Separation and determination of chiral and achiral impurities in glimepiride tablets by supercritical fluid chromatography. Chiral and achiral impurities were separated on a ACQUITY UPC² Trefoil^TM CEL1 column (150 mm × 3.0 mm, 2.5 μm) maintained at 30 ℃ with the mobile phase containing a mixture of CO₂ and methanol-isopropanol (1∶1) at 1 mL·min^-1, and the detection wavelength was set at 228 nm. The back pressure was set at 13.8 MPa. The injection volume was 5 μL. In the chromatogram of the system suitability solution, the peaks elute in the following order: impurity Ⅳ, impurity Ⅴ, glimepiride, impurity Ⅲ, impurity Ⅰ and impurity Ⅱ. The six substances were separated successfully in 6 min using the proposed method with a resolution factor of 2.9, 1.6, 3.0, 2.0, 6.4. The impurity Ⅰ-Ⅴ detection limit (S/N = 3) was 0.17, 0.10, 0.06, 0.15, 0.10 μg·mL^-1, respectively. Good linear relationship was established between the peak response and the concentration in the range of 0.48-51.30 μg·mL^-1 for all impurities. The spiked recovery of impurity Ⅰ-Ⅴ was found to be acceptable for 99.9%, 98.9%, 102.1%, 100.1%, 96.3% (n = 9), respectively. The related substance and assay results of 11 sample batches are consistent with the results obtained using the HPLC method in the Chinese Pharmacopoeia. Compared to the two HPLC methods in the Chinese Pharmacopoeia, the established supercritical fluid chromatography method can simultaneously separate glimepiride and its 5 impurities in a single run, and it has the following advantages: simplified sample preparation, greatly reducing the volumes of organic solvents, environmentally friendly, high accuracy and good reproducibility. It can be employed for the quality control of the chiral and achiral impurities in glimepiride tablets.

Aim To explore the mechanism of Bushen Tongfu decoction(BSTF)improving the learning and memory ability of APP/PS1 mice.Methods The APP/PS1 mice were administered by BSTF for eight weeks.The spatial learning and memory ability of all mice were detected by Morris water maze.The changes in the intestinal microbiota and gut metabolites of mice were detected by 16S rDNA and LC-MS/MS technolo-gy.Results Compared with the model group,the es-cape latency and swimming path in BSTF-H,BSTF-M and BSTF-L groups were shortened and the times of target crossings after removing the platform increased significantly(P＜0.01).The 16S rDNA results showed that BSTF could increase the abundance of beneficial bacteria of Firmicutes and reduce the abun-dance of harmful bacteria of Bacteroidota in APP/PS1 mice.A total of 25 differential metabolites were identi-fied by LC-MS/MS,including sphingolipid metabo-lism,lysine metabolism and tyrosine metabolism.KEGG enrichment analysis showed that the therapeutic effect of BSTF was mainly through inflammation-related signaling pathways such as NF-κB pathways and Apelin pathways.Conclusions The mechanism of BSTF im-proving the learning and memory ability of APP/PS1 mice may be related to the improvement of intestinal flora composition,the effect of sphingolipid metabo-lism,lysine metabolism and tyrosine metabolism and the regulation of inflammation-related signaling path-ways such as NF-κB and Apelin pathways.

The aim of this study was to investigate the prevalence of spotted fever group rickettsia(SFGR)in wild rodents collected from Fengshan County in the Guangxi Zhuang Autonomous Region,and to determine their species.Wild rodents were captured in cages in Fengshan County,Hechi City,Guangxi Zhuang Autonomous Region.The rodents were identified according to morphological characteristics,and the findings were confirmed through molecular biology methods.Subsequently,spleen samples were collected,and DNA was extracted.The outer membrane protein A(ompA)gene was amplified with semi-nested PCR to determine the species of SFGR in captured wild rodents.After sequencing of the PCR products,homology and phylogenetic analyses of ompA gene sequences were performed.A total of 105 wild rodents belonging to seven species were captured.FGR was detected in six rodent species(Bandicota indica,Leopoldamys edwardsi,Mus caroli,Mus Pahari,Rat-tus andamanensis,and Rattus losea,but not Berylmys bower si),and the total positivity rate was 23.8％.Three Rickettsia species,Candidatus Rickettsia jingxinensis,Rickettsia raoultii,and Rickettsia sibirica,were identified from analysis of the ompA gene sequence.This study revealed the presence of three species of SFGR infecting wild rodents from Fengshan County,Guangxi Zhuang Autonomous Region,thus suggesting that Fengshan County is a natural focus of tick-borne spotted fever.This study highlights the need to strengthen monitoring and prevention measures for rickettsiosis.

Objective:To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid(PUFA)against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice.Methods:The experimental animals were divided into 4 groups:wild-type mice normal control group,mfat-1 transgenic mice normal control group,wild-type mice model group and mfat-1 transgenic mice model group.The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model,while the mice in the normal control group were injected intraperitoneally with an equal amount of saline,and their status was observed and their body weight was measured daily.Peripheral blood was taken after 14 day for routine blood analysis,and the content and proportion of PUFA in peripheral blood were detected using gas chromatography.Bone marrow nucleated cells in the femur of mice were counted.The histopathological changes in bone marrow were observed by histopathological staining.The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR.Results:Compared with wild-type mice,mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin.Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes,erythrocytes,platelets and haemoglobin in peripheral blood of myelosuppressed mice.The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin.Flow cytometry and PCR showed that,compared with wild-type mice model group,the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced(P＜0.001),and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased(P＜0.01),while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced(P＜0.001,P＜0.05).Conclusion:Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells,increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.

BACKGROUND: Primary dysmenorrhea (PD) is the most common complaint associated with menstruation and affects up to three-quarters of women at some stage of their reproductive life. In Chinese medicine, navel therapy, treatment provided at Shenque (CV 8), is used as a treatment option for PD. OBJECTIVE: To evaluate the effect of navel therapy on pain relief and quality of life in women with PD, compared with Western medicine (WM). METHODS: China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), SinoMed and Wanfang Database, MEDLINE, the Cochrane Library, Embase, Web of Science, and the International Clinical Trial Registry of the U.S. National Institutes of Health were searched from their inceptions to April 1, 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of navel therapy on PD were eligible for inclusion. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool. RESULTS: Totally 24 RCTs involving 2,614 participants were identified. Interventions applied to acupuncture point CV 8 included: herbal patching, moxibustion or combined navel therapy (using at least 2 types of stimulation). Compared to placebo, there was a significant effect in favor of navel therapy on reducing overall menstrual symptom scores at the end of treatment [mean difference: -0.82, 95% confidence interval (CI): -1.00 to -0.64, n=90; 1 RCT]. As compared with Western medicine, navel therapy had a superior effect on pain intensity as assessed by Visual Analogue Scale at the end of treatment [standardized mean difference (SMD): -0.64, 95% CI: -1.22 to -0.06, I²=80%, n=262; 3 RCTs]; on symptom resolution rate at 3-month follow-up (risk ratio: 1.94, 95% CI: 1.47 to 2.56, n=1527, I²=38%; 13 RCTs); and on global menstrual symptoms score at the end of treatment (SMD: -0.67, 95% CI: -0.90 to -0.45, I²=63%, n=990; 12 RCTs). Subgroup analyses showed either a better or an equivalent effect comparing navel therapy with Western medicine. No major adverse events were reported. The methodological quality of included trials was poor overall. CONCLUSIONS Navel therapy appears to be more effective than Western medicine in decreasing menstrual pain and improving overall symptoms of PD. However, these findings need to be confirmed by well-designed clinical trials with adequate sample size (Systematic review registration at PROSPERO, No. CRD42021240350).
United States ; Female ; Humans ; Dysmenorrhea/drug therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Moxibustion ; Pain Management

Influenza is an acute respiratory infectious disease caused by influenza virus. Pregnancy is associated with physiologic and immunological changes that may increase the risk for influenza virus infection and influenza-related complications. Influenza vaccination is the most effective way to prevent influenza virus infection. WHO and many countries have classified pregnant women as a priority population for influenza vaccination, however, there are still many challenges for promoting influenza vaccination in pregnant women in China, influenza vaccination coverage in pregnant women remains low and some influenza vaccine package inserts list pregnancy as an absolute contraindication. In this paper, we summarize the research progress in the effects of influenza infection and influenza vaccination during pregnancy both at home and abroad, then discuss the strategies to promote influenza vaccination in pregnancy for the purpose of providing reference for the related research and policy development in China.
Pregnancy ; Female ; Humans ; Pregnant Women ; Influenza, Human/epidemiology* ; Pregnancy Complications, Infectious/epidemiology* ; Influenza Vaccines ; Vaccination ; Orthomyxoviridae

Objective: To analyze the levels and distribution characteristics of blood cadmium and urinary cadmium in American adults, to analyze the relationship between blood cadmium and urinary cadmium and pulmonary function dose response, and to explore the effect of this index on the risk of chronic obstructive pulmonary disease. Methods: In March 2022, 3785 patients from 2007 to 2012 in NHANES database were selected as the subjects. Collect demography data such as gender and age, and test data such as lung function, blood cadmium concentration and Urine cadimium concentration. The relationship between blood and urine cadmium levels and lung function and pulmonary function and chronic obstructive pulmonary diease (COPD) was analyzed by Mann-Whitney U test or Kruskal-Wallis H test, multivariate linear regression and restricted cubic spline method. Results: The geometric mean of blood cadmium and urine cadmium in American adults was 0.37 g/L and 0.28 g/L, FEV(1) and FEV(1)/FVC among different cadmium exposure groups was statistically significant, and there was a negative linear dose-response relationship between serum Cd and urine Cd concentrations and FEV(1)/FVC levels (P(overall)<0.001, P(non-linear)=0.152; P(overall)<0.001, P(non-linear)=0.926). Compared with the lowest quartile concentration (Q1), the highest quartile blood cadmium concentration (Q4) (OR=1.934, P(trend)=0.000) and urinary cadmium concentration (OR=1.683, P(trend)=0.000) may increased the risk of chronic obstructive pulmonary disease. Conclusion: There is a negative correlation between blood cadmium, urinary cadmium levels and lung function in American adults, and cadmium may increase the risk of chronic obstructive pulmonary disease.
Adult ; Humans ; Cadmium ; Nutrition Surveys ; Lung ; Pulmonary Disease, Chronic Obstructive ; Respiratory Function Tests

Objective: To summarize the characteristics of patients with newly diagnosed multiple myeloma (NDMM) admitted at Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine. We compared the clinical characteristics and prognoses among patients with non-extramedullary disease (EMD), bone-related extramedullary (EM-B) disease, and extraosseous extramedullary (EM-E) disease and further explored the effects of autologous hematopoietic stem cell transplantation (ASCT) for EMD. Methods: From January 2015 to January 2022, data of 114 patients (22%) with EMD out of 515 patients with NDMM were retrospectively analyzed; 91 (18%) and 23 (4%) patients comprised the EM-B and EM-E groups, respectively. The clinical characteristics of patients in all groups were compared with the Chi-square test. Progression-free survival (PFS) and overall survival (OS) of patients were analyzed by the Kaplan-Meier method. Independent prognostic factors were determined using multivariate Cox proportional hazard model. Results: There were no significant differences in age, gender, ISS stage, light chain, creatinine clearance, cytogenetic risk, 17p deletion, ASCT, and induction regimens among the three groups. Overall, 13% of EM-E patients had IgD-type M protein, which was significantly higher than that in EM-B patients (P=0.021). The median PFS of patients in the non-EMD, EM-B, and EM-E groups was 27.4, 23.1, and 14.0 months; the median OS was not reached, 76.8 months, and 25.6 months, respectively. The PFS (vs non-EMD, P=0.004; vs EM-B, P=0.036) and OS (vs non-EMD, P<0.001; vs EM-B, P=0.002) were significantly worse in patients with EM-E, while those were not significantly different between patients with EM-B and those with non-EMD. In the multivariate analysis, EM-E was an independent prognostic factor for OS in patients with NDMM (HR=8.779, P<0.001) and negatively impacted PFS (HR=1.874, P=0.050). In those who did not undergo ASCT, patients with EM-B had significantly worse OS than those with non-EMD (median 76.8 months vs. not reached, P=0.029). However, no significant difference was observed in the PFS and OS of patients with EM-B and those with non-EMD who underwent ASCT. Conclusions: Compared to patients with either non-EMD or EM-B, those with EM-E had the worst prognosis. EM-E was an independent risk factor for OS in patients with NDMM. ASCT can overcome the poor prognosis of EM-B.
Humans ; Multiple Myeloma/therapy* ; Retrospective Studies ; China ; Hematopoietic Stem Cell Transplantation ; Prognosis ; Transplantation, Autologous

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging