ObjectiveTo evaluate the clinical efficacy and safety of the traditional Chinese medicine （TCM） compound Chaiqin Xiaoyong Decoction （柴芩消痈饮， CXD） combined with Jinhuang Ointment （金黄膏， JO） in treating the nodular stage of acne mastitis of liver meridian heat accumulation type. MethodsA randomized， double-blind， placebo-controlled clinical trial was conducted. A total of 108 patients with liver meridian heat accumulation type acne mastitis in the nodular stage were randomly assigned to a treatment group and a control group， with 54 patients in each group. Both groups received topical application of JO once daily at a thickness of 3~5 mm for 8 hours， along with standard nursing care. On this basis， the treatment group received oral CXD granules， while the control group received placebo granules， administered twice daily， 3 sachets per dose， for 14 consecutive days. Clinical efficacy， TCM symptom scores， nodule size， visual analogue scale （VAS） pain scores， white blood cell （WBC） count， C-reactive protein （CRP） level， and systemic immune-inflammation index （SII） were compared. At the end of treatment， efficacy and safety indicators were evaluated. A 6-month follow-up was conducted to compare the proportion of patients undergoing surgical treatment. ResultsThe total clinical efficacy rate in the treatment group was 90.38% （47/52）， significantly higher than 32.00% （16/50） in the control group （P＜0.01）. The treatment group also showed significantly lower TCM symptom scores， VAS scores， nodule size， WBC count， CRP level， and SII （P＜0.05 or P＜0.01）. During follow-up， the surgical intervention rate in the treatment group was 5.77% （3/52）， lower than 14.00% （7/50） in the control group， with a statistically significant difference （P＜0.01）. No significant abnormalities were observed in safety indicators before and after treatment in either group. ConclusionCXD effectively reduces nodule size and alleviates symptoms such as redness and pain in patients with acne mastitis of liver meridian heat accumulation type， improves TCM symptom scores， enhances overall clinical efficacy， and demonstrates good safety.

Objective To explore the carrier rate of thalassemia in Laibin city,Guangxi Province,and provide a theoretical basis for the prevention and control of thalassemia.Methods From January 2020 to December 2021,88 152 patients were screened for thalassemia in the outpatient department of the Women's and Children's Hospital of 4 counties,1 city and 1 district in Laibin by blood cell detection and hemoglobin electrophoresis.The common and rare genes in initially screened positive individuals were detected by gap polymerase chain reaction(Gap-PCR)and reverse dot blot(RBD),and the results were conducted by statistical analysis.Results ① There were 22 553 positive cases in the preliminary screening and 8 327 positive cases received the diagnosis of thalassemia gene.A total of 4 944 thalassemia carriers of thalassemia genes were detected,deducing that the total thalassemia carrier rate in the population of childbearing age in this region was 15.19%,including 3 200 cases of α-thalassemia carriers(64.73%),1 424 cases of β-thalassemia carriers(28.80%),and 320 cases of were carriers α-thalassemia combined with β-thalassemia(6.47%).② There were 3 168 cases of common thalassemia(99.00%)and 32 cases of rare thalassemia(1.00%)among α-thalassemia gene carriers.A total of 13 mutant genes and 34 genotypes were detected,and genotype SEA/αα was the comes first.③ Among the β-thalassemia gene carriers,there were 1 411 cases of(99.09%)common thalassemia and 13 cases(0.91%)of rare thalassemia.A total of 19 mutant genes and 25 genotypes were detected,with CD41-42(-CTTT)being the most common.④ A total of 53 different genotypes were detected in the carriers of α-thalassemia combined with β-thalassemia,and the top genotype was--SEA/αα βCD41-42M/βN.⑤ The carrier rates of Yao and Han nationality were comparable,and the differences were not significant(χ2=0.300,P=0.584).The differences in carrying rates between Zhuang and Yao(χ2=23.66,P＜0.001),and between Zhuang and Han(χ2=116.98,P＜0.001)were significant.⑥ The carrier rate in Xiangzhou County was the highest(20.04%),while the carrier rate in Heshan City was the lowest(12.38%).⑦ The carrier rate of females was higher than that of males,and the difference was significant(χ2=182.03,P＜0.001).Conclusion The variants genotypes of thalassemia in Laibin were complex.This study was the first to investigate the carrier rate and gene mutation spectrum of thalassemia in Laibin Area,which provides valuable baseline data for genetic counseling and prenatal diagnosis.

Objective To explore the effect of Wuwei Xiaoke Formula on intestinal flora and inflammatory factors in patients with type 2 diabetes mellitus.Methods A total of 92 cases of type 2 diabetes patients with Qi-Yin deficiency syndrome were selected and randomly divided into treatment group(n=46)and control group(n=46).The control group was treated with basic treatment + metformin,and the treatment group was treated with Wuwei Xiaoke formula on the basis of the control group.The clinical efficacy,intestinal flora and inflammatory factor levels of the two groups were observed and compared.Results The two groups of patients were evenly distributed,with good baseline status and strong comparability.After treatment,the total effective rate of 91.30%in the treatment group was higher than that of 78.26%in the control group(P<0.05).After treatment,the number of Bacteroides,Lactobacillus and bifidobacterium groups in treatment group was higher than that in control group(P<0.05).The numbers of enterococcus,enterobacter and yeast were lower than those in control group(P<0.05).After treatment,the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and C-reactive protein(CRP)in the treatment group were decreased more significantly than those in the control group(P<0.05).Conclusion Wuwei Xiaoke formula is helpful to improve the clinical symptoms of type 2 diabetes patients,regulate the disorder of intestinal flora in patients,reduce the level of inflammatory factors,and has good safety.

Objective:To investigate the clinical efficacy of labial mucosa graft coupled preputial island flap urethroplasty for recurrent penile curvature after hypospadias repair.Methods:The data of 35 patients with recurrent penile curvature after hypospadias repair who underwent labial mucosa graft coupled preputial island flap urethroplasty in four hospitals from January 2021 to March 2023 were retrospectively reviewed. The median age of the patients was 15(13, 18)years old, five of them had penile dehiscence, and four had urethrocutaneous fistula. All patients received labial mucosa graft coupled preputial island flap urethroplasty, the penile flexion was confirmed by artificial erection test, and the urethra is obliquely cut at the most obvious curvature of the penis. By removing the ventral fibrotic scar tissue, the length of the urethral defect was measured. The urethral plate was reconstructed with the same length of labial mucosa graft and an adjacent preputial island flap was transplanted to cover the reconstructed urethra plate to form a new urethral lumen. The inner urethral stent tube was extracted three days after the operation, and the outer urethral stent tube was removed three weeks after the surgery. Diagnostic urethral exploration was performed 5 weeks post-operation, uroflowmetry examination was performed seven weeks after the procedure, and the perioperative and postoperative follow-up data were analyzed.Results:All patients underwent a successful surgery, with the average duration of the procedure being (114.7±20.1)minutes. After mean follow-up of (15.5±5.9)months, no penile curvature occurred, and 32 patients were successfully repaired. Uroflowmetry examination was achieved in 21 patients at the seventh week after surgery showed their mean maximum flow rate was (18.4±3.7)ml/s. Three cases (8.6%, 3/35) developed urethrocutaneous fistula, who were repaired successfully 6 months after surgery.Conclusions:Utilizing the combination of labial mucosa grafts and preputial island flaps for urethroplasty has been proven to be a reliable and safe option for individuals with recurrent penile curvature following hypospadias repair, with a high success rate and few complications.

Objective To investigate the safety and effectiveness of transumbilical repair for hernia of linea alba within 3 cm above the umbilicus.Methods Clinical data of 26 patients who underwent transumbilical approach hernia repair in our hospital from June 2016 to July 2022 were retrospectively analyzed.Color ultrasound examination showed that the distance from the lower edge of the hernia to the upper edge of the umbilicus was≤3 cm.The hernia repair was performed through the fascial space via the upper edge approach of the umbilical ring.There were 7 boys and 19 girls.The age was 7 months to 11 years old(median,3 years old).The distance from the lower edge of the hernia sac to the upper edge of the umbilicus was(1.46±0.66)cm,and the diameter of the hernia of linea alba was(1.16±0.57)cm.Results The surgery was completed smoothly.The operation time was(39.1±26.3)min.No complication was noted.All the patients were discharged one day after surgery.The follow-ups lasted for 1 year and 2 months to 7 years and 3 months(median,5 years and 1 month).No wound infection,bleeding or other complications occurred.No recurrence of hernia or formation of skin granulomas happened.Conclusion Transumbilical approach repair for hernia of linea alba within 3 cm above the umbilicus is safe and effective,with good cosmetic results.

Objective:To investigate the genetic and evolutionary characteristics of hemagglutinin (HA) and neuraminidase (NA) genes of influenza B/Victoria (BV) virus in Xi′an city from 2019 to 2023.Methods:Twenty-five BV strains isolated from the Xi′an influenza surveillance network laboratory between 2019 and 2023 were collected. The HA and NA genes were sequenced using MiniSeq high-throughput sequencing platform. An evolutionary tree was constructed using bioinformatics software to analyze homology and mutation sites, and to predict N-glycosylation sites online. The antigenicity of the strains was analyzed through hemagglutination inhibition tests.Results:The BV influenza in Xi′an exhibited a distinct seasonal transmission pattern from 2019 to 2023, with peak prevalence occurring during the winter and spring seasons. The evolutionary analysis of the HA genes shows that the strains from Xi′an in 2019 belong to the V1A.3 branch, and the strains from 2021 to 2023 belong to the V1A.3a.2 branch. Analysis of antigenic sites showed that there were variations in 6 sites of 3 antigenic determinants in the HA proteins of the BV strains from 2021-2022 compared to 2019, and 2 sites of 1 antigenic determinant changed in the HA proteins in 2023 compared to 2021-2022. The evolutionary analysis of the NA genes indicates that the BV strains from Xi′an in 2019 belong to the A. 1.1 branch. By 2021 and 2022, it had evolved into the A. 1.2 clade, and by 2023, it had further evolved into the B clade and its derivatives, with no strains showing mutations associated with resistance to NA inhibitors. Antigenic analysis indicated that the majority of BV strains in Xi′an were similar to the strains included in the vaccine composition. Furthermore, glycosylation analysis showed that the potential N-glycosylation sites in the HA proteins of BV strains from 2021-2023 were reduced by one compared to those from 2019, and only a few strains from 2023 displayed alterations in the potential N-glycosylation sites of the NA proteins.Conclusions:The HA and NA genes of the BV strains from 2019 to 2023 are continuously mutating and evolving into new branches. Since 2021, V1A.3a.2 has become the dominant evolutionary branch of the HA genes, while the evolutionary branches of the NA genes from 2019 to 2023 have been continuously changing.

Background::Whether functional gastrointestinal disorders (FGIDs) are associated with the long-term risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association.Methods::About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included. Participants with FGIDs (including irritable bowel syndrome [IBS], dyspepsia, and other functional intestinal disorders [FIDs; mainly composed of constipation]) were the exposure group, and non-FGID participants were the non-exposure group. The primary outcome was incident CKD, ascertained from hospital admission and death registry records. A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD, and the mediation analysis was performed to investigate the mediation proportions of mental health.Results::At baseline, 33,156 (8.0%) participants were diagnosed with FGIDs, including 21,060 (5.1%), 8262 (2.0%), and 6437 (1.6%) cases of IBS, dyspepsia, and other FIDs, respectively. During a mean follow-up period of 12.1 years, 11,001 (2.6%) participants developed CKD. FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.28–1.44). Similar results were observed for IBS (HR, 1.27; 95% CI, 1.17–1.38), dyspepsia (HR, 1.30; 95% CI, 1.17–1.44), and other FIDs (HR, 1.60; 95% CI, 1.43–1.79). Mediation analyses suggested that the mental health score significantly mediated 9.05% of the association of FGIDs with incident CKD and 5.63–13.97% of the associations of FGID subtypes with CKD. Specifically, the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD.Conclusion::Participants with FGIDs had a higher risk of incident CKD, which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8+GZMB+T cells and the decrease of CD8+PD-1+T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.

OBJECTIVE To study the differences in toxicity between intravenous(iv)administration and aqueous solution exposure of Dichroa alkali salt(DAS)in zebrafish.METHODS ① Well-devel-oped zebrafish larvae of 2 d post fertilization(2 dpf)were randomly divided into the normal control(no treatment),solvent control(saline,iv),and DAS groups(0.125,0.25,0.50,1.00 and 2.00 mg·kg-1,iv)before being observed for 3 consecutive days after administration.A heart rate of 0 was determined as death of zebrafish,and the mortality rate,maximum non-lethal dose(MNLD),and 10 percent lethal dose(LD10)were calculated.The incidence of venous sinus congestion,pericardial edema,slowing heart rate and blood flow of zebrafish in the 0.50 and 2.00 mg·kg-1 groups were observed and calculated by somatoscopic microscopy at 4 h after drug administration.Zebrafish larvae were iv given DAS at doses of 0.041,0.136,0.412,and 0.452 mg·kg-1 while the malformation phenotypes of zebrafish larvae development were observed under a stereomicroscope for 3 consecutive days,including pericardial edema,abnormal heart rate,slow blood flow,loss of circulation,eye abnormalities,brain malforma-tions,jaw abnormalities,loss/degeneration of the liver,delayed yolk sac absorption,intestinal abnormal-ities,abnormal body coloration,body edema,curvature of the trunk/tail/nodal cord and muscle degener-ation before the incidence was calculated.②Zebrafish larvae were randomly divided into a normal control group and DAS aqueous solution exposure groups at concentrations of 2.5,5.0,10.0,25.0,50.0,75.0,and 100.0 mg·L-1,observed for 3 d until the mortality rate,LD10,and MNLD were calculated.Zebrafish were exposed to DAS aqueous solutions at concentrations of 0.32,1.06,3.20,and 11.00 mg·L-1,and the malformation phenotypes of zebrafish larvae development were observed under a stereomicro-scope for 3 consecutive days to calculate the incidence.RESULTS ① The MNLD and LD10 of DAS iv administered to zebrafish larvae were 0.412 and 0.452 mg·kg-1,respectively.Compared with the solvent control group,4 h after DAS iv administration,the incidence of sinus congestion,slow heart rate and pericardial edema in the 0.50 and 2.00 mg·kg-1 groups significantly increased(P<0.05,P<0.01),so was the incidence of slow blood flow in the 2.00 mg·kg-1 group(P<0.01).The rate of delayed yolk sac absorption was significantly increased in the 0.041,0.136,0.412,and 0.452 mg·kg-1 groups(P<0.05,P<0.01),so was the mortality rate in the 0.452 mg·kg-1 group(P<0.05),with pericardial edema observed in the dead zebrafish.② The MNLD and LD10 of DAS aqueous solution exposure for zebrafish larvae were 3.20 and 11.00 mg·L-1,respectively.Compared with the normal control group,the incidence of decreased heart rate and slow blood flow was significantly increased in the 3.20 and 11.00 mg·L-1 groups(P<0.01),so was the incidence of significantly darkened intestines in the 1.06,3.20,and 11.00 mg·L-1 groups(P<0.01).The incidence of delayed yolk sac absorption was significantly increased in the 0.32,1.06,3.20,and 11.00 mg·L-1 groups(P<0.05,P<0.01),so was the incidence of trunk curvature and lower jaw malformation in the 11.00 mg·L-1 group(P<0.01).CONCLUSION The toxic phenotypes of DAS are different between iv administration and aqueous solution exposure in zebrafish larvae.DAS aqueous solution exposure can not only lead to slow heart rate,slow blood rheology,delayed yolk sac absorption and intestinal blackening,but also induce neurodevelopmental toxicity.However,iv adminis-tration can effectively ward off significant gastrointestinal damage and neurodevelopmental toxicity.