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.

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 study the role of special microbial communities in the development of periodontitis in type 2 diabetes melli-tus(T2DM)patients.Methods:40 subjects aged 20-70 years were included and divided into 3 groups:moderate to severe periodon-titis with T2DM(SP.T2DM,n=15),moderate to severe periodontitis group(SP,n=15)and normal healthy group(N,n=10).The basic information,periodontal clinical indicators and blood sugar of the subjects were recorded.Subgingival plaque samples were col-lected,DNA samples of the plaque were extracted,and sequenced by Illumina NovaSeq6000 platform.The microbial diversity,eco-logical characteristics and functions of the plaque were analyzed by Uparse,SPSS and other softwares.Results:481 species in 22 phyla,30 classes,73 orders,129 families and 265 genera were obtained from the samples.Beta polymorphism analysis showed that the species composition of CP.T2DM group and CP group was similar.Alpha polymorphism analysis showed that the species richness and evenness in CP.T2DM group and CP group were higher than those in N group(P＜0.01).Venn diagram analysis showed that the species richness of the plaque in CP.T2DM group was the highest,followed by CP group and the lowest in N group.At the genus lev-el,Klebsiella and Bifidobacterium in CP.T2DM group were larger than those in CP group and N group(P＜0.05),and between group CP and N,P＞0.05.At the species level,the Capnocytophaga leadbetteri in CP.T2DM group was higher than that in CP group and N group(P＜0.05),between group CP and N,P＞0.05;There were some differences in the microbial community structure of subgingival plaque among the 3 groups.The species richness of subgingival flora in patients with CP and T2DM was higher than that in patients with CP and healthy people.Conclusion:The increase of Klebsiella,Bifidobacterium and Capnocytophaga leadbetter in subgingival flora of patients with moderate and severe periodontitis may be related to the development of T2DM.

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.

BACKGROUND:Platelet-rich fibrin(PRF)is a second generation platelet concentrate with the advantages of simple operation,no anticoagulant,and high bioactivity,which has been applied in the fields of trauma repair,bone defect repair,and tendon soft tissue repair,and has been proved to have a certain tissue repair-promoting effect. OBJECTIVE:To study the repair effect of PRF on articular cartilage tissue in rats with knee osteoarthritis. METHODS:Thirty-six Sprague-Dawley rats were randomly divided into normal group,model group,and PRF group,with 12 rats in each group.Rats in the normal group did not undergo any treatment.In the model group,animal models of knee osteoarthritis were prepared and rat models were then given physiological saline into the joint cavity once a week after surgery.Rat models of knee osteoarthritis were also prepared in the PRF group,and autologous PRF was injected into the joint cavity once a week after surgery.After 5 weeks of continuous treatment,tissue samples were taken.Hematoxylin-eosin staining was used to observe the morphology of cartilage tissue.Tunel staining was used to detect chondrocyte apoptosis,ELISA was used to detect inflammatory factor levels.Western blot and RT-PCR were used to detect Bcl-2,Bax,and Caspase-3 expression in protein and mRNA levels,respectively. RESULTS AND CONCLUSION:The model group had severe cartilage tissue damage,while the PRF group had significantly improved cartilage tissue morphology compared with the model group.The model group had more apoptotic chondrocytes.Compared with the model group,the mean absorbance of Tunel positive staining in the PRF group significantly decreased(P<0.01).The levels of interleukin-1β,interleukin-6 and tumor necrosis factor-α were significantly increased in the model group and PRF group compared with the normal group(P<0.01)and were significantly decreased in the PRF group compared with the model group(P<0.01).The relative expressions of Bax and Caspase-3 at protein and mRNA levels were significantly increased in the model group and PRF group compared with the normal group(P<0.01),while the relative expressions of Bcl-2 at protein and mRNA were significantly decreased(P<0.01).Compared with the model group,the relative expression of Bax and Caspase-3 at protein and mRNA levels were significantly decreased in the PRF group(P<0.01),while the relative expressions of Bcl-2 at protein and mRNA levels were significantly increased(P<0.01).To conclude,PRF can inhibit chondrocyte apoptosis by inhibiting the expression of pro-inflammatory factors,thereby promoting cartilage tissue repair in knee osteoarthritis rats.

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.