and vomiting, dysphagia, or postoperative complications (all P>0.05). Compared with the LSG group, the LSG-His group had significantly longer operative times (92 [80, 100] minutes vs. 80 [70, 100] minutes, U=2.227, P=0.026), higher postoperative 24-hour pain scores (5.2±1.8 vs. 4.3±1.9, t=-2.065, P=0.041), and higher rates of morphine use (70.5% [31/44] vs. 46.2% [18/39], χ2=4.519, P=0.025). The incidence of new-onset GERD 12 months postoperatively was significantly lower in the LSG-His than the LSG group (10.7% [3/28] vs. 61.3% [19/31], χ2=14.00, P<0.001). According to changes in Gastroesophageal Reflux Disease Questionnaire and Reflux Diagnostic Questionnaire scores, the LSG-His group also had significantly lower rates of exacerbation of GERD (2/16 vs. 5/8, χ2=4.27, P=0.021) and higher rates of GERD remission (12/16 vs. 2/8, χ2=3.62, P=0.032) than did the LSG group. Additionally, excess weight loss rates were significantly higher in the LSG-His group at 3 months [(54.7± 18.7)% vs. (46.5±15.0)% , t=-2.166, P=0.033], 6 months [(73.8±24.7)% vs. (64.0±19.1)% , t=-2.018, P=0.047], and 12 months [(82.9±26.7)% vs. (72.2±19.3)%, t=-2.063, P=0.042] than in the LSG group. Conclusion:Compared with LSG, LSG-His is safe and feasible and achieves better short-term control of postoperative GERD and more effective weight loss. Further large-scale, long-term, prospective studies are needed to confirm the long-term efficacy of LSG-His.

Endemic fluorosis refers to an endemic disease caused by excessive intake of fluoride in the body of residents living in high fluoride environment due to natural or man-made pollution. Dental fluorosis and bone fluorosis are common symptoms of endemic fluorosis. In addition, long-term exposure to fluorine can cause damage to multiple systems such as the central nervous system, cardiovascular system, urinary system, ultimately leading to chronic lesions and functional impairments of multiple organs throughout the body. At present, endemic fluorosis remains one of the serious public health problems in China and even the world. Therefore, this article reviews the research progress on the damage of endemic fluorosis to the human body from both bone and non-bone systems, in order to provide reference for the continuous prevention and control of endemic fluorosis in the future.

Objective:To investigate the arsenic metabolism pattern and possible influencing factors in the population in drinking-water-borne endemic arsenic poisoning (drinking-water-borne arsenic poisoning for short) areas.Methods:In December 2004, a cluster sampling method was used to select arsenic poisoning population (arsenic poisoning group) and healthy population (control group) in drinking-water-borne arsenic poisoning area of Bayannur City, Inner Mongolia Autonomous Region as the survey subjects. A questionnaire survey was conducted. Arsenic content in drinking water at home of survey subjects, the levels of urinary arsenic and its metabolites, including [trivalent arsenic (As Ⅲ), inorganic arsenic (iAs), monomethylarsenic acid (pentavalent, MMA V), dimethylarsenic acid (pentavalent, DMA V), total arsenic (tAs), percentage of inorganic arsenic (iAs%), percentage of monomethylarsenic acid (MMA%), percentage of dimethylarsenic acid (DMA%), primary methylation index (PMI), secondary methylation index (SMI)] were tested using high performance liquid chromatography-inductively coupled plasma mass spectrometry; nail arsenic and nail selenium levels were tested using atomic fluorescence spectrometer. The influencing factors of arsenic metabolism pattern were analyzed by multiple linear regression. Results:A total of 536 survey subjects were included, including 155 individuals in the arsenic poisoning group and 381 in the control group. The water arsenic level ranged from 0.0 to 825.7 μg/L. Compared with the control group, there was no significant difference in the distribution of gender, education level and dental fluorosis in the arsenic poisoning group ( P > 0.05), but there were significant differences in the distribution of age, marital status, smoking, drinking and water arsenic ( P < 0.05). Compared with the control group, the levels of urinary As Ⅲ, iAs, MMA V, DMA V, tAs, MMA%, MMA/DMA and nail arsenic in the arsenic poisoning group were higher ( P < 0.05), while the levels of urinary DMA%, SMI and nail selenium were lower ( P < 0.05); but there was no statistically significant difference in the levels of urinary iAs% and PMI ( P > 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary As Ⅲ (β = - 19.82, - 23.83, 0.61, 0.21, 7.26, 2.98, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary tAs (β = 3.18, 3.25, 1.31, 15.59, P < 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary iAs (β = - 20.47, - 25.90, 0.64, 0.25, 7.87, 3.11, P < 0.05). Age, gender, education level, water arsenic and nail arsenic were the influencing factors of urinary MMA V (β = 0.52, - 17.07, - 21.84, 0.22, 2.77, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary DMA V (β = 2.35, 2.47, 0.85, 9.22, P < 0.05). Conclusions:Compared with healthy individuals, there are differences in arsenic metabolism pattern among individuals with drinking-water-borne arsenic poisoning. Age, gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic may be influencing factors of different arsenic metabolism patterns.