ObjectiveTo investigate the effect and mechanism of cordycepin in inhibiting fat infiltration after rotator cuff injuries in rats by regulating the Wnt/β-catenin signaling pathway， providing a theoretical basis for clinical treatment of rotator cuff injuries. MethodsFifty SPF-grade female SD rats were used in this study， with 10 randomly selected as the blank group. A rotator cuff injury repair model was established by supraspinatus tendon and suprascapular nerve compression. The successfully modeled rats were randomized into model and low-dose （20 mg·kg^-1）， medium-dose （40 mg·kg^-1）， and high-dose （80 mg·kg^-1） cordycepin groups. After 6 weeks of treatment， the gait analysis was performed to assess the limb function in rats. Oil red O staining and Masson staining were employed to observe pathological changes in the muscle tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the serum. Immunohistochemistry （IHC） was employed to detect the expression of peroxisome proliferator-activated receptor γ （PPARγ） and CCAAT/enhancer-binding protein α （C/EBPα）， which are markers of adipogenesis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of Wnt3a， Wnt10b， and β-catenin. ResultsCompared with the blank group， the model group showed decreases in stride length and paw print area （P<0.01）， an increase in ratio of wet muscle mass reduction and a decrease in muscle fiber cross-sectional area （P<0.05）， and decreased ratios of fat infiltration area and collagen fiber area （P<0.01）. Additionally， the model group showed elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， up-regulated protein levels of PPARγ and C/EBPα （P<0.01）， and down-regulated mRNA and protein levels of Wnt3a， Wnt10b， and β-catenin （P<0.05， P<0.01）. Compared with the model group， the low-， medium-， and high-dose cordycepin groups showed increases in stride length and paw print area （P<0.01）， a decrease in ratio of wet muscle mass reduction and an increase in muscle fiber cross-sectional area （P<0.05）， and increases in ratios of fat infiltration area and collagen fiber area （P<0.05， P<0.01）. In addition， cordycepin lowered the serum levels of IL-1β， IL-6， and TNF-α （P<0.05， P<0.01）， down-regulated the protein levels of PPARγ and C/EBPα （P<0.01）， and up-regulated the mRNA and protein levels of Wnt3a， Wnt10b， and β-catenin （P<0.05， P<0.01）. ConclusionCordycepin can improve the limb function， alleviate rotator cuff muscle atrophy， fat infiltration， and fibrosis， and inhibit inflammation in rats by regulating the Wnt/β-catenin signaling pathway.

OBJECTIVE To investigate the multi-target mechanism of action of Poecilobdella manillensis lyophilized powder(SZ) against hyperuricemia(HUA) based on network pharmacology and transcriptomics approaches, combined with animal experiments. METHODS Utilizing Symmap, SwissTargetPrediction, and Pharmmapper databases, the potential active components and corresponding targets of SZ were obtained. Through the Gene Cards and OMIM databases, HUA-related targets were obtained. By taking the intersection mapping, the common targets of SZ and HUA were identified. Cytoscape 3.9.0 software was used to construct a drug component-disease target interaction network, and in combination with the STRING database, a protein interaction network was built and core targets were screened. The DAVID database was used to perform GO biological function annotation and KEGG pathway enrichment analysis on the intersecting targets. A mouse model of HUA was constructed using potassium oxyzate combined with high purine diet, and the effects of SZ on these mice were examined using ELISA and biochemical index detection. qRT-PCR was used to validate the results of RNA-Seq and network pharmacology enrichment analysis. RESULTS Network pharmacological analysis identified 11 major bioactive substances in SZ and 72 potential targets involved in the treatment of hyperuricemia, involving multiple biological processes and different signaling pathways. It was shown that SZ significantly reduced serum uric acid, creatinine and urea nitrogen levels in hyperuricemic mice by inhibiting xanthineoxidase activity. SZ also reduced the levels of URAT1 while increasing the levels of ABCG2. RNA sequencing analysis revealed that there were 112, 536 and 107 differentially expressed genes in the model group vs treated group, control group vs model group and control group vs treated group, respectively. qRT-PCR results indicated that SZ downregulated the expression of genes related to Th17 cell differentiation as well as mRNA of genes on IL-17 and PI3K/Akt signaling pathways. CONCLUSION SZ has therapeutic effects on hyperuricemia. The mechanism of action maybe related to the inhibition of hepatic xanthineoxidase activity, down-regulation of URAT1 levels, up-regulation of ABCG2 levels, affecting the differentiation of Th17 cells and thus the IL-17 signaling pathway, thereby reducing the inflammatory response.

Objective To observe the application effect of montelukast sodium combined with terbutaline on cough variant asthma(CVA)in children and its influence on airway remodeling and peripheral blood inflammatory indicators.Methods The children with CVA were randomly classified into control group and treatment group.The control group was given aerosol inhalation of terbutaline(5 mg each time,twice a day),and on the basis of the control group,the treatment group was combined with oral administration of montelukast sodium granules(4 mg each time,once a day,taking before going to bed),and both groups were continuously treated for 3 months.The clinical efficacy,airway cross-section area(AO),airway lumen area(AI),airway wall thickness(T),airway wall area(WA),serum interleukin-5(IL-5),eosinophilic chemotactic factor(Eotaxin),macrophage inflammatory protein-1α(MIP-1α)and T lymphocyte subgroups CD4+,CD8+and CD4+/CD8+were compared between the two groups of children,and the medication safety was assessed.Results Fifty-three cases in control group and 53 cases in treatment group were included.After treatment,the total effective rates in treatment group and control group were 96.23％(51 cases/53 cases)and 83.02％(44 cases/53 cases),respectively(P＜0.05).The AO values in treatment group and control group were(39.42±3.67)and(45.69±4.92)mm2;AI values were(22.36±2.85)and(27.06±3.18)mm2;T values were(1.12±0.28)and(1.44±0.33)mm;WA values were(53.82±4.17)and(60.13±4.66)mm2;serum IL-5 levels were(25.46±5.83)and(41.46±7.64)ng·L-1;Eotaxin levels were(181.24±30.05)and(238.21±39.42)ng·L-1;MIP-1a levels were(15.24±3.67)and(22.43±4.05)ng·L-1;CD4+levels were(37.18±4.06)％and(33.57±3.82)％;CD8+levels were(24.08±3.15)％and(27.31±3.07)％;and CD4+/CD8+levels were 1.54±0.33 and 1.24±0.28,respectively(all P＜0.05).The total incidences of adverse drug reactions in treatment group and control group were 9.43％(5 cases/53 cases)and 3.77％(2 cases/53 cases),respectively(P＞0.05).Conclusion Montelukast sodium combined with terbutaline has an exact efficacy in the treatment of CVA in children,and it can effectively reverse airway remodeling,reduce inflammation level and enhance immune function,and it has good safety.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

OBJECTIVE To investigate the protective effect proanthocyanidin B2(PC-B2) on oxidative damage and apoptosis of mouse astrocytes(AS) induced by hydrogen peroxide(H2O2) and its mechanism. METHODS AS were isolated and cultured from neonatal C57BL/6 mice(1−3 d). The optimal concentration of H2O2 and PC-B2 was divided into four groups: normal group, normal+PC-B2 group(100 μg·mL‒1 PC-B2 treated for 24 h), H2O2 model group(200 μmol·L‒1 H2O2 treated for 24 h), PC-B2 group(200 μmol·L‒1 H2O2 and 100 μg·mL‒1 PC-B2 treated for 24 h). The cell viability of each group was detected by CCK-8 method. Cytotoxicity was detected by LDH method. The antioxidant capacity was detected by ABTS and DPPH. The content of MDA and the activity of SOD, CAT and GSH-Px were detected by ELISA kit. Detection of apoptosis in each group was done by TUNEL staining. The mRNA and protein expression levels of Bax, Bcl-2, Caspase-3, Akt/Stat3, p-Akt, p-Stat3 and Nrf2/HO-1 in AS were detected by RT-PCR and Western blotting, respectively. RESULTS PC-B2 could significantly enhance cell viability and inhibit AS apoptosis. Compared with the H2O2 model group, PC-B2 intervention could significantly reduce the content of LDH and MDA in AS, and increase the activity of SOD, CAT and GSH-Px. PC-B2 intervention could inhibit the mRNA and protein expression of Bax and Caspase-3, and up-regulate the mRNA and protein expression of Akt/Stat3, Bcl-2, Nrf2/HO-1. CONCLUSION PC-B2 can enhance the antioxidant capacity of AS through Akt/Stat3 and Nrf2/HO-1 pathways, therefore reduce H2O2-induced AS oxidative damage and apoptosis.

Objective:To investigate the predictive efficacy of brain natriuretic peptide(BNP),angiotensin Ⅱ(An-gⅡ),erythrocyte distribution width(RDW)and neutrophil/lymphocyte ratio(NLR)for postoperative left ventric-ular systolic dysfunction(LVSD)in patients with acute anterior myocardial infarction(AAMI).Methods:A total of 160 AAMI patients treated in our hospital from January 2018 to January 2022 were selected.According to left ventricular ejection fraction(LVEF)after percutaneous coronary intervention,they were divided into no LVSD group(LVEF＞40％,n=110)and LVSD group(LVEF≤40％,n=50).Baseline data were compared between two groups.Multivariate Logistic regression analysis was used to analyze influencing factors of postoperative LVSD in AAMI patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of single and combined detection of BNP,AngⅡ,RDW and NLR for postoperative LVSD in AAMI patients.Results:Compared with no LVSD group,there were significant rise in levels of BNP[(347.52±82.66)pg/ml vs.(405.55±105.47)pg/ml],AngⅡ[(238.11±20.43)ng/ml vs.(254.58±22.53)ng/ml],RDW[(22.88±5.25)％vs.(25.52±5.58)％]and NLR[(4.34±1.09)vs.(5.31±1.50)]in LVSD group(P＜0.01 all);BNP,AngⅡ,RDW and NLR were independent risk factors for postoperative LVSD in AAMI patients(OR=2.002～3.692,P＜0.05 or＜0.01);predictive value of combined detection of BNP,AngⅡ,RDW and NLR for postoperative LVSD in AAMI patients was significantly higher than those of single detection[area under the curve(AUC):0.809 vs.0.650,0.696,0.641,0.694,P＜0.01 all].Conclusion:Left ventricular systolic function is closely associated with levels of BNP,AngⅡ,RDW and NLR in AAMI patients.Combined detection of the above indexes can effectively predict postoperative left ventricular systolic dysfunction in these patients.

Objective To investigate the effect of Ilizarov technique combined with rotational center dome-shaped osteoto-my in the treatment of juvenile distal femoral valgus deformity.Methods A retrospective study was conducted to analyze the clinical data of 11 patients with valgus deformity of the distal femur who had been admitted and followed up completely from January 2016 to October 2020.There were 7 males and 4 females.The 6 patients were on the right side and 5 patients were on the left side.The age ranged from 10 to 14 years old.The center of roration of angulation(CORA)was identified at the distal femur deformity,and dome-shaped osteotomy was performed with the CORA as the midpoint.The annular external fixator was installed according to the needle threading principle of Ilizarov external fixation,and the distal femur was cut off.The valgus deformity under visual inspection of the distal femur was corrected immediately,and the external fixator was fixed and main-tained.The residual deformity and shortening were corrected according to the force line and length of the lower limbs suggested by the weight-bearing full-length anteroposterior and lateral X-rays of both lower limbs.Results All 11 patients were followed up for 13 to 25 months.The time of wearing external fixator was 12 to 17 weeks.In the last follow-up,both lower limbs were measured by the weight-bearing full-length anteroposterior and lateral X-rays,and the length of both lower limbs of 11 patients were equal,and the deformities were corrected.The score of hospital for special surgery(HSS)was used to evaluate the knee function,all of which were excellent.Conclusion The Ilizarov technique was applied in the treatment of distal femoral valgus deformity in adolescents using a rotating central dome-shaped osteotomy.Visual femoral valgus deformity was corrected imme-diately during the operation.After the operation,residual deformities and shortening were dynamically adjusted and corrected according to the force line and shortening degree of lower extremities indicated by the weight-bearing anteroposterior and lateral radiographs of both lower limbs,with minimal damage and fast recovery.