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.

With the continuous development of medical science and the widespread use of antibiotics,the problem of bacterial resistance is increasing,especially the increasing carbapenem-resistant Enterobacteriaceae(CRE)infection,and the high mortality rate,which brings great challenges to clinical treatment.In this paper,the mechanism of drug resistance,existing antibac-terial drugs,and exploratory treatment options for CRE are reviewed,and the research progress in treating CRE infection is dis-cussed to provide more reliable evidence and a theoretical basis for clinical practice.

Objective To analyze the registered clinical trials of headache treated by TCM;To discuss the current research status;To provide reference for the optimization of subsequent clinical trial research plans.Methods All clinical trials of headache treated by TCM were retrieved from the ChiCTR and the ClinicalTrials.The retrieval time was from the database establishment to May 22,2023.The general characteristics,study types,intervention measures and outcome indicators of the trials were analyzed respectively.Results A total of 104 registered studies were included,with the number of registered studies increasing since 2004 and reaching a peak in 2020,involving 25 provincial administrative regions or countries and 69 clinical trial institutions;the funding sources were mainly scientific research funds of universities,national finance and local finance.The research type was mainly intervention research;the designing scheme was mainly randomized parallel control study;the high frequency random method was simple random method;45 registered studies used blind methods.Exploratory studies/pre-trials were the most commonly used in the phases of clinical researches.Most of the registered studies were single-center clinical trials with a total sample size of 9 648 patients.The main interventions were acupuncture and oral Chinese medicines.The high frequency outcome indicators included life quality of score,headache attack frequency,headache attack days and headache severity,etc.There were some problems in outcome indicators,such as non-standard,lack of TCM characteristic advantages,and insufficient patient participation.Conclusion The number of registered studies of headache treated by TCM has increased by year,but there are some problems in design elements,such as random method,blind method,number of research centers,sample size and the setting of outcome indicator.

Objective To observe the value of B1 corrected T1 mapping for distinguishing pathological types and differentiation degrees of lung cancers.Methods A total of 74 lesions in 65 patients with lung cancers were prospectively enrolled,including 49 poorly differentiated lesions and 25 moderately or well differentiated ones,i.e.42 adenocarcinomas,14 squamous cell carcinomas and 18 small cell lung cancers(all poorly differentiated).B1 corrected T1 mapping was performed,ROI(ROI1 and ROI2)were delineated using 2 methods,and T1 values of different pathological types and differentiation degrees lung cancers were compared.The receiver operating characteristic(ROC)curves were drawn,and the areas under the curve(AUC)were calculated.Results Significant differences of T1 values were found among different pathological types of lung cancer(all P＜0.05),as well as between small cell lung cancer and the rest 2 types of lung cancer(both P＜0.05).There were significant differences of T1 values between poorly differentiated and moderately well differentiated lung cancer(squamous cell carcinoma+adenocarcinoma)(both P＜0.05).Taken ROI1 T1 value=1 524.21 ms as the cut-off value,the AUC of T1 value for distinguishing poorly differentiated and moderately well differentiated lung cancer(squamous cell carcinoma+adenocarcinoma)was 0.698,with sensitivity of 64.50％and specificity of 76.00％.Taken ROI2 T1 value=1 630.68 ms as the cut-off value,the AUC of T1 value was 0.676,with sensitivity of 54.80％and specificity of 80.00％.Conclusion B1 corrected T1 mapping was helpful for distinguishing pathological types and differentiation degrees of lung cancers.

ObjectiveTo explore the possible mechanisms of Shoutai Wan （寿胎丸） in treating recurrent miscarriage （RSA） from the perspective of immune tolerance under the acidic microenvironment at the maternal-fetal interface. MethodsFemale CBA/J mice were randomly divided into normal group， model group， progesterone group， and Shoutai Wan group， with 15 mice in each group. The mice in the normal group and model group were given 0.2 ml distilled water by gavage each day， the Shoutai Wan group given Shoutai Wan decoction 0.15 g/（10 g·d） by gavage， the progesterone group given progesterone tablets 0.44 mg/（10 g·d） by gavage. After gavage for 14 days， the mice were cohabited. Female CBA/J mice in the normal group were mated with male BALB/c mice at a ratio of 2∶1， and female CBA/J mice in the other groups were mated with male DBA/2 mice at a ratio of 2∶1 to establish the RSA mouse model. Vaginal smears were taken from the female mice the next morning， and the appearance of a large number of spermatozoa and the presence of a vaginal plug were considered as the first day of pregnancy. After the appearance of the plug， the mice were continued to be administered according to the previous method until the 10th day of pregnancy. On the 10th day of pregnancy， maternal-fetal interface tissues were collected from each group of mice， and lactate dehydrogenase colorimetric method was used to detect lactate （LA） content； qPCR method and Western blot method were used to detect the expression of immune-related factors interleukin-4 （IL-4）， interferon-gamma （IFN-γ）， transforming growth factor beta 1 （TGF-β1）， and forkhead box protein 3 （Foxp3） mRNA and protein； flow cytometry was used to detect the numbers of helper T lymphocyte 1 （Th1）， helper T lymphocyte 2 （Th2）， regulatory T cell （Treg）， classical macrophage （M1）， and alternative macrophage （M2）. The bivariate Pearson test was used to analyze the correlation between LA content and the numbers of Th1， Th2， Treg， M1， and M2 cells， as well as the correlation between LA content and the expression of IL-4， IFN-γ， TGF-β1， Foxp3 protein， and mRNA. ResultsOn the 10th day of pregnancy， compared with the normal group， the LA content decreased in the model group， and the expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues decreased， while the expression of IFN-γ protein and mRNA increased. The numbers of Th1 and M1 cells increased， while the numbers of Th2， Treg， and M2 cells decreased （P＜0.05 or P＜0.01）. Compared with the model group， the LA content increased in the Shoutai Wan group and progesterone group. The expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues increased， while the expression of IFN-γ protein and mRNA decreased. The numbers of Th1 and M1 cells decreased， while the numbers of Th2， Treg， and M2 cells increased （P＜0.05 or P＜0.01）. The LA content was positively correlated with the numbers of Th2， Treg， and M2 cells， and the expression of IL-4， TGF-β1， Foxp3 protein， and mRNA （P＜0.05 or P＜0.01）； the LA content was negatively correlated with the numbers of Th1， M1 cells， and the expression of IFN-γ protein and mRNA （P＜0.05 or P＜0.01）. ConclusionShoutai Wan may improve immune tolerance by regulating the expression of immune-related factors in the acidic microenvironment at the maternal-fetal interface of RSA model mice， thereby exerting its role in preventing miscarriage.

Objective To investigate the status of occult hepatitis B virus infection(OBI)among blood donors in Quzhou,Zhejiang,and to analyze the mutation of S region in blood donors with anti-HBc+alone and non anti-HBc+alone.Methods The OBI samples were screened by ELISA and NAT;the HBV DNA was amplified and sequenced;20 anti-HBc+alone and 25 not anti-HBc+alone samples were obtained.Results The detection rate of OBI in Quzhou was 0.10%(155/161 045),and the positive rate of anti-HBc was 74.19%(115/155).The detection rate of OBI increased with the age of blood donors(P＜0.05),but was not related to gender.The positive rate of anti-HBc+alone was 22.58%(35/155),and that of not anti-HBc alone was 51.61%(80/155).Among the 45 OBI sequencing samples,the proportion of B and C geno-type was73.33%(33/45)and 20.00%(9/45),respectively.The mutation sites of blood donors in the anti-HBc+alone group were more than those in the not anti-HBc+alone group,and the mutation rates of S114T and V168A on MHR were significantly different(P＜0.05).Conclusion The genotype of OBI infection in Quzhou is mainly type B.The mutation sites of blood donors with anti-HBc+alone are higher than those with not anti-HBc+alone,which may be more suitable as one of the OBI screening indicators.

Objective To investigate the impacts of butorphanol(BUT)on the biological activity and chemotherapy drug resistance of osteosarcoma cells by regulating the forkhead box protein O3(FOXO3)-forkhead box protein M1(FOXM1)signal axis.Methods CDDP resistant MG-63 cells(MG-63/CDDP)treated with 2.0 μmol/L cisplatin(CDDP)were separated into control group(MG-63/CDDP cells were treated with 0.05％DMSO medium),BUT group(MG-63/CDDP cells were treated with 40 μg/mL BUT),JY-2 group(MG-63/CDDP cells were treated with 100 μmol/L FOXO3-FOXM1 inhibitor JY-2),and BUT+JY-2 group(MG-63/CDDP cells were treated with 40 μg/ml BUT and 100 μmol/L JY-2).CCK8 method was applied to detect MG-63/CDDP cell activity.Flow cytometry was used to detect apoptosis in MG-63/CDDP cells.The Transwell method was applied to detect the migration and invasion of MG-63/CDDP cells;Western blot was applied to detect the expression of autophagy proteins and proteins related to the FOXO3-FOXM1 signaling pathway.Results Compared with MG-63 cells,the IC50(20.56±2.52μmol/L vs(0.97±0.10μmol/L)of MG-63/CDDP cells was increased,and the differences was statistically significant(q=19.017,P<0.05),and the optimal concentration of 1 μmol/L CDDP was selected for subsequent experiments.Compared with the control group,the A value(0.43±0.05 vs 0.68±0.06),numbers of cell migration(63.63±7.58 vs 114.56±10.57)and invasion(43.38±4.58 vs 79.56±8.48),and the levels of autophagy-related protein Beclin1(0.31±0.05 vs 0.62±0.07)and microtubule-associated protein light chain 3(LC3)-Ⅱ/Ⅰ proteins(0.51±0.08 vs 0.98±0.11)in the BUT group were reduced(q=6.763～9.591,all P<0.05),the apoptosis rate(28.57％±3.14％vs 8.67％±1.46％),the levels of FOXO3(0.72±0.08 vs 0.33±0.04)and FOXM1(1.22±0.15 vs 0.70±0.08)proteins were increased(q=14.077,10.681,7.493,all P<0.05),however,in the JY-2 group,the A value(0.99±0.13 vs 0.68±0.06),numbers of cell migration(147.59±15.37 vs 114.56±10.57)and invasion(111.83±12.58 vs 79.56±8.48),and the levels of Beclin1(0.94±0.11 vs 0.62±0.07)and LC3-Ⅱ/Ⅰ(1.27±0.13 vs 0.98±0.11)proteins in the JY-2 group were increased(q=4.171～6.012,all P<0.05),the apoptosis rate(4.56％±0.86％vs 8.67％±1.46％),the levels of FOXO3(0.17±0.01 vs 0.33±0.04)and FOXM1(0.46±0.03 vs 0.70±0.08)proteins were reduced(q=5.941,9.505,6.881,all P<0.05),and the differences were statistically significant,respectively.JY-2 reversed the beneficial effects of BUT on MG-63/CDDP cell activity and chemotherapy resistance.Conclusion BUT may regulate the cell activity and CDDP resistance of osteosarcoma cells by activating the FOXO3-FOXM1 signaling pathway.

Objective:To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM).Methods:A retrospective cohort study design was performed . Eight-nine Children diagnosed as TBM during January 1 st 2016 and December 31 st 2023 in Department of Infectious Disease, Children′s Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results:The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions:The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.

Objective To explore the effect of hospital community integration management program on monocyte(MONO),blood uric acid(BUA),body mass index(BMI)and MONO/high density lipoprotein cholesterol ratio(MHR)in patients with hyperuricemia(HUA).Methods A total of 103 HUA patients admitted to the department of nephrology of the First Hospital of Ninghai County from January 2020 to January 2022 were chosen as the study object.The patients were divided into experimental group(51 cases,management method:hospital community integration management mode)and the control group(52 cases,management method:conventional management mode)based on the admission order(odd and even).The differences of MONO,BUA,BMI,MHR between the two groups at admission and discharge and 6,12 and 24 months after discharge were compared,and the occurrence of adverse reactions was observed.Results There were no significant differences in MONO,BUA,BMI and MHR levels at admission between the two groups,MONO,BUA,BMI and MHR levels were significantly lower at discharge and at 6,12,and 24 months after discharge compared with admission.The lowest level was reached 24 months after discharge,and the experimental group was significantly lower than the control group[MONO(×109/L):0.34(0.16)vs.0.37(0.18),BUA(μmol/L):329.7±70.5 vs.381.2±71.7,BMI(kg/m2):21.3±1.1 vs.24.2±0.9,MHR:0.24(0.16)vs.0.27(0.15),all P<0.05].The overall incidence of adverse reactions in the experimental group was significantly lower than that of control group[3.92%(2/51)vs.15.38%(8/52),P<0.05].Conclusion The scientific and reasonable implementation of integrated hospital and community management is beneficial to reduce the levels of MONO,BUA,BMI,MHR and reduce the occurrence of adverse reactions in patients.

Objective:To explore the risk factors of oral-mucosal pressure injury (OMPI) in patients with tracheal intubation in ICU and to establish a nomogram model.Methods:Using the convenient sampling method, a total of 640 patients with oral tracheal intubation admitted to ICU of the First Affiliated Hospital of Xinjiang Medical University from January to May 2023 were selected as the research objects. They were divided into the occurrence group ( n=286) and the non-occurrence group ( n=354) according to whether OMPI occurred or not. Binomial Logistic regression analysis was used to explore the risk factors for OMPI in patients with tracheal intubation in ICU. A risk nomogram model was created based on independent risk factors, and internal verification was conducted by Bootstrap repeated sampling method. Results:OMPI occurred in 286 of 640 ICU patients with tracheal intubation. Binomial Logistic regression analysis showed that high APACHEⅡ score, modified Beck oral score greater than or equal to 11 points, use of sedative drugs, prone ventilation, long retention time of tracheal catheter, low oxygenation index less than 200 mmHg (1 mmHg=0.133 kPa) and tracheal catheter fixation frequency of 1 time /24 h were the risk factors for OMPI in patients with tracheal intubation in ICU ( P<0.05). A risk nomogram model for OMPI in patients with tracheal intubation in ICU was established based on independent risk factors. The results showed that the predictive performance (area under the receiver operating characteristic curve of subjects was 0.918, 95% confidence interval was 0.897 to 0.938) and calibration (χ 2 value of 4.647, P=0.795) of the risk nomogram model for OMPI in patients with tracheal intubation in ICU were good. When the threshold probability was 0 to 1, the decision curve showed that the model had good clinical effectiveness. Conclusions:The OMPI risk nomogram model of tracheal intubation patients in ICU established in this study has good calibration and differentiation, which can be used as an effective tool for screening high-risk patients.