Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective To analyze the relationship of miRNA-146a gene polymorphisms and ischemic post-stroke depression(PSD).Methods The SNP rs2910164 in the miRNA-146a gene in 200 ischemic PSD patients(case group)and 200 ischemic non-PSD patients(control group)was analyzed using the SNaPshot technique.The relative expression levels of miRNA-146a in the peripheral blood of two groups were determined.Results The case group showed significantly different allele and genotype frequencies of the SNP rs2910164 as compared with the control group(G vs.C:P=0.003;GG+CG vs.CC:P=0.012).Meanwhile,the case group presented a significantly lower level of miRNA-146a relative expression(P<0.05).Within the control group,additionally,the subgroup of GG+CG genotypes demonstrated a significantly lower level of miRNA-146a relative expression compared with the subgroup of CC genotypes(P<0.05).Conclusion SNP rs2910164 in the miRNA-146a is associated with the susceptibility to ischemic PSD,and G allele may play a role in the ischemic PSD.

Allergen immunotherapy（AIT）is currently the etiological treatment for respiratory allergic diseases，which can change the natural course of the disease.However，due to the complexity of patients' autoimmune status，allergy triggers and their complicated relationship with AIT vaccines，there are still about 40% of allergic rhinitis and 10%-20% of asthma patients who respond nonoptimally or even don't show any response to AIT. Thus，searching biomarkers that can evaluate and predict the efficacy of AIT and optimize the AIT strategy has been a major focus and challenge in allergy field.Currently，several serologic biomarkers have been found to be associated with AIT efficacy in vitro，but their value as predictive biomarkers of AIT efficacy needs to be further verified. This article reviews the research progress of serologic candidate biomarkers for AIT efficacy.

Objective:To investigate the effect of bedside high-flow continuous blood purification (CBP) combined with Xuebijing in the treatment of severe sepsis (SS) and the influence on the patient′s coagulation-fibrinolysis index, immunity index and expression of peripheral blood Toll-like receptor 4 (TLR4).Methods:Ninety-three patients with SS who were admitted and treated in the Lianyungang First People′s Hospitalfrom January 2017 to October 2019 were selected. They were divided into the combined group (51 cases, treatment with bedside high-flow CBP and Xuebijing injection based on bundle therapy) and the control group (42 cases, treatment with Xuebijing injection based on bundle therapy). The changes in coagulation and fibrinolysis index, immunity index, biochemical index such as TLR4 before treatment and after 1 week of treatment were compared between the two groups. The incidences of complications in both groups were statistically analyzed, and the discharge time from ICU, mechanical ventilation time and 28-day mortality were recorded.Results:After 1 week of treatment, the levels of prothrombin time (PT) and activated partial thromboplastin time (APTT) in the two groups were shortened, D-dimer (D-D) and fibrinogen (FIB) were decreased ( P<0.05); and the levels of PT and APTT in the combined group were shorter than those in the control group, the levels of DD and FIB were lower than those in the control group, there were statistical differences ( P<0.05). After 1 week of treatment, the levels of CD 4+ and CD 4+/CD 8+ ratio in both groups were increased ( P<0.05), and the levels of CD 4+ and CD 4+/CD 8+ ratio in the combined group were higher than those in the control group ( P<0.05). After 1 week of treatment, the levels of TLR4, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), blood lactate (Lac), blood urea nitrogen (BUN) and serum creatinine (Scr) in both groups were decreased ( P<0.05), meanwhile, the above indexes in the combined group were lower than those in the control group ( P<0.05). The incidence of multiple organ failure and the 28-day mortality rate in the combined group were lower than those in the control group: 3.92%(2/51) vs. 19.05%(8/42), 13.73%(7/51) vs. 30.95%(13/42), there were statistical differences ( P<0.05). The discharge time from ICU and mechanical ventilation time in the combined group were shorter than those in the control group: (12.35 ± 2.14) d vs. (14.17 ± 3.36) d, (7.12 ± 2.23) d vs. (8.51 ± 2.39) d, there were statistical differences ( P<0.05). Conclusions:Bedside high-flow CBP combined with Xuebijing injection in the treatment of SS can improve the patient′s condition, regulate the balance of coagulation and fibrinolysis, avoide the activation of coagulation, inhibite inflammatory response, reduce the expression of TLR4 in peripheral blood, improve immune function, protecte kidney function and promotethe patient′s recovery.

Objective:To compare the effect of two vs one stitch on outcomes in women with cervical incompetence who undergo emergency transvaginal cervical cerclage.Methods:A retrospective study was conducted on 38 cases of cervical incompetence patients who underwent emergency cervical cerclage at Fujian Maternity and Child Health Hospital from January 2018 to December 2022. These subjects were divided into two groups: one stitch group (loop continuous suture and knot at cervical-vaginal junction level) and two stitches group (the first loop was closed with a single suture set, and the second loop was closed below the first loop near the cervical outlet) with 19 cases in each group. Two independent samples t or t'-test, rank-sum test, Chi-square test and Fisher's exact test were used to compare the differences in perinatal outcomes between the two groups. Kaplan-Meier survival analysis was performed to evaluate the efficacy of the prolongation of gestational age after emergency transvaginal cervical cerclage. Results:There was no statistically significant difference in the gestational age at cervical cerclage between the two stitches and the one stitch group [24.9 weeks (23.9-25.9 weeks) vs 23.6 weeks (22.6-24.9 weeks), Z=－1.61, P=0.108]. The average gestational age at delivery [(33.1±4.8) vs (28.6±4.3) weeks, t=－3.10] and the prolongation of gestational age after cerclage[(8.5±4.6) vs (5.0±2.6) weeks, t=－2.90] were significantly greater in the two stitches group compared to those in the one stitch group, while the rates of preterm birth before 32 weeks (6/19 vs 16/19, χ2=10.80), 34 weeks (8/19 vs 17/19, χ2=9.47), and 37 weeks (14/19 vs 19/19, Fisher's exact test) were lower (all P<0.05). The Kaplan-Meier survival analysis demonstrated that the two stitches group had significantly higher efficacy in prolonging gestational age compared to the one stitch group [log-rank test χ2 (1)=13.10, P<0.05]. Although there was no statistically significant difference in the neonatal mortality between the two groups (2/19 vs 4/19, Fisher's exact test, P=0.660), survival neonates in the two stitches group had significantly higher birth weight [2 370.0 g (1 775.0-2 710.0 g) vs 1 300.0 g (1 210.0-1 660.0 g), Z=－3.14], lower admission rate to the neonatal intensive care unit (9/17 vs 15/15, Fisher's exact test), lower incidence of stage Ⅲ necrotizing enterocolitis (0/17 vs 5/15, Fisher's exact test), moderate-severe respiratory distress syndrome (5/17 vs 10/15, χ2=4.44), and grade Ⅲ-Ⅳ intraventricular hemorrhage (0/17 vs 7/15, Fisher's exact test) compared to those in the one stitch group (all P<0.05). Conclusion:Compared with emergency cervical cerclage with one stitch, the procedure with two stitches can prolong the gestational age and improve the neonatal prognosis more effectively.

Objective:To investigate the incidence and risk factors associated with preterm premature rupture of membranes (PPROM) following transvaginal cervical cerclage.Methods:This retrospective cohort study involved 170 singleton pregnancies with cervical incompetence who underwent vaginal cervical cerclage at Fujian Maternity and Child Health Hospital from January 2021 to January 2022. Based on the onset of PPROM after cervical cerclage, the patients were divided into the PPROM group ( n=28) and the non-PPROM group ( n=142). Independent samples t-test, rank-sum test, Chi-square test, or Fisher's exact test were used to compare the general condition, pre- and postoperative data, pregnancy complications or comorbidities between the two groups, with a significance level at α=0.1. Multiple logistic regression analysis was conducted to identify the risk factors for PPROM after cerclage surgery. Results:The overall incidence of PPROM after vaginal cervical cerclage was 16.5% (28/170). Logistic regression analysis showed that a history of cervical conization ( OR=11.966, 95% CI:1.695-84.468), the use of Mersilene RS22 tape as the suture material ( OR=3.318, 95% CI:1.064-9.252), cervical length<2.5 cm after cerclage ( OR=3.486, 95% CI:1.116-10.888), and Mycoplasma genitalium- positive results for cervical secretion culture after surgery ( OR=4.856, 95% CI:1.487-15.861) were the independent risk factors for PPROM after cervical cerclage (all P<0.05). Conclusions:The incidence of PPROM following vaginal cervical cerclage is relatively high and can have unfavorable effects on pregnancy outcomes. Factors such as a history of cervical conization, the use of Mersilene RS22 tape for cerclage, cervical length<2.5 cm after cerclage, and Mycoplasma genitalium-positive results for cervical secretion culture after surgery may increase the risk of PPROM after cerclage.

Objective:To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection.Methods:Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A, n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B, n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results:After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A ( χ 2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% ( χ 2=4.042, P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% ( χ 2=0.992, P=0.319). Conclusions:Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

Objective:To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection.Methods:Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A, n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B, n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results:After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A ( χ 2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% ( χ 2=4.042, P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% ( χ 2=0.992, P=0.319). Conclusions:Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

Post-stroke cognitive impairment （PSCI） refers to a series of syndromes from mild cognitive impairment to dementia caused by stroke. The mitogen-activated protein kinases （MAPK）signaling pathway is a key pathway for transmitting cellular signals in mammals ，and p 38 is a classic branch of it. p 38 MAPK signaling pathway is involved in various pathophysiological processes such as cell growth ，differentiation，apoptosis and inflammatory response in central nervous system diseases. At present ，great progress has been made in clinical and basic experimental studies on prevention and treatment of PSCI by traditional Chinese medicine （TCM），but there is a lack of relevant systematic summary. Therefore ，this article summarizes the role of p 38 MAPK signaling pathway in PSCI and the pharmacological research progress of TCM in prevention and treatment of PSCI through p 38 MAPK signaling pathway.

OBJECTIVE To establish the method for the content determination of ephedrine hydrochloride and pseudoephedrine hydrochloride in Shexiang zhuanggu plaster ，and to evaluate the quality of 222 batches of Shexiang zhuanggu plaster from 41 manufacturers. METHODS HPLC method was established. The determination was performed on Shimadzu Shim-pack GIS-C 18 column with mobile phase consisted of acetonitrile- 0.1％ phosphoric acid （3∶97，V/V）at the flow rate of 0.9 mL/min. The column temperature was set at 30 ℃，the detection wavelength was 210 nm，the sample size was 10 μL. Taking the content data of 222 batches of samples as index ，the cluster heatmap was drawn by Hiplot biomedical data visualization and analysis platform. RESULTS The results of the methodological investigation were in line with the requirements of the general principles stated in 2020 edition of Chinese Pharmacopoeia （part Ⅳ ）. The total contents of ephedrine hydrochloride and pseudoephedrine hydrochloride in 222 batches of samples from 41 manufacturers were 0.646-6.325 μg/cm2. Results of cluster heatmap analysis showed that these samples of 41 manufacturers could be divided into 3 categories. The contents of components in samples from different manufacturers varied greatly ，and the contents of components in different batches of samples from the same manufacturers also varied greatly. If the proposed limit of this product was that the total amount of ephedrine hydrochloride and pseudoephedrine hydrochloride per 1 cm2 would not be less than 1.00 μg，23 of the 222 batches of samples were unqualified. CONCLUSIONS The established method for the content determination of ephedrine hydrochloride and pseudoephedrine hydrochloride in Shexiang zhuanggu plaster is accurate and precise ，and can be used for the quality control. Some manufacturers should pay attention to optimizing production process and strengthening quality control.