ObjectiveTo observe the clinical efficacy of Gandou Fumu Granules （GDFMG） combined with sodium dimercaptosulphonate （DMPS） on liver fibrosis in Wilson disease （WD） patients with the syndrome of phlegm and blood stasis， evaluate its effect on cuproptosis-related indicators， and explore the possible mechanisms of cuproptosis in WD-related liver fibrosis. MethodsSixty WD patients diagnosed with the syndrome of phlegm and blood stasis between January 2023 and December 2023 were randomly divided into a control group and an observation group， with 30 patients in each group. The control group received the copper chelator DMPS for the first 6 days， followed by calcium gluconate injection for the next 2 days， completing an 8-day treatment cycle. The observation group received GDFMG in addition to the treatment regimen of the control group， with both groups treated for 21 cycles. A Beckman fully automated biochemical analyzer was used to detect levels of type Ⅳ collagen （CⅣ）， hyaluronic acid （HA）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢ-NP）， and serum copper （SCu） before and after treatment in both groups. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， and dihydrolipoamide S-acetyltransferase （DLAT）. Atomic absorption spectroscopy measured 24-hour urine copper levels before treatment and after the 7， 14， and 21 treatment cycles in both groups. An Fibro Touch （FT） non-invasive liver fibrosis diagnostic device was used to measure liver stiffness （LSM） in both groups before and after treatment. Traditional Chinese medicine syndrome score （TCMSS） was evaluated at the same intervals. Clinical efficacy， adverse events， and safety indicators were also compared. ResultsAfter treatment， levels of CⅣ， HA， LN， and PⅢNP significantly decreased in both groups compared to pre-treatment levels （P<0.01）. The observation group showed a more pronounced reduction compared to the control group （P<0.05）. There were no statistically significant differences in SCu levels in both groups before and after treatment. After treatment， levels of FDX1，LIAS and DLAT significantly increased in both groups（P<0.01）. The observation group showed more notable improvements in these indicators than the control group （P<0.05）. After the 7， 14， 21 treatment cycles， 24-hour urine copper levels significantly increased in both groups compared to pre-treatment levels （P<0.01）. The observation group had a greater increase in 24-hour urine copper levels than the control group after treatment （P<0.05，P<0.01）， and although 24-hour urine copper levels increased after 7 cycles， a gradual decline was observed in subsequent cycles. After treatment， LSM levels significantly decreased in both groups compared to pre-treatment levels （P<0.01）， with the observation group showing a greater reduction than the control group （P<0.05）. Clinical efficacy was significantly better in the observation group than the control group （P<0.05）. No significant differences in the incidence of adverse events or safety indicators were observed between the two groups after treatment. ConclusionGDFMG combined with DMPS can reduce LSM in WD patients with liver fibrosis and the syndrome of phlegm and blood stasis， inhibit cuproptosis， and improve clinical efficacy.

ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.

Objective To investigate the population density and seasonal fluctuations of Aedes albopictus in Guangzhou City, Guangdong Province, from 2021 to 2023, so as to provide insights into A. albopictus control and management of dengue fever. Methods The surveillance of A. albopictus density was performed in all surveillance sites assigned across all streets (townships) in Guangzhou City during the period from January to December from 2021 to 2023. The surveillance frequency was twice every half month from May to September, and once every month for the rest of a year. In each surveillance period, A. albopictus mosquito larvae were captured from indoor and outdoor small water containers in residential areas, parks, medical facilities, schools, other government sectors and social organizations, construction sites, special industries and others for mosquito species identification. Adult mosquitoes were captured using electric mosquito suction apparatus for species identification and gender classification. Adult mosquitoes and mosquito eggs were collected with mosquito and egg traps at the breeding and dwelling places of Aedes mosquitoes for identification. The mosquito oviposition index (MOI), Breteau index (BI), adult mosquito density index (ADI) and standard space index (SSI) were calculated. The A. albopictus density was classified into grades 0, 1, 2 and 3 in each surveillance site, with Grade 0 density defined eligible, and the eligible rate of A. albopictus density was calculated at all surveillance sites each year from 2021 to 2023. In addition, the changing trends in MOI, SSI, BI and ADI of A. albopictus were analyzed in Guangzhou City from 2021 to 2023. Results The eligible rates of A. albopictus density were 61.69%, 68.75% and 55.15% in surveillance sites of Guangzhou City from 2021 to 2023 (χ² = 297.712, P < 0.001), and appeared a tendency towards a reduction followed by a rise each year, which gradually reduced since January, maintained at a low level during the period between May and October, and gradually increased from November to December. The MOI, SSI, BI and ADI of A. albopictus all appeared a tendency towards a rise followed by a reduction in Guangzhou City during the period between January and December from 2021 to 2023. The BI of A. albopictus peaked in the first half of June in 2021 (4.03), the first half of July in 2022 (3.89) and the last half of August in 2023 (5.02), and the SSI of A. albopictus peaked in the last half of June in 2021 (0.93), the last half of May in 2022 (0.59), and the last half of June (0.94) and the first half of September in 2023 (1.12). In addition, the MOI of A. albopictus peaked in the first half of May in 2021 (8.64), the first half of June in 2022 (8.96), and the last half of May (10.21) and the last half of June in 2023 (10.89), and the ADI of A. albopictus peaked in the first half of June in 2021 (3.41), the last half of June in 2022 (4.06), and the first half of July in 2023 (3.61). Conclusions The density of A. albopictus is high in Guangzhou City during the period from May to October, and the risk of local outbreak caused by imported dengue fever is high. Persistent intensified surveillance of the density and seasonal fluctuation of A. albopictus is recommended and timely mosquito prevention and control is required according to the fluctuation in the A. albopictus density.

In recent years， NOD-like receptor protein 3 （NLRP3） inflammasome in tumors has become a research hotspot， especially in melanoma， colorectal cancer， lung cancer， and breast cancer， and more and more evidence has shown that inflammation plays a role in the development， progression， angiogenesis， and invasion of cancer. Hepatocellular carcinoma （HCC） is the most common type of primary liver cancer， and there are still controversies over the role of NLRP3 inflammasome in the development and progression of HCC. Therefore， this article reviews the potential impact of NLRP3 inflammasome in the progression of HCC and its mechanism of action in anticancer therapy， and it is believed that NLRP3 inflammasome can be used as an effective therapeutic target for HCC patients.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To investigate the effect of trunk control on the biomechanical characteristics of lower limb movements during Asian squats(AS)and Western squats(WS)in young adults to provide empirical support for the application and promotion of deep squat training.Methods Twenty-four healthy young male collegiate students performed AS and WS with and without bar control,and their lower limb kinematic and kinetic characteristics were collected using an infrared light-point motion capture system and a three-dimensional(3D)dynamometer.The 3D angles of the lower limbs were obtained using Cortex-642.6.2 software,based on the calculation of Euler angles,and the 3D moments were obtained by applying the inverse dynamics method.The effects of trunk control and deep squatting posture on the lower limb kinematic characteristics were examined using a two-factor analysis of variance with a 2×2 repeated design.Results There was no significant interaction between trunk control and the deep squatting posture for either kinematic or kinetic parameters(P>0.05).The WS group had a large knee flexion angle,peak patellofemoral contact force,and ratio of peak hip and knee extension moments,and small ankle dorsiflexion and hip flexion angles(P<0.05).The deep squat with a bar had a large ankle dorsiflexion angle,peak patellofemoral contact force,and hip flexion angle as well as a small knee flexion angle and ratio of peak hip and knee extension moments(P<0.05).Conclusions WS is helpful for training hip extension muscle groups,whereas AS is helpful for training knee extension muscle strength.The peak patellofemoral joint contact force of the WS is significantly greater than that of the AS;therefore,it is recommended that patients with patellofemoral joint pain use the AS.A squat with a bar can compensate for the body's balance;thus,people with limited ankle dorsiflexion range of motion or anterior tibial muscle weakness may consider trunk control training,such as a deep squat with a bar.This may help improve lower limb stability during squats.

Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.

Objective:To evaluate the effect of the impaction of posterior wall on the prognosis following open reduction and internal fixation for fractures of acetabular posterior wall.Methods:A retrospective study was conducted to analyze the data from the 83 patients with fracture of acetabular posterior wall who had been consecutively treated by open reduction and internal fixation at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital from January 2017 to December 2020. The patients were divided into 2 groups based on involvement of posterior wall impaction. In the impaction group of 33 cases, there were 26 males and 7 females with an age of (47.4±11.6) years; in the non-impaction group of 50 cases, there were 43 males and 7 females with an age of (41.3±12.0) years. The quality of postoperative fracture reduction, the function of the affected hip at the last follow-up, and the complication rate during follow-up were compared between the 2 groups. Multifactorial binary logistic regression and age subgroups were used to analyze the effects of posterior wall impaction on functional outcomes.Results:The age, rate of associated injuries in other body parts, and rate of posterior wall comminution in the impaction group were significantly higher than those in the non-impaction group ( P<0.05), but there was no statistically significant difference in other general data of patients between the 2 groups ( P>0.05). All patients were followed up for (44.5±13.3) months after surgery. The rate of anatomical reduction in the non-impaction group (96.0%, 48/50) was significantly higher than that in the impaction group (57.6%, 19/33) ( P<0.05), and the good and excellent rate by the modified Merle d'Aubigné & Postel scale at the last follow-up in the non-impaction group (84.0%, 42/50) was significantly higher than that in the impaction group (51.5%, 17/33) ( P<0.05). There was no significant difference in the incidence of complications between the 2 groups ( P>0.05). After adjusting for age and gender, the difference in hip function was still significantly different between the 2 groups ( OR=0.23, 95% CI: 0.06 to 0.79, P=0.020). The effect of posterior wall impaction on functional outcomes was statistically significant in patients aged ≥50 years ( P=0.008), whereas the difference was not statistically significant in patients aged <50 years ( P=0.194). Conclusions:Compared with non-impaction ones, acetabular fractures of posterior wall impaction tend to lead to poorer quality of reduction, which in turn affects the postoperative recovery of hip joint function. The impact of impaction fractures on functional recovery is more significant in patients aged 50 years and above.

Objective To investigate the efficacy of transjugular intrahepatic portosystemic shunt(TIPS)in preventing rebleeding in patients with hepatocellular carcinoma(HCC)comorbid with esophagogastric variceal bleeding and the influencing factors for prognosis.Methods A retrospective analysis was performed for the clinical data of 35 HCC patients comorbid with esophagogastric variceal bleeding who were admitted to Zengcheng Branch of Nanfang Hospital,Southern Medical University,and were treated with TIPS from July 2019 to April 2023.The Kaplan-Meier curve was used to assess rebleeding rate and survival rate after TIPS,and the Cox regression model was used to investigate the influencing factors for postoperative rebleeding and survival.Results The TIPS procedure was technically successful in all patients,with a median follow-up time of 16.4 months.During follow-up,11 patients(31.4%)experienced esophagogastric variceal rebleeding,with the 1-month,3-month,and 1-year rebleeding rates of 5.7%,17.1%,and 28.6%,respectively.White blood cell count(WBC)(risk ratio[HR]=1.31,95%confidence interval[CI]:1.04-1.64,P=0.021),number of tumors≥3(HR=35.68,95%CI:1.74-733.79,P=0.021),and portal pressure gradient before TIPS(HR=0.85,95%CI:0.73-0.99,P=0.032)were independent predictive factors for rebleeding after TIPS.Shunt dysfunction was observed in 5 patients after surgery.A total of 19 patients died during follow-up,with a median survival time of 9.6 months.Portal vein tumor thrombosis(PVTT)(HR=7.04,95%CI:1.31-37.78,P=0.023),total bilirubin(TBil)(HR=1.02,95%CI:1.00-1.03,P=0.042),and serum albumin(HR=0.82,95%CI:0.72-0.94,P=0.004)were independent predictive factors for survival after TIPS.Conclusion TIPS procedure can be used as a therapeutic option to prevent esophagogastric variceal rebleeding in patients with HCC.Patients with a relatively high level of WBC or TBil or those with PVTT tend to have a poorer prognosis,and the application of TIPS treatment in such patients should be determined with caution.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)