Objective:To investigate the clinical characteristics and prognostic significance of germline mutations in patients with myelodysplastic neoplasms (MDS) .Methods:Clinical data from 407 patients with MDS [male, 252; female, 155; median age, 64 (range, 19-85) years] diagnosed at the First Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The clinical features and prognostic effects of germline mutations were evaluated.Results:The prevalence of germline mutations in patients with MDS was 5.9% (24/407), peaking at 20.0% in the group aged 21-30 years. The spectrum of germline mutations comprised DDX41 (9 cases, 2.2%), TP53 (3 cases, 0.7%), and single cases of RUNX1, TET2, MPL, CBL, ATRX, CEBPA, ETV6, IDH1, KDM5C, SBDS, GNAS, and CTC1. Patients with germline mutations exhibited significantly lower peripheral WBC counts than those without (1.87×10 9/L vs 2.50×10 9/L, P=0.018), but showed comparable median overall survival (21.3 months vs 21.1 months, P=0.97). Patients with DDX41 germline mutations, compared with those with other germline mutations, had a significantly older median age (65 vs 54 years, P=0.010), lower WBC counts (1.51×10 9/L vs 2.31×10 9/L, P=0.040), increased mean corpuscular volume (111.80 fl vs 97.25 fl, P=0.003), and a higher prevalence of normal karyotypes (100.0% vs 53.3%, P=0.022). The most frequently co-occurring somatic mutations in DDX41 germline mutation carriers were ASXL1, TET2, and RUNX1. Conclusion:In this study, the detection rate of germline mutations in MDS patients was 5.9% (24/407), peaking at 20% in the group aged 21-30 years. DDX41 and TP53 were the most prevalent germline mutations. DDX41 mutation carriers displayed distinct clinical characteristics; however, germline mutations overall showed no significant prognostic effect.

Objective To establish a rat model of ovarian endometriosis(EMS)using the horn reversion method,to provide an ideal animal model for exploring the pathogenesis and treatment of EMS.Methods Fifty SPF-grade female SD rats were divided randomly into five groups:a sham group,and 1,2,3,and 4 weeks after surgery groups,respectively(n=10 rats per group).Apart from the sham group,an ovarian-type EMS model was established in the other groups by the uterine horn refracture method,and the modeling success rate,and ectopic foci volume and mass were observed in each group.The morphology of ectopic foci was observed by hematoxylin-eosin(HE),and expression of proliferating cell nuclear antigen(PCNA),Ki67,epithelial cadherin(E-cadherin),and neural cadherin(N-cadherin)in the uterus and ectopic foci tissues were detected by immunohistochemistry.The model was further evaluated and the degree of cell proliferation and epithelial mesenchymal transformation at different times after modeling were analyzed.Results The modeling success rates in the 1,2,3,and 4 weeks after surgery groups were 80%,90%,100%,and 100%,respectively(P＞0.05).The volume and mass of the ectopic foci were significantly greater in the 3 and 4 weeks after surgery groups compared with the 1 and 2 weeks after surgery groups(P＜0.01).HE staining showed endometrial epithelial cells,mesenchymal cells and a few glands in the ectopic foci tissues.Immunohistochemical staining showed that expression levels of Ki67,PCNA,and N-cadherin in uterus tissues were significantly higher(P＜0.05,P＜0.01)in all the model groups compared with the sham group,while expression levels of E-cadherin were significantly lower(P＜0.05,P＜0.01).Expression levels of Ki67,PCNA,and N-cadherin in the uterus and ectopic foci tissues were significantly higher(P＜0.05,P＜0.01)in the 2,3,and 4 weeks after surgery groups compared with the 1 week after surgery group,while expression levels of E-cadherin were significantly lower(P＜0.05,P＜0.01).Conclusion The uterine horn reversion method can be used to establish an ovarian EMS model in rats.Ectopic lesions can be observed 1 week after surgery.The success rate of modeling increases with modeling time,stabilizing at 3 weeks postoperatively.Ki67,PCNA,and N-cadherin were significantly expressed in the uterus and ectopic foci tissues,and their expression levels increased with modeling time,while E-cadherin expression in the uterus and ectopic foci tissues decreased with modeling time.These results showed good modeling success of the EMS rat model,suggesting that it could be used as a stable EMS modeling method.

Objective To establish a rat model of ovarian endometriosis(EMS)using the horn reversion method,to provide an ideal animal model for exploring the pathogenesis and treatment of EMS.Methods Fifty SPF-grade female SD rats were divided randomly into five groups:a sham group,and 1,2,3,and 4 weeks after surgery groups,respectively(n=10 rats per group).Apart from the sham group,an ovarian-type EMS model was established in the other groups by the uterine horn refracture method,and the modeling success rate,and ectopic foci volume and mass were observed in each group.The morphology of ectopic foci was observed by hematoxylin-eosin(HE),and expression of proliferating cell nuclear antigen(PCNA),Ki67,epithelial cadherin(E-cadherin),and neural cadherin(N-cadherin)in the uterus and ectopic foci tissues were detected by immunohistochemistry.The model was further evaluated and the degree of cell proliferation and epithelial mesenchymal transformation at different times after modeling were analyzed.Results The modeling success rates in the 1,2,3,and 4 weeks after surgery groups were 80%,90%,100%,and 100%,respectively(P＞0.05).The volume and mass of the ectopic foci were significantly greater in the 3 and 4 weeks after surgery groups compared with the 1 and 2 weeks after surgery groups(P＜0.01).HE staining showed endometrial epithelial cells,mesenchymal cells and a few glands in the ectopic foci tissues.Immunohistochemical staining showed that expression levels of Ki67,PCNA,and N-cadherin in uterus tissues were significantly higher(P＜0.05,P＜0.01)in all the model groups compared with the sham group,while expression levels of E-cadherin were significantly lower(P＜0.05,P＜0.01).Expression levels of Ki67,PCNA,and N-cadherin in the uterus and ectopic foci tissues were significantly higher(P＜0.05,P＜0.01)in the 2,3,and 4 weeks after surgery groups compared with the 1 week after surgery group,while expression levels of E-cadherin were significantly lower(P＜0.05,P＜0.01).Conclusion The uterine horn reversion method can be used to establish an ovarian EMS model in rats.Ectopic lesions can be observed 1 week after surgery.The success rate of modeling increases with modeling time,stabilizing at 3 weeks postoperatively.Ki67,PCNA,and N-cadherin were significantly expressed in the uterus and ectopic foci tissues,and their expression levels increased with modeling time,while E-cadherin expression in the uterus and ectopic foci tissues decreased with modeling time.These results showed good modeling success of the EMS rat model,suggesting that it could be used as a stable EMS modeling method.

Objective:To investigate the clinical characteristics and prognostic significance of germline mutations in patients with myelodysplastic neoplasms (MDS) .Methods:Clinical data from 407 patients with MDS [male, 252; female, 155; median age, 64 (range, 19-85) years] diagnosed at the First Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The clinical features and prognostic effects of germline mutations were evaluated.Results:The prevalence of germline mutations in patients with MDS was 5.9% (24/407), peaking at 20.0% in the group aged 21-30 years. The spectrum of germline mutations comprised DDX41 (9 cases, 2.2%), TP53 (3 cases, 0.7%), and single cases of RUNX1, TET2, MPL, CBL, ATRX, CEBPA, ETV6, IDH1, KDM5C, SBDS, GNAS, and CTC1. Patients with germline mutations exhibited significantly lower peripheral WBC counts than those without (1.87×10 9/L vs 2.50×10 9/L, P=0.018), but showed comparable median overall survival (21.3 months vs 21.1 months, P=0.97). Patients with DDX41 germline mutations, compared with those with other germline mutations, had a significantly older median age (65 vs 54 years, P=0.010), lower WBC counts (1.51×10 9/L vs 2.31×10 9/L, P=0.040), increased mean corpuscular volume (111.80 fl vs 97.25 fl, P=0.003), and a higher prevalence of normal karyotypes (100.0% vs 53.3%, P=0.022). The most frequently co-occurring somatic mutations in DDX41 germline mutation carriers were ASXL1, TET2, and RUNX1. Conclusion:In this study, the detection rate of germline mutations in MDS patients was 5.9% (24/407), peaking at 20% in the group aged 21-30 years. DDX41 and TP53 were the most prevalent germline mutations. DDX41 mutation carriers displayed distinct clinical characteristics; however, germline mutations overall showed no significant prognostic effect.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective A comparison of two method of establishing pressure ulcer rat models to determine which is the most suitable for experimental use.Methods 18 male SD rats were randomly divided into control(n=6),model A(n=6)and model B(n=6)groups.In the control group,iodophor treatment was given after hair removal at the simulated modeling site.In model group A,longitudinal compression was performed by simple deep-tissue foreign body implantation.In model group B,transverse compression was performed via the magnet compression method.The times required to complete the process and for each stage of pressure ulcer model establishment in each group were recorded.The general condition of the rats was observed,and the modeling rate,mortality rate,and infection rate were compared.Results By naked eye,we observed that the model A and model B groups gradually developed redness and swelling,ulceration,bleeding,exudation,and necrosis.Comparison of the whole time to produce pressure uler between model A and model B groups:the difference between the two groups was statitically significant(P＜0.05).Comparison of the time to produce pressure injury between Model A and Model B:The difference between the two groups at stage Ⅰ was not statistically significant(P＞0.05);the difference between the two groups at stage Ⅱ was statistically significant(P＜0 05);the difference between the two groups at stage Ⅲ was statistically significant(P＜0 05);the difference between the two groups at stage Ⅳ was statistically significant(P＜0 05).The mental and sports scores of the rats in the control group were significantly different from those in the model A and model B groups(P＜0.05).The general state of rats in the model group A was significantly different from that in the model B group,and coat color was dimer and activity decreased in the model group A.The modelling rate of rats in both model A and model B groups was 100％.The mortality and infection rates of the model group A were higher than those of the model group B,which were 33.34％and 16.70％,respectively.Conclusions Successful preparation of a four-stage model of pressure ulers in both modalities.The two method have both commonalities and distinct characteristics.The magnet compression method required less time,the rats were generally in good condition,and the mortality and infection rates were low;thus it is suitable for short-term intervention research.The simple deep-tissue foreign body implantation method took longer,required rats to have a certain level of tolerance,had high infection and mortality rates,and is more suitable for use for long-term observations of pressure ulcers.

Objective:To investigate the incidence characteristics and influencing factors of non-alcoholic fatty liver disease (NAFLD) in rural Uyghur ethnic group residents in Xinjiang Production and Construction Corps and to provide scientific evidence for early identification and prevention of NAFLD for residents.Methods:A total of 10 158 participants were included from the Xinjiang Uygur ethnic group population cohort. A prospective cohort study and Cox proportional hazards regression model analysis were used to explore the influencing factors and clustering of NAFLD, and the dose-response relationship between related biochemical indicators and the risk of NAFLD was studied using a restricted cubic spline.Results:The cumulative incidence rate of NAFLD was 6.9%, and the incidence density of NAFLD was 12.06/1 000 person-years. The incidence density of NAFLD in females was higher than in males (14.72/1 000 person-years vs. 9.17/1 000 person-years, P<0.001). The incidence density of NAFLD gradually increased with age in the total population, both men and women (all P<0.001). In the general population, an education level of junior high school or above was a protective factor for NAFLD, while older age, divorce, widowhood, overweight, obesity, hypertension, increased glomerular filtration rate, decreased HDL-C, increased LDL-C, and increased ALT were risk factors for NAFLD. Estimated glomerular filtration rate (eGFR), HDL-C, LDL-C, and ALT were non-linearly correlated with the incidence of NAFLD, and there was a significant dose-response relationship between them. Only 19.1% of residents had no NAFLD risk factors; over 80.9% had ≥1 NAFLD risk factors. The risk of NAFLD increased with the number of risk factors. Conclusions:The incidence of NAFLD in rural Uygur ethnic group residents in Xinjiang Production and Construction Corps was relatively low, but most residents had one or more risk factors for NAFLD. Prevention and control of NAFLD in this population cannot be ignored. In addition, people of older age, divorced or widowed, low education level, overweight or obese, hypertension, and abnormal eGFR, HDL-C, LDL-C, and ALT were the high-risk groups of NAFLD that need to be paid attention to in this population.

Objective To investigate the need for and utilization of health services among six Zhiguo ethnic minority groups in Yunnan Province,aiming to provide further evidence for the improvement of healthcare.Methods Using stratified random sampling,1921 individuals from six Zhiguo ethnic minority groups,aged 15 and above,were investigated with a structured questionnaire between August and December 2022.A structured questionnaire was used to collect participants'information on health service needs and utilization.Results Am-ong the surveyed participants,the two-week prevalence rate was found to be 22.54%,while the prevalence rate of chronic diseases was 38.52%.Among the residents,the risk of two-week prevalence was higher for females(OR=1.564),individuals aged≥60 years(OR=1.727),and those who reported poorer health utility value(OR=5.277),while it was lower for residents of Keno(OR=0.470)and Lahu(OR=0.659)ethnicity,as well as those who reported higher EQ-VAS scores(OR=0.446/0.174).Meanwhile,residents aged≥45 years(OR=3.392/7.072)were at higher risk for chronic disease prevalence,while it was lower for Keno ethnicity(OR=0.409),unmarried individuals(OR=0.479),and those with higher education levels(OR=0.629/0.603),higher EQ-VAS scores(OR=0.208)P<0.05.Additionally,among the participants,the treat-ment rate for two-week illness was 14.32%,while the non-treatment rate stood at 36.49%.Furthermore,the one-year hospitalization rate was reported as 19.89%,with a corresponding rate of individuals who needed hospitalization but did not receive it being recorded at 15.86%.Among the residents,the likelihood of treatment for two-week illness was higher for females(OR=1.461)and residents aged≥45 years(OR=1.510/1.560),whereas it was lower for individuals with higher EQ-VAS scores(OR=0.445).The likelihood of hospitalization within one year was also higher for residents aged≥60 years(OR=2.029)and individuals of Nu(OR=1.599),Lisu(OR=1.688),and Keno(OR=1.968)ethnicity,whereas those with high EQ-VAS scores(OR=0.325)had a lower risk(P<0.05).Conclusion In Yunnan Province,the need for healthcare services among six Zhiguo ethnic minority groups in this study is relatively low;however,the high prevalence of chronic diseases raises concerns.The utilization of healthcare services appears to be relatively sufficient,but the utilization of outpatient services still needs to be improved.

Objective:To analyze the mutation characteristics of rpoB gene in rifampicin-resistant Brucella strains. Methods:DNA of 4 rifampicin-resistant Brucella strains (JSY-26, G-9, WSY-13 and AW-3) isolated from Xinjiang Uygur Autonomous Region was selected, rifampicin rpoB gene was amplified by PCR and its nucleotide sequence was sequenced. The rpoB gene sequences of rifampicin-resistant Brucella standard strain (RB51) and sensitive strain (ALT-8) were used as reference, the mutation sites and types of the rpoB gene inside and outside the rifampicin resistance determination region (RRDR) of the 4 rifampicin-resistant Brucella strains were analyzed by Mega 7.0 software. Results:Through sequence alignment, both JSY-26 and WSY-13 strains underwent a single base point mutation at the RRDR 1 576 bp of the rpoB gene, with the base changing from guanine (G) to adenine (A). The G-9 strain underwent a single base point mutation at the RRDR 1 606 bp of the rpoB gene, with the base changing from cytosine (C) to A. The AW-3 strain showed 5 mutations of 3 types outside rpoB gene RRDR at 2 536, 2 537, 2 626, 2 636 and 2 654 bp, namely 3 insertion mutations [thymine (T) insertion once and C insertion twice], 1 deletion mutation (C deletion), and 1 single base point mutation (from G to C mutation).Conclusion:The RRDR mutations in the rpoB gene of the rifampicin-resistant Brucella strains are mainly characterized by single base point mutations, while multiple insertion and deletion mutations occur outside the RRDR.