Objective: To investigate the microbial mechanisms of Banxia Xiexin Decoction (半夏泻心汤, BXXXD) in the treatment of esophageal precancerous lesions. Methods: A total of 30 specific pathogen-free (SPF) grade female C57BL/6J mice were randomly assigned to a control group (n = 6) and a 4-nitroquinoline 1-oxide (4-NQO)-exposed group (n = 24). Esophageal precancerous lesions were induced by providing the 4-NQO-exposed group with 4-NQO in drinking water (100 μg/mL) for 17 consecutive weeks, whereas control group received sterile drinking water. After model establishment, the mice in 4-NQO-exposed group were further randomized into model group and three BXXXD-treated groups: low-dose (BXXXD-L, 3.7 g/kg), medium-dose (BXXXD-M, 7.4 g/kg), and high-dose (BXXXD-H, 14.8 g/kg) groups (n = 6 per group). During the subsequent intervention period, mice in control and model groups were gavaged with sterile water, while mice in BXXXD groups were gavaged once daily with the corresponding dose of BXXXD aqueous extract for 4 weeks. Histopathological changes in esophageal tissues were observed by hematoxylin and eosin (HE) staining. The fecal and esophageal microbiota were profiled via 16S rDNA high-throughput sequencing to evaluate bacterial diversity, community structure, and co-occurrence networks. BXXXD chemical fingerprints were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole QExactive Orbitrap mass spectrometry (UHPLC-QE-MS). Serum short-chain fatty acids (SCFA) level was quantified by targeted metabolomics using gas chromatography-mass spectrometry (GC-MS). Transcriptomic analysis of esophageal tissues was performed to assess gene expression profiles. Results: Compared with model group, BXXXD-M group exhibited reduced mucosal hyperplasia and more orderly epithelial cell arrangement, with superior therapeutic effects in comparison with both BXXXD-L and BXXXD-H groups (P < 0.01). Microbiota analysis revealed that BXXXD increased the abundance of beneficial Enterococcus and reduced pathogenic Escherichia-Shigella in the esophagus. In the gut, BXXXD elevated the relative abundance of beneficial taxa, including Lactobacillus, Dubosiella, Bacteroides, and Faecalibacterium. Targeted metabolomics showed that BXXXD significantly reduced total serum SCFA level (P < 0.01). Transcriptomic analysis indicated that BXXXD downregulated the expression of genes associated with the progression, migration, and invasion of esophageal cancer, which were identified as kallikrein-related peptidase 6 (Klk6), defensin beta 4 (Defb4), family with sequence similarity 3 member B (Fam3b), carboxypeptidase A4 (Cpa4), serum amyloid A1 (Saa1), and chitinase-like 1 (Chil1) (P < 0.05). Conclusion BXXXD may reduce the expression levels of esophageal cancer-related genes and improve esophageal precancerous lesions through modulation of the gut microbiota and metabolites.

ObjectiveTo investigate the efficacy of sequential tenofovir alafenamide fumarate （TAF） therapy versus the regimen of entecavir （ETV） combined with TAF in chronic hepatitis B （CHB） patients experiencing low-level viremia （LLV） after ETV therapy， as well as their impact on virologic response， liver and renal function， and blood lipid levels. MethodsA total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled， and according to the treatment regimen， they were divided into TAF group （180 patients receiving sequential TAF therapy） and combined group （37 patients receiving ETV+TAF therapy）. The propensity score matching （PSM） method was used to match the patients at a ratio of 1∶1， and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA （HBV DNA） clearance rate， hepatitis B envelope antigen （HBeAg） clearance rate， liver and renal function parameters （liver stiffness measurement ［LSM］， platelet count ［PLT］， aspartate aminotransferase ［AST］， alanine aminotransferase ［ALT］， and creatinine ［Cr］）， blood lipid levels （total cholesterol ［TC］， triglyceride ［TG］， high-density lipoprotein cholesterol ［HDL-C］， and low-density lipoprotein cholesterol ［LDL-C］）， and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the paired t-test was used for comparison within each group； the chi-square test was used for comparison of categorical data between groups. ResultsAfter 48 weeks of treatment， compared with the TAF group， the combined group had significantly higher HBV DNA clearance rate （86.49% vs 59.46%， χ²=6.852， P=0.009） and HBeAg clearance rate （59.46% vs 35.14%， χ²=4.391， P=0.036）. After treatment， compared with the TAF group， the combined group had significantly lower levels of LSM （7.01±1.50 kPa vs 7.90±1.68 kPa， t=2.404， P=0.019）， AST （18.02±2.28 U/L vs 21.12±2.85 U/L， t=5.166， P<0.001）， and ALT （19.85±3.86 U/L vs 22.00±3.90 U/L， t=2.383， P=0.020） and significantly higher levels of PLT ［（218.35±42.60）×10⁹/L vs （192.82±44.13）×10⁹/L， t=2.532， P=0.014］ and Cr （70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L， t=2.253， P=0.027）. After treatment， there was a slight increase in the level of TC in both the TAF group （5.60±0.89 mmol/L vs 5.18±0.85 mmol/L， t=2.076， P=0.041） and the combined group （5.45±0.80 mmol/L vs 5.02±0.83 mmol/L， t=2.269， P=0.026）. There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group （21.62% vs 18.92%， χ²=0.084， P=0.772）. ConclusionFor ETV-treated CHB patients experiencing LLV， compared with sequential TAF therapy， the ETV+TAF combined therapy can effectively increase virologic response rate， alleviate liver fibrosis， and improve liver function， whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC， which should be taken seriously in clinical practice.

Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

Objective To explore the neuroprotective effects of osteocalcin(OCN)on an Alzheimer's disease(AD)cell model and its potential mechanisms,providing a scientific basis for new therapeutic targets for AD.Methods Human neuroblastoma cell line SH-SY5Y was treated with 40 nmol/L okadaic acid(OA)for 24 h to establish an AD cell model.The cells were divided into a normal group(untreated SH-SY5Y cells),a model group(40 nmol/L OA intervention),and an OCN intervention group(intervention with various concentrations of OCN in the AD cell model),and AKT knockout/overexpression groups(AKT-KO group and AKT-OE group),and AKT-KO OCN group and AKT-OE OCN group.CCK-8 assay was used to detect the changes in cell viability.Wright's staining was employed to observe the morphological changes of AD cells.Western blotting was utilized to detect the protein levels of Tau,p-Tau,Bax,Bcl-2,Caspase-3 and their lytic types,as well as the expression of Tau,p-Tau,mTOR,AKT and p-AKT in each group after AKT knockout/overexpression.TUNEL staining and flow cytometry were applied to detect the changes in early and late apoptotic cells and the apoptotic rate in the OCN-treated AD cell model.Results ①Compared to the normal group,the model group exhibited a significant decrease in cell viability,noticeable morphological and structural damage,upregulation of p-Tau and Caspase-3,increased early and late apoptosis,and a significantly higher apoptotic rate(P<0.05).②After treatment of different concentrations of OCN for 24 h,cell viability was increased to varying degrees compared to the AD model group,with the 100 pg/mL OCN group showing a significant increase in cell viability(P<0.01)and marked improvement in cell number and morphology(P<0.01).③ Compared to the AD cell model group,the p-Tau/Tau ratio was decreased in all OCN treatment groups,particularly in the 100 pg/mL OCN intervention group,where the p-Tau/Tau ratio was significantly lower than that of the model group(P<0.01).④ Compared to the model group,a significant concentration-dependent decrease in the Cleaved Caspase-3/Caspase-3 ratio was observed when OCN concentrations ranged from 1 to 100 pg/mL,with a significant reduction in the Bax/Bcl-2 ratio in the 100 pg/mL group(P<0.000 1).⑤ The results of TUNEL staining and flow cytometry showed that,compared to the model group,all concentrations of OCN effectively inhibited the apoptosis in the AD model cells,with a significant reduction in early and late apoptotic cells and apoptotic rate in the 100 pg/mL OCN group.⑥ Compared with the control group and the model group,the P-AKT was significantly increased in the AKT-OE group after AKT overexpression(P<0.05).The expression level of AKT protein was decreased in the AKT-KO group after AKT knockout(P<0.05).When the AKT pathway was inhibited,the expression level of p-Tau was higher in the AKT-KO group than the control group(P<0.05),and when the AKT was overexpressed,the expression level was significantly inhibited(P<0.05).Conclusion OCN may inhibit cell apoptosis and reduce p-tau protein level by regulating the ratio of Caspase-3/Caspase-3 and Bax/Bcl-2,and thereby improve the morphology of AD model cells and effectively protect nerve cells,which may be related to the regulation of the AKT/mTOR pathway.

Objective To investigate the association between the variability of remnant cholesterol inflammatory index(RCII),a novel composite biomarker,and the risk of stroke,in order to provide a theoretical basis for stroke prevention.Methods A prospective cohort study was conducted on 38 659 Kailuan individuals who took annual physical examinations in 2006,2008,and 2010.These subjects were grouped based on the quartiles of RCII variability,which was represented by standard deviation(SD)and average real variability(ARV),and were followed up every 2 years,with the occurrence of stroke(including ischemic and hemorrhagic strokes),death,or the end of follow-up on December 31,2022 as the endpoints.Kaplan-Meier method was used to calculate the cumulative incidence rate of endpoint events across different groups,and log-rank test was used to compare the difference of cumulative incidence of endpoint events in each group.Multivariate Cox proportional hazards regression model was adopted to analyze the association between RCII variability and risk of stroke.Results Among the 38 659 participants,a total of 2 539 strokes occurred during a mean follow-up period of 11.22±2.26 years.After adjusting confounding factors,when the participants were grouped by the quartiles of RCII-SD,the hazard ratio(HR)for stroke was 1.034(95%CI:0.917～1.167,P=0.584),1.146(95%CI:1.018～1.290,P=0.025),and 1.209(95%CI:1.066～1.370,P=0.003),respectively in the Q2,Q3,and Q4 groups,when compared with the Q1 group(Ptrend<0.05).When they were grouped by the quartiles of RCII-ARV,the HR for stroke was 1.008(95%CI:0.894～1.136,P=0.901),1.109(95%CI:0.986～1.248,P=0.085),and 1.152(95%CI:1.018～1.303,P=0.025),respectively,in the Q2,Q3,and Q4 groups,when compared with the Q1 group.Furthermore,both sensitivity and stratified analyses yielded similar results.Conclusion RCII variability is significantly associated with stroke,and the risk of stroke is gradually increasing with increment of the variability.Countermeasures Relevant authorities can focus on reducing RCII variability as a central objective by establishing regular monitoring mechanism,strengthening lifestyle interventions,and standardizing dietary,exercise,and weight management in order to suppress the index fluctuations.The principle of stable lipid-lowering in medication and optimization of therapeutic regimens with stable efficacy should be emphasized to prevent the risk of additional vascular damage.

After the wooden shipwreck was recovered from the marine underwater environment,the wooden components undergo varying degrees of degradation,therefore,accurately determining the extent of degradation is a fundamental scientific issue for implementing effective preservation strategies.In this work,the wooden remains of Pinus massoniana excavated from the"Nanhai No.1"shipwreck(Southern Song Dynasty)were investigated and compared with the modern wood to discriminate the degradation levels of archaeological wood using attenuated total reflection Fourier transform infrared(ATR-FTIR)spectroscopy.The residual sugar content within wood cell walls was determined using a non-invasive automated microscale ATR-FTIR method to extract chemical information from the wood tangential section.Microstructural characterization of wood samples was conducted by super depth of field microscopy and scanning electron microscopy.FTIR spectral analysis was performed to evaluate the degradation state and elucidate changes in cellulose crystallinity.Finally,the combination of FTIR spectroscopy with the sparse partial least squares discriminant analysis(sPLS-DA)model facilitated the rapid discrimination of degradation levels in shipwreck archaeological wood,and the performance of the model was evaluated using receiver operating characteristic(ROC)curves and area under the curve(AUC).The results showed that the higher the degree of wood degradation,the lower the residual sugar content in the wood cell wall,and the residual glucose content of highly degraded wood was only 4.7％.Significant differences were observed in both the tangential section microstructure and FTIR characteristic absorption patterns across degradation levels,and as the degradation advanced,progressive cell wall loosening occurred alongside selective removal of polysaccharide components,and the relative lignin content was increased,resulting in an elevated A1509/A1370 ratio in FTIR spectra.The sPLS-DA model achieved excellent discrimination performance with AUC values exceeding 0.9,confirming that the combination of FTIR spectroscopy with sPLS-DA enabled accurate assessment of degradation levels in shipwreck archaeological wood.This study developed a rapid and accurate methodology for assessing degradation levels in shipwreck archaeological wood based on microscale ATR-FTIR spectroscopy,which would help to promote the accurate assessment of the preservation state of waterlogged wooden artifacts.

Objective To investigate the association of neuregulin 4(NRG4)and meteorin-like protein(Metrnl)with insulin resistance in patients with metabolic syndrome(MS).Methods From September to November 2023,totally 60 MS patients in Anhui No.2 Provincial People's Hospital were selected as MS group,and 60 physical examination healthy people were selected as control group.The changes of human mor-phological indicators,biochemical indicators,blood routine,NRG4,Metrnl,insulin resistance index(HOMA-IR)and other indicators in the two groups were observed,and the correlation between NRG4,Metrnl and HO-MA-IR and each index was analyzed,and the diagnostic value of NRG4 and Metrnl for MS was evaluated.Re-sults Compared with the control group,the levels of white blood cell count(WBC),alanine aminotransferase(ALT),uric acid(UA),triglyceride(TG),total cholesterol(TC),fasting insulin(FINS),HOMA-IR,body weight,body mass index(BMI),waist circumference,hip circumference,waist-hip ratio(WHR),and body fat ratio were significantly increased in MS group(P<0.05),however,high density lipoprotein cholesterol(HDL-C),NRG4,and Metrnl were significantly decreased(P<0.05).Spearman correlation analysis showed that serum NRG4 was positively correlated with Metrnl and HDL-C(P<0.05),and negatively correlated with TG,FINS,HOMA-IR,body weight,waist circumference,hip circumference,WHR,and ALT(P<0.05).Serum Metrnl was positively correlated with NRG4 and HDL-C(P<0.05),and negatively correlated with TG and hip circumference(P<0.05).Binary Logistic regression analysis showed that NRG4 and Metrnl were protective factors for MS(P<0.05).The receiver operating characteristic curve analysis showed that the sensitivity of NRG4,Metrnl,and their combination for diagnosing MS was 67%,41%,and 67%,respec-tively,the specificity was 71%,95%,and 86%,respectively,and the area under the curve was 0.713,0.635,and 0.787,respectively.Conclusion The levels of serum NRG4 and Metrnl are decreased in MS patients,and NRG4 is associated with insulin resistance.The combination of NRG4 and Metrnl has a certain diagnostic val-ue for MS.

Ureteropelvic junction obstruction, as a common urological disorder, not only affects the renal function of patients, but also seriously reduces their quality of life. Pyeloplasty, as the first-line therapy for ureteral stricture at present, is a key approach to eliminating hydronephrosis and improving renal function. The quality of life of postoperative patients, as an important criterion for measuring the therapeutic effect, has also attracted increasing attention. Therefore, this article reviews the evaluation tools, research status and influencing factors of the postoperative quality of life of ureteropelvic junction obstruction patients, aiming to provide a reference for the formulation of relevant nursing intervention measures in clinical practice.

Objective:To explore the effects of Qingre Qudu Decoction for fumigation combined with three-gap drainage on wound healing and serum inflammatory factors in patients with acute perianal abscess.Methods:Randomized controlled trial was conducted. A total of 117 patients with acute perianal abscess in the hospital were enrolled as the observation objects between August 2022 and May 2024. According to random number table method, they were divided into observation group (59 cases) and control group (58 cases). Both groups received three-gap drainage therapy. On basis of three-gap drainage, control group was given potassium permanganate, while observation group was given Qingre Qudu Decoction for fumigation. All patients were treated for 14 d. The growth of granulation tissue and wound secretions before and after treatment was evaluated. VAS scale was used to evaluate the degree of incision pain, and Wexner score was used to assess incontinence; ELISA was used to detect serum activator A (ACTA), immunoturbidimetry was used to detect serum CRP, and radioimmunoassay was used to detect serum IL-6 levels. The occurrence of complications and abscess recurrence during treatment was recorded, and clinical efficacy was evaluated.Results:The total effective rate of the observation group was 96.61% (57/59), while that of the control group was 82.76% (48/58), with statistical significance ( χ2=6.10, P=0.014). After treatment, scores of granulation tissue growth and wound secretions in observation group, and scores of VAS and Wexner incontinence in observation group were lower than those in the control group ( t=9.66, 5.00, 7.98, 3.65, P<0.001), and wound healing time was shorter than that in control group ( t=8.41, P<0.001). After treatment, levels of serum ACTA, CRP and IL-6 in observation group were lower than those in control group ( t=15.30, 2.08, 19.34, P<0.01 or P<0.05). The incidence of postoperative complications in the observation group was 6.78% (4/59), while in the control group it was 27.59% (16/58), with statistical significance ( χ2=8.93, P=0.003). Conclusion:Qingre Qudu Decoction for fumigation combined with three-gap drainage can relieve postoperative incision pain, inhibit inflammatory response, accelerate the recovery of wound and promote the recovery of anal function and improve clinical efficacy.

Objective To observe the clinical efficacy of Xiaoyu Sanjie Prescription,which is derived from classical prescriptions Chaihu Guizhi Ganjiang Tang and Huoluo Xiaoling Dan,in treating middle-risk lung nodules of phlegm blended with blood stasis type.Methods A total of 104 cases of patients with middle-risk lung nodules of phlegm blended with blood stasis type who met the inclusion criteria were randomly divided into the trial group and the control group,with 52 cases in each group.Eventually,a total of 97 cases completed the trial for epidemic outbreak,of which 48 cases were in the trial group and 49 cases were in the control group.Both groups received health training,and then the control group was only given regular follow-up,while the trial group was treated with Xiaoyu Sanjie Prescription orally.The course of treatment covered three months.The changes in traditional Chinese medicine(TCM)syndrome scores and the area of maximum lung nodule of patients in the two groups before and after treatment were observed.After treatment,overall TCM syndrome efficacy and overall western medicine efficacy as well as their efficacies for various nodules types in the two groups were assessed.Results(1)After treatment,the distribution of the grade of TCM syndrome scores in the trial group was improved significantly when compared with that before treatment(P<0.01),while that in the control group showed no significant improvement(P>0.05),and the intergroup comparison after treatment showed that the improvement in the trial group was significantly superior to that in the control group(P<0.01).(2)The total effective rate of overall TCM syndrome efficacy in the trial group was 81.25%(39/48),and that in the control group was 20.41%(10/49);the intergroup comparison(tested by rank sum test)showed that the overall TCM syndrome efficacy in the trial group was significantly superior to that in the control group(P<0.01).In terms of the efficacy for various nodule types,the trial group had stronger TCM syndrome efficacy for multiple nodules,mixed solid nodules,pure ground glass nodules and solid nodules than the control group,in particular the efficacy for multiple nodules and mixed solid nodules,and the differences were all statistically significant(P<0.05 or P<0.01).(3)After treatment,the area of the maximum lung nodule in the trial group was significantly reduced(P<0.01),whereas there was no significant reduction in the control group compared with that before treatment(P>0.05).Statistically significant difference was shown in the post-treatment area between the two groups and in the pre-and post-treatment difference of the area between the two groups(P<0.05 or P<0.01),which suggested that the trial group's effect on the reduction of maximum lung nodule area was significantly superior to that of the control group.(4)With regard to the efficacy of western medicine,on the whole,the total effective rate of overall western medicine efficacy in the trial group was 45.83%(22/48),while that in the control group was 6.12%(3/49),and the intergroup comparison(tested by rank sum test)showed that the overall western medicine efficacy in the trial group was significantly superior to that in the control group(P<0.01).The western medicine efficacy for multiple nodules in the trial group was superior to that in the control group(P<0.01),while no statistically significant difference was presented in western medicine efficacy for mixed solid nodules,solid nodules,and pure ground glass nodules between the two groups(P>0.05).Conclusion Xiaoyu Sanjie Prescription is effective on relieving the clinical symptoms of patients with middle-risk lung nodules of phlegm blended with blood stasis type,and is effective on stabilizing,reducing or even eliminating some of the lung nodules.The compatibility principle of the formula deserves further discussion.