ObjectiveTo investigate the mechanism of action of modified Chaihu Shugan Powder in the treatment of abnormal gallbladder relaxation in gallbladder cholesterol stone （CS） with liver depression syndrome， and to provide a basis for clinical medication. MethodsMice were given a high-fat lithogenic diet combined with chronic unpredictable mild stress （CUMS） to establish a model of CS. A total of 45 male C57BL/6 mice were randomly divided into blank group （6 mice fed a normal diet） and CS group （39 mice fed a high-fat lithogenic diet）. After CS modeling， the CS group was further randomly divided into four subgroups of CS group， CS liver depression group， traditional Chinese medicine group （treated with modified Chaihu Shugan Powder）， and Western medicine group （treated with ursodeoxycholic acid）， with 9 mice in each group. All subgroups were fed with the high-fat lithogenic diet， and all mice except those in the CS group were given 21 days of CUMS for modeling. Samples were collected after intervention. The serum levels of cholecystokinin （CCK）， liver function parameters， and blood lipid profiles were measured； HE staining was performed for liver and gallbladder tissue； qPCR and Western blot were used to measure the mRNA and protein expression levels of G protein-coupled bile acid receptor 1 （TGR5） and glucagon-likepeptide-1/2 （GLP-1/2） in the intestine and TGR5 and glucagon-like peptide-2 receptor （GLP-2R） in gallbladder； metabolomics methods were used to determine bile acid composition in intestinal contents. The independent-samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Games-Howell method was used for further comparison between two groups. ResultsCompared with the blank group， the CS group showed significant gallstone formation， bile turbidity， hepatic steatosis， abnormal gallbladder wall structure， and significant increases in anxiety- and depression-like behaviors based on behavioral tests； significant increases in the level of total cholesterol in bile and the serum levels of alanine aminotransferase， aspartate aminotransferase， and low-density lipoprotein and significant reductions in the level of total bile acid （TBA） in bile and the serum levels of CCK and high-density lipoprotein （HDL） （all P<0.05）； significant increases in the mRNA expression levels of GLP-1/2 and TGR5 in the intestine and the protein expression levels of GLP-2R and TGR5 in the gallbladder and significant reductions in the mRNA expression levels of GLP-2R and TGR5 in the gallbladder （all P<0.05）； significant changes in multiple bile acid components in intestinal contents （all P<0.05）. Compared with the CS group， the CS liver depression group had further aggravation of pathological and behavioral manifestations， changes in bile acid composition， significant increases in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine， and significant increases in the protein and mRNA expression levels of TGR5 and GLP-2R in the gallbladder （all P<0.01）. Compared with the CS liver depression group， both treatment groups had an improvement in gallbladder morphology， alleviation of stones and liver injury， and recovery of liver function and blood lipid levels， as well as significant reductions in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder （all P<0.05）； the traditional Chinese medicine group showed significant increases in glycodeoxycholic acid （GDCA）， tauro-α-muricholic acid （T-α-MCA）， and taurochenodeoxycholic acid （TCDCA） （all P<0.05）， while the Western medicine group showed significant increases in taurohyodeoxycholic acid， T-α-MCA， TCDCA， GDCA， and glycoursodeoxycholic acid （all P<0.05）. Compared with the Western medicine group， the traditional Chinese medicine group had significantly greater behavioral improvements， significantly higher levels of TBA in bile and serum HDL （both P<0.01）， significant reductions in the protein expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder， and a significant reduction in the mRNA expression level of TGR5 in the intestine （all P<0.01）， as well as a significant increase in tauroursodeoxycholic acid and significant reductions in glycoursodeoxycholic acid， taurohyodeoxycholic acid， TCDCA， and taurolithocholic acid （all P<0.05）. ConclusionModified Chaihu Shugan Powder can improve liver function and abnormal gallbladder relaxation in CS with liver depression syndrome by regulating the bile acid-TGR5 axis， thereby exerting the therapeutic effect of soothing the liver， resolving depression， moving Qi， and promoting bile flow.

OBJECTIVE To investigate the ameliorative effect and mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles（Eh-ENVs） on acetaminophen （APAP）-induced liver injury based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H：quinone oxidoreductase 1 （NQO1） pathway. METHODS The safety of Eh-ENVs was evaluated by examining their effects on the viability of RAW264.7 and AML12 cells， as well as serum liver and kidney function indicators and histopathology of liver， lung， and other tissues in normal mice. A lipopolysaccharide （1 μg/mL）-induced RAW264.7 cell inflammation model was constructed to investigate the effects of 10 and 20 μg/mL Eh-ENVs on the mRNA expression of inflammatory factors and reactive oxygen species （ROS） level in model cells， and the uptake efficiency of Eh-ENVs by RAW264.7 cells was also examined. An APAP-induced liver injury mouse model was established to investigate the effects of 4 mg/kg Eh-ENVs on serum liver function indicators， liver histopathology， mRNA expression of inflammatory factors， malondialdehyde （MDA） level， superoxide dismutase （SOD） level， and mRNA and protein expressions related to the Nrf2/HO-1/NQO1 pathway in liver tissue of model mice. RESULTS In vitro results showed that Eh-ENVs had no inhibitory effect on the proliferation of RAW264.7 and AML12 cells；Eh-ENVs could be efficiently taken up by RAW264.7 cells and significantly reduced the mRNA expression of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and ROS level in cells （ P ＜0.05）. In vivo results showed that 4 mg/kg Eh-ENVs had no obvious toxic side effects on normal mice，could significantly decrease the serum alanine transaminase （ALT） and aspartate transaminase （AST） levels in model mice （ P ＜0.05），upregulated/increased the mRNA expressions of IL-10， as well as the mRNA and protein expressions of Nrf2， HO-1， and NQO1， and SOD level in liver tissue （ P ＜0.05）， and down-regulated/decreased the mRNA expression of TNF-α， IL-1β and MDA level in liver tissue （ P ＜0.05）. CONCLUSIONS Eh-ENVs may activate the Nrf2/HO-1/NQO1 pathway to inhibit inflammatory response and alleviate oxidative stress， thereby improving APAP-induced liver injury.

Objective To investigate the exposure-response relationships and lag effects between air pollutants (PM_2.5, PM₁₀, O₃, and NO₂) and mortality in Jiading District, Shanghai, and to provide a scientific basis for the formulation of environmental health policies. Methods Using an individual-level time-stratified case-crossover design, conditional logistic regression models in conjunction with a distributed lag nonlinear model (DLNM) were employed to analyze the exposure-response relationship and temporal lag patterns of ambient air pollution on resident mortality in Jiading District (1994–2024). Results A total of 59 048 death cases were collected, including 18,701 deaths from cardiovascular diseases and 11 731 deaths from respiratory diseases. PM_2.5 and NO₂ had a significant impact on all-cause mortality, cardiovascular disease mortality, and respiratory disease mortality, with the most significant effects observed within a lag of 0–3 days. PM₁₀ also had some impact on these three types of mortality, but its effect was generally weaker than that of PM_2.5 and NO₂. The exposure-response curves showed that the risk of death increased rapidly with increasing concentrations of PM_2.5 and PM₁₀, while the effect of NO₂ plateaued at higher levels. No significant differences were found across age or gender subgroups. Conclusion Short-term exposure to PM_2.5, PM₁₀, and NO₂ significantly increases all-cause mortality risk in Jiading District, with effects persisting up to 7 days, highlighting the need for enhanced air pollution control measures, particularly targeting fine particulate matter.

Objective To analyze the underestimated influencing factors of ductal carcinoma in situ(DCIS)detected by ultrasound-guided fine needle aspiration cytology(US-FNAC),and to construct and validate the nomogram prediction model.Methods A total of 105 patients with DCIS diagnosed by US-FNAC in Yixing Hospital of Traditional Chinese Medicine from January 2020 to June 2023 were retrospectively selected.All patients were female and aged 40-76 years.According to postoperative pathological results,they were assigned to underestimated group(n=27)and non-underestimated group(n=78).The clinical data of the patients were collected to analyze the influencing factors of the underestimation of DCIS,and a nomogram prediction model was constructed.The receiver operating characteristic curve(ROC)was drawn,and the area under the curve(AUC)was used to analyze the predictive efficacy of the prediction model for the underestimated risk of DCIS before operation.Results Univariate analysis showed that the proportions of palpable masses,tumor size>2 cm,microcalcification,and breast imaging reporting and data system(BI-RADS)4B-5 in the underestimated group were higher than those in the non-underestimated group(P<0.05).Binary logistic regression analysis showed that tumor size[(odds ratio,OR)=4.453,95%(confidence interval,C I):1.890-10.486],microcalcification(OR=3.079,95%CI:1.650-5.742),BI-RADS classification(OR=5.211,95%CI:2.528-10.740)were the independent risk factors for preoperative underestimation of DCIS(P<0.05).Internal validation of the nomogram prediction model based on the above factors showed that the C-index was 0.865(95%CI:0.785-0.952),and the correction curve for predicting the underestimation of DCIS was close to the ideal curve(P>0.05).ROC curve showed that the nomogram model had a sensitivity of 87.90%,a specificity of 88.60%,and an AUC of 0.895(95%CI:0.823-0.966).Conclusion Tumor size,microcalcification and BI-RADS classification are independent risk factors for preoperative underestimation of DCIS.The nomogram prediction model based on these factors can better evaluate the risk of preoperative underestimation of DCIS.

Objective To explore the effects of the Otago Exercise Program(OEP)on activities of daily living,muscle strength,balance,and physical function in older adults with sarcopenia,to compare OEP with conventional exercise training,and to provide a basis for clinical rehabilitation programs for older adults with sarcopenia.Methods In this randomized controlled trial,120 older adults clinically diagnosed with sarcopenia were enrolled.The participants were randomly assigned to the OEP intervention group(experimental group)and the conventional exercise intervention group(control group),with 60 in each group.The experimental group underwent 12 weeks of OEP training,three times a week,with each session lasting 45 minutes.The control group underwent conventional exercise training following the same schedule.The Modified Barthel Index was used as the primary outcome measure to assess activities of daily living.Secondary outcome measures included muscle strength,gait stability,dynamic balance,and physical function status,evaluated using grip strength,6-meter walking speed,the Timed Up and Go Test(TUGT),and the Short Physical Performance Battery(SPPB).Results A total of 120 older adults with sarcopenia were included.The mean age of the participants was(80.17±8.48)years.Baseline data before treatment showed no statistically significant differences between the two groups.Both groups completed the treatment within 12 weeks without experiencing any adverse events.The baseline data for the experimental group were as follows,MBI at(67.00±22.76)points,hand grip strength at(15.29±4.94)kg,gait speed at(0.61±0.26)m/s,TUGT time at(15.05±6.74)s,and SPPB score at(6.17±1.40)points,while the corresponding post-intervention findings were as follows,(78.72±15.83)points,(17.67±5.83)kg,(0.77±0.28)m/s,(13.49±6.16)s,and(9.25±1.71)points,respectively.The experimental group showed improvements in all measures from baseline to post-intervention(P＜0.05 for all measures).As for the control group,the baseline data for the corresponding measures were as follows,(67.20±22.12)points,(15.00±5.35)kg,(0.58±0.23)m/s,(17.29±6.90)s,and(6.00±1.24)points,respectively.The post-intervention findings increased to(71.13±20.28)points,(15.47±5.72)kg,(0.64±0.28)m/s,(16.50±6.99)s,and(6.73±1.61)points,respectively,but the changes were not statistically significant(P＞0.05).Furthermore,an intergroup comparison of intervention effects(post-intervention minus preintervention)revealed significant differences in mean changes from baseline.The experimental group demonstrated improvements of(+11.72±6.32)points in modified Barthel Index,(+11.72±6.32)kg in grip strength,(+0.16±0.09)m/s in gait speed,(—1.56±1.32)s in TUGT time,and(—1.56±1.32)points in SPPB score.In contrast,the control group showed smaller changes of(+3.93±5.65)points,(+0.47±1.37)kg,(+0.06±0.07)m/s,(—0.79±1.54)s,and(+0.73±1.12)points,respectively(all P＜0.05).Intergroup comparisons revealed superior outcomes in the experimental group across all measures.Conclusion OEP significantly enhances activities of daily living,improves muscle strength,balance,and physical function in older adults,and is more effective than conventional rehabilitation exercise programs,making it suitable for extensive clinical application.

Objective To investigate the comprehensive intervention effects of transfer energy capacitive and resistive(TECAR)therapy combined with β-hydroxy-β-methylbutyrate(HMB)nutritional supplementation in older patients with sarcopenic obesity(SO).Methods We conducted a randomized controlled trial,enrolling 140 older patients who met the Asian diagnostic criteria for SO.Participants were randomly assigned to 4 groups,including a double-placebo group(Group A),TECAR+placebo group(Group B),sham TECAR+HMB group(Group C),and TECAR+HMB group(Group D),with 35 patients in each group.The intervention lasted 12 weeks.The primary outcome measure was the total score of the Short Physical Performance Battery(SPPB).Secondary outcome indicators included the modified Barthel Index(MBI),scores of the Mini Nutritional Assessment-Short Form(MNA-SF),handgrip strength,body mass,and body mass index(BMI).A two-way analysis of variance(ANOVA)was used to assess the interaction effects between TECAR and HMB.Results After the intervention,Group D(TECAR+HMB)demonstrated significant improvements across all metrics.The SPPB total score increased from 6.29±1.34 to 8.06±1.51(P<0.001),with notable enhancements in walking speed(2.71±0.86 vs.1.97±0.82),chair stand(2.60±0.55 vs.2.11±0.47),and balance(2.74±0.74 vs.2.20±0.76).MBI improved from 71.74±14.41 to 79.91±10.52(P<0.001).Handgrip strength increased from(13.65±5.05)kg to(15.72±4.89)kg(P=0.001).Body mass decreased from(81.78±9.02)kg to(76.95±9.89)kg(P<0.001),and BMI reduced from(30.14±1.68)kg/m2 to(28.34±2.33)kg/m2(P<0.001).Interaction analysis revealed significant synergistic effects between TECAR and HMB in improving the SPPB total scores(F=16.374,P<0.001,η2=0.107)and reducing BMI(F=14.328,P<0.001,η2=0.095).Conclusion TECAR therapy combined with HMB supplementation significantly enhances physical function,activities of daily living,and body composition in elderly patients with sarcopenic obesity,demonstrating a synergistic effect.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Immunotherapy has become a pivotal treatment regimen for hepatocellular carcinoma (HCC); however, its efficacy is influenced by various factors. Hepatitis B virus (HBV) infection is one of the primary etiological factors leading to HCC. HBV DNA replication can alter the immune microenvironment through multiple mechanisms, notably by upregulating the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1), thereby facilitating tumor immune escape. Paradoxically, this upregulation of PD-1/PD-L1 may enhance the response rate to PD-1/PD-L1 inhibitors and potentiate the antitumor effect. This review aims to summarize current research progress on the relationship between HBV DNA load and the efficacy of PD-1/PD-L1 inhibitors, explore the underlying mechanisms, and provide a scientific basis for promoting personalized treatment strategies for patients with HBV-related HCC.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective:To explore any myogenic effect of extracorporeal shock wave therapy (ESWT) on shoulder joint contracture.Methods:Sixty-eight patients with shoulder contracture were enrolled and randomly divided into a conventional therapy group ( n=34) and an ESWT group ( n=34) for this clinical trial. The conventional therapy group received standard rehabilitation treatment, while the ESWT group received additional extracorporeal shock wave therapy. In addition, 24 Sprague-Dawley rats were randomly assigned to a blank control group, a model group, a natural recovery group, or an ESWT animal group, each of 6. All of the groups except the blank control group had contracture modeled using plaster cast immobilization of the left shoulder joint. After successful modeling, the natural recovery group was routinely raised for two weeks, while the ESWT animal group received two weeks of extracorporeal shock wave intervention. In both the clinical and animal experiments, ESWT was administered twice weekly (every Tuesday and Friday) for two consecutive weeks. Before and after the treatment, the patient groups were assessed using a visual analog scale (VAS) for pain, shoulder range of motion (ROM), and the root mean square (RMS) values of the surface electromyographs of the peri-shoulder muscles. Shoulder ROM was assessed in all four of the rat groups after the ESWT treatment, and histological analysis of the supraspinatus muscle was performed. Results:After the treatment, both patient groups showed significant improvements in their average VAS scores, active and passive shoulder ROM, and RMS values. On average, the ESWT group demonstrated significantly greater improvements than the conventional therapy group in active forward flexion, passive forward flexion, active abduction, passive abduction, and the RMS values of the deltoid, biceps brachii, and triceps brachii muscles. After the treatment the left shoulder abduction angle had been reduced significantly in the model group (to 96.00±2.37)°, the natural recovery group (103.00±4.05)° and the ESWT animal group (121.33±4.89)° compared to the blank control group (154.50±2.35)°. Both the natural recovery group and the ESWT animal group had significantly greater shoulder abduction angles than the model group, and the ESWT animal group also demonstrated a significantly larger abduction angle than the natural recovery group. After the treatment, significant differences between the model group and the blank control group were observed in the cross-sectional area of left supraspinatus muscle fibers and the proportion of collagen. The ESWT animal group too exhibited significantly improved muscle fiber cross-sectional area and collagen proportion compared to the natural recovery group.Conclusions:Shoulder joint contracture is accompanied by significant myopathic changes (muscle atrophy and fibrosis). ESWT effectively ameliorates these problems while enhancing muscle strength and functional recovery.