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.

Background While A few studies have suggested associations between ambient temperature and cardiac autonomic function, the relationship between hourly temperature variations and heart rate variability (HRV) remains unclear. Objective To examine the acute effects and lag patterns of short-term ambient temperature exposure on HRV at an hourly temporal resolution during cold and warm seasons, and to further characterize the exposure-response relationships. Methods We conducted a longitudinal panel study involving 1047 eligible participants who ordered repeated 24 h ambulatory electrocardiogram monitoring at the First Affiliated Hospital of Xinjiang Medical University in Urumqi, Xinjiang Uygur Autonomous Region, China, between March 2020 and March 2022. Twelve HRV parameters were extracted, including standard deviation of all NN intervals (SDNN), standard deviation of the 5 min averages of NN intervals (SDANN), standard deviation of NN intervals index (SDNNIDX), root mean square of successive differences of adjacent NN intervals (rMSSD), triangle index (TI), percent of NN50 in the total number of NN intervals (pNN50), total power (TP), ultralow frequency (ULF), very low frequency (VLF), low frequency (LF), high frequency (HF), and ratio of low frequency to high frequency (LF/HF). Hourly meteorological data (mean temperature and relative humidity) were obtained from the nearest monitoring stations to participants' residences. Linear mixed effects models (LME) and generalized additive mixed effects models (GAMM) were employed to assess temperature-HRV associations and lag patterns during cold (from October to March next year) and warm (from April to September) seasons, with stratification by sex and age. Results A total of 1047 Urumqi residents who had repeated 24 h ambulatory electrocardiograms were included in this study. In both cold and warm seasons, the exposure-response relationship between ambient temperature and HRV showed an approximately linear negative correlation with no threshold effect; HRV parameters decreased as ambient temperature increased. The correlation between ambient temperature and HRV usually began at a lag of 6 h and disappeared around 24 h lag. The cold season induced a stronger effect on HRV decline, and for every 1 °C increase in ambient temperature during the cold season from lag 0 to 6 h, SDNN decreased by 0.72%, SDNNIDX decreased by 1.46%, TI decreased by 0.07%, SDANN decreased by 1.23%, rMSSD decreased by 1.00%, pNN50 decreased by 2.74%, TP decreased by 3.30%, ULF decreased by 3.74%, VLF decreased by 3.76%, LF decreased by 2.75%, HF decreased by 2.49%, and LF/HF decreased by 0.74%; for every 1 °C increase in ambient temperature during the warm season, SDNN decreased by 0.56%, SDNNIDX decreased by 1.08%, TI decreased by 0.29%, SDANN decreased by 0.56%, rMSSD decreased by 0.68%, pNN50 decreased by 2.11%, TP decreased by 2.64%, ULF decreased by 3.14%, VLF decreased by 2.74%, LF decreased by 1.85%, HF decreased by 1.68%, and LF/HF decreased by 0.47%. Conclusion Elevated ambient temperatures in Urumqi are significantly associated with decreased HRV in the residents, affecting cardiac autonomic function.

Objective:To explore the risk factors associated with aneurysmal subarachnoid haemorrhage(aSAH)complicated with acute hydrocephalus(aHCP),and to provide the clinical reference for the early identification and intervention of these patients.Methods:The clinical data and laboratory indexes of 175 patients with aSAH were retrospectively analysed,and the patients were divided into aHCP group(n=56)and non-aHCP group(n=119)according to whether they presented with aHCP after the onset of the disease.Univariate analysis and binary logistic regression were applied to identify the risk factors for the aHCP in aSAH patients,and receiver operating characteristic(ROC)curve analysis with area under the curve(AUC)was used to evaluate the predictive value of these factors.Results:A total of 56(32.0%)out of 175 aSAH patients included developed aHCP after the onset of the disease.Compared with non-aHCP group,the levels of neutrophil count,blood glucose,neutrophil-albumin ratio(NAR),platelet-lymphocyte ratio(PLR),neutrophil-lymphocyte ratio(NLR),monocyte-lymphocyte ratio(MLR),systemic immune-inflammatory index(SII),systemic inflammatory response index(SIRI),and systemic inflammation composite index(AISI)of the patients in aHCP group were significantly increased(P<0.05),the level of lymphocyte count was significantly decreased(P<0.05),the Hunt-Hess grade and modified Fisher grade were higher(P<0.05),and the incidence of ventricular haematochezia was more high(P<0.05).The binary Logistic regression analysis results showed that the elevated levels of NAR(OR=2.237,95%CI:1.063-4.708,P=0.034)and NLR(OR=1.210,95%CI:1.095-1.337,P<0.01)were the independent risk factors for the development of aHCP after aSAH.The ROC curve analysis showed that the AUC of NAR was 0.812(95%CI:0.745-0.878,P<0.001),the AUC of NLR was 0.844(95%CI:0.785-0.903,P<0.001),and the combined AUC of NAR and NLR was 0.854(95%CI:0.798-0.910,P<0.001).Conclusion:NAR and NLR are independent risk factors for the development of aHCP in aSAH patients.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Obstructive sleep apnea-hypopnea syndrome(OSAHS)is a chronic disease that characteristics is multi system damage,which core pathological mechanism involves a complex interaction between structural abnormalities of the upper airway and imbalances in neuromuscular regulation.With continuous advancements in imaging technique,upper airway imaging technique has been a key tool that reveals pathological characteristics of OSAHS heterogeneity,and guides individual diagnosis and treatment.This article explored OSAHS's pathogenesis,and systematically sorted out the application of various imaging techniques,including X-ray cephalometry,computed tomography(CT),magnetic resonance imaging(MRI),ultrasound,and drug-induced sleep endoscopy(DISE)in the diagnosis and treatment for OSAHS,which focuses on an analysis for their values in the location of them at obstructive plane,treatment decision and the prediction for curative effect.In addition,this article conducted a prospect for multimodal imaging fusion,artificial intelligence-assisted analysis and other development in these imaging techniques in future.By comparing the clinical applicability and limitations of each kind of technique,this review provided imaging basis for optimizing the pathway of OSAHS's clinical diagnosis and treatment,promoting the shift from conventional classification to precision intervention,so as to ultimately improve the quality of managing disease.

OBJECTIVE: To review the clinical characteristics of patients with traumatic spinopelvic dissociation (SPD) and explore the diagnostic and therapeutic methods. METHODS: A clinical data of 22 patients with SPD who underwent surgical treatment between March 2019 and August 2024 was retrospectively analyzed. There were 13 males and 9 females, with an average age of 35.5 years (range, 14-61 years). The causes of injury included falling from height in 16 cases, traffic accidents in 5 cases, and compression injury in 1 case. Sacral fractures were classified based on morphology into "U" type (9 cases), "H" type (7 cases), "T" type (4 cases), and "λ" type (2 cases). According to the Roy-Camille classification, there were 4 cases of type Ⅰ, 12 cases of type Ⅱ, 2 cases of type Ⅲ, and 4 cases of type Ⅳ. The Cobb angle was (35.7± 22.0)°. Sixteen patients were accompanied by lumbosacral trunk and cauda equina nerve injury, which was classified as grade Ⅱ in 5 cases, grade Ⅲ in 5 cases, and grade Ⅳ in 6 cases according to the Gibbons grading. The time from injury to operation was 2-17 days (mean, 5.7 days). Based on the type of sacral fracture and sacral nerve injury, 6 cases were treated with closed reduction and minimally invasive percutaneous sacroiliac screw fixation, 16 cases were treated with open reduction and lumbar iliac fixation (8 cases)/triangular fixation (8 cases). Among them, 11 patients with severe fracture displacement and kyphotic deformity leading to sacral canal stenosis or bony impingement within the sacral foramen underwent laminectomy and sacral nerve decompression. X-ray films and CT were reviewed during followed-up. The Matta score was used to evaluate the quality of fracture reduction. At last follow-up, the Majeed score was used to assess the functional recovery, and the Gibbons grading was used to evaluate the nerve function. RESULTS: All operations were successfully completed. All patients were followed up 8-64 months (mean, 20.4 months). Two patients developed deep vein thrombosis of the lower limbs, 2 had incision infections, and 1 developed a sacral pressure ulcer; no other complications occurred. Radiological examination showed that the Cobb angle was (12.0±6.8)°, which was significantly different from the preoperative one ( t=6.000, P<0.001). The Cobb angle in 16 patients who underwent open reduction was (14.9±5.5)°, which was significantly different from the preoperative one [(46.8±13.9)° ] ( t=8.684, P<0.001). According to the Matta scoring criteria, the quality of fracture reduction was rated as excellent in 8 cases, good in 7 cases, fair in 5 cases, and poor in 2 cases, with an excellent and good rate of 68.2%. Bone callus formation was observed at the fracture site in all patients at 12 weeks after operation, and bony union achieved in all cases at last follow-up, with a healing time ranging from 12 to 36 weeks (mean, 17.6 weeks). At last follow-up, the Majeed score was rated as excellent in 7 cases, good in 10 cases, fair in 4 cases, and poor in 1 case, with an excellent and good rate of 77.3%. One patient experienced a unilateral iliac screw breakage at 12 months after operation, but the fracture had already healed, and there was no loss of reduction. Among the 16 patients with preoperative sacral nerve injury, 11 cases showed improvement in nerve function (6 cases) or recovery (5 cases). CONCLUSION SPD with low incidence, multiple associated injuries, and high incidence of sacral nerve injury, requires timely decompression of the sacral canal for symptomatic sacral nerve compression, fractures reduction, deformities correction, and stable fixation.
Humans ; Adult ; Female ; Male ; Retrospective Studies ; Middle Aged ; Spinal Fractures/diagnostic imaging* ; Adolescent ; Sacrum/diagnostic imaging* ; Fracture Fixation, Internal/methods* ; Young Adult ; Pelvic Bones/surgery* ; Treatment Outcome ; Bone Screws

Obstructive sleep apnea-hypopnea syndrome(OSAHS)is a chronic disease that characteristics is multi system damage,which core pathological mechanism involves a complex interaction between structural abnormalities of the upper airway and imbalances in neuromuscular regulation.With continuous advancements in imaging technique,upper airway imaging technique has been a key tool that reveals pathological characteristics of OSAHS heterogeneity,and guides individual diagnosis and treatment.This article explored OSAHS's pathogenesis,and systematically sorted out the application of various imaging techniques,including X-ray cephalometry,computed tomography(CT),magnetic resonance imaging(MRI),ultrasound,and drug-induced sleep endoscopy(DISE)in the diagnosis and treatment for OSAHS,which focuses on an analysis for their values in the location of them at obstructive plane,treatment decision and the prediction for curative effect.In addition,this article conducted a prospect for multimodal imaging fusion,artificial intelligence-assisted analysis and other development in these imaging techniques in future.By comparing the clinical applicability and limitations of each kind of technique,this review provided imaging basis for optimizing the pathway of OSAHS's clinical diagnosis and treatment,promoting the shift from conventional classification to precision intervention,so as to ultimately improve the quality of managing disease.

To elucidate the genomic characteristics of Salmonella strains derived from sheep,this study employed various methods,including bacterial isolation and identification,biochemical identi-fication,pathogenicity test,whole-genome sequencing,and BLAST comparison,along with the screening of integrative conjugative elements(ICE)using ICEfinder and EasyFig for comparative analysis,as well as plasmid comparisons utilizing PlasmidBrig.The results revealed the isolation of a Gram-negative,non-spore-forming bacillus from nasal swabs of diseased sheep,which formed gray-white,smooth-surfaced,and neatly edged circular colonies on TSA sheep blood agar.On XLT-4 agar medium,it produced smooth-surfaced,white,circular colonies.The bacterium was identified as Salmonella enterica through 16S rRNA sequencing and biochemical identification.This bacteri-um induces hemorrhaging in the intestines of guinea pigs,resulting in their demise within a 48-hour period.The pathogen exhibits high virulence.Whole-genome alignment demonstrated a high degree of homology with Salmonella enterica subsp.diarizonae serotype 61:k:1,5,(7).ICE screen-ing and comparative analysis indicated the presence of a novel ICE in this strain,characterized by a core structural framework that includes an integrative shear module,a mobilizable processing mod-ule,a conjugative pair formation module,and a regulatory module.Notably,ICE from different spe-cies containing the same integrase exhibited identical inverted repeat sequences and insertion sites at tRNAPhe.Plasmid homology comparisons revealed that plasmid sequences from different strains of Salmonella enterica subsp.diarizonae serotype 61:k:1,5,(7)also showed high homology;however,the homology with plasmid sequences from other Salmonella and Escherichia coli strains was only 50％.These findings indicate that the isolated strain is Salmonella enterica subsp.diarizonae serotype 61:k:1,5,(7)and contains a novel ICE as well as a plasmid.This study fur-ther enriches the molecular epidemiology of Salmonella and provides a theoretical basis for the prevention and control of infections caused by this pathogen.