Objective: To understand the epidemiological characteristics of pulmonary tuberculosis (PTB) in Shaanxi Province from 2016 to 2021, so as to provide the basis for improving PTB prevention and control strategies. Methods: The incidence data of PTB cases in Shaanxi Province were collected from the Tuberculosis Information Management System of the Chinese Disease Prevention and Control Information System from 2016 to 2021. The temporal, geographical, and demographic distribution characteristics of PTB were described. Results: A total of 121 280 PTB cases were reported in Shaanxi Province from 2016 to 2021, with the reported incidence rate decreasing from 56.30/105 in 2016 to 40.98/105 in 2021 (P<0.05). The etiological positivity rate increased from 16.61% in 2016 to 54.37% in 2021 (P<0.05). The average annual number of reported cases peaked in March (1 984.67 cases, accounting for 9.81%), followed by January (1 885.50 cases, accounting for 9.33%), and hit its lowest in October (1 458.50 cases, accounting for 7.22%). The incidence of PTB was relatively high in northern Shaanxi and southern Shaanxi, at 67.99/105 and 64.05/105, respectively, while it was relatively low in Guanzhong Region, at 44.83/105. The incidence rates of Ankang City (85.81/105), Fugu County (73.92/105), and Yulin City (72.20/105) ranked the top three. There were 80 111 male cases and 41 169 female cases of PTB, with a male-to-female ratio of 1.95︰1. The reported incidence rate of males (67.38/105) was significantly higher than that of females (36.61/105), and the difference was statistically significant (P<0.05). Among males, the highest average reported incidence rate was found in the 80 to <85 age group (179.46/105), while among females, the highest was in the 75 to <80 age group (104.38/105). The main occupations were farmers, accounting for 68.87% (83 526 cases). Conclusions The reported incidence rate of PTB in Shaanxi Province showed an overall downward trend from 2016 to 2021, with a high incidence in winter and spring. The epidemic in southern Shaanxi and northern Shaanxi is more severe than in Guanzhong Region of Shaanxi Province. The incidence of PTB is predominantly found among males, the elderly, and farmers.

Objective:To explore the expression levels and significance of programmed death factor 1 (PD-1)/programmed death factor ligand 1 (PDL-1) in T cells, regulatory T cells (Tregs), and regulatory B cells (Bregs) in patients with unexplained recurrent spontaneous abortion (URSA).Methods:Forty-two URSA patients (as patient group), 34 healthy pregnant women (as normal pregnancy group) and 30 unpregnant healthy examination patients (as control group) were collected for retrospective analysis,all study subjects were from patients who were treated in Taizhou Hospital affiliated to Wenzhou Medical University from February 2020 to February 2022. Flow cytometry was used to detect the expression level of PD-1/PDL-1 in Treg cells, Breg cells and [T cells, B cells and natural killer cells (TBNK)] lymphocyte subsets, as well as the expression level of serum Th1 (IFN-γ, TNF-α)/Th2 (IL-4, IL-6, IL-10)/Th17 (IL-17) cytokine expression. The patients were treated with lymphocyte immunotherapy, the changes of PD-1/PDL-1 levels were detected at the end of treatment, and the pregnancy outcome was recorded during follow-up. Comparisons between multiple groups were performed by ANOVA, comparisons before and after treatment in URSA patients were performed by paired T-test, and correlation of each test index by bivariate correlation analysis.Results:The expression levels of PD-1/PDL-1 in Treg, Breg cells and T lymphocyte subsets in peripheral blood of patients with URSA was significantly lower than that of healthy pregnant women(all P<0.01). The expression level of PD-1/PDL-1 in CD4+T cells was negatively correlated with the expression of serum Th1 cytokines Interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) (The r values were -0.44, -0.85, -0.33, and -0.94, respectively, all P<0.01). The expression level of PD-1/PDL-1 in CD4+T cells was positively correlated with the expression of serum Th2 cytokines interleukin 4(IL-4), interleukin 6(IL-6) and interleukin 10(IL-10)(The r values were 0.55, 0.47, 0.41, 0.33, 0.46, and 0.69, respectively,all P<0.01). The proportion of Breg cells and Treg cells were positively correlated with the level of serum IL-10 expression(The r values were 0.97, and 0.95 respectively, all P<0.01). The proportion of Treg cells was negatively correlated with the expression of IL-17( r=?0.95, P<0.01). The expression of PD-1/PDL-1 in Breg cells and Treg cells was positively correlated with the expression of serum IL-10(The r values were 0.95, 0.36, 0.96, and 0.95, respectively, all P<0.01). There was a negative correlation between serum IL-10 expression level and IL-17 expression level( r=?0.58, P<0.01). After URSA treatment, pregnancy was successful in 23 cases and failed in 19 cases. The expression of PD-1/PD-L1 on CD4, CD8, Tregs cells and Bregs cells in USRA treatment group was significantly higher than that before treatment( P<0.01), but there was no significant change in treatment failure group( P>0.05). Conclusion:The low expression of PD-1/PD-L1 in Treg cells, Breg cells and T cell subsets in peripheral blood of patients with URSA results in the immune imbalance of Th1/Th2 and Tregs/Th17, and the damage of maternal-fetal immune tolerance leads to pregnancy failure, which may be a potential therapeutic target.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Objective:This study aimed to investigate the clinical characteristics of patients diagnosed with primary hemophagocytic lymphohistiocytosis (pHLH) associated with perforin gene deficiency.Methods:We retrospectively analyzed the clinical data of 16 pHLH patients associated with perforin gene deficiency at Beijing Friendship Hospital, Capital Medical University, from April 2014 to August 2021. The mutation sites, mutation types, family history, clinical characteristics, and prognosis of the patients were assessed.Results:A total of 16 patients, including ten males and six females, with a median onset age of 17.5 years (range: 4-42 years), were enrolled in this study. Sixteen different mutations were identified, consisting of 11 missense mutations, one nonsense mutation, two frameshift mutations, and two in-frame mutations. All patients harbored at least one deleterious missense mutation, with the most common mutation sites being c.1349C>T (p.T450M) and c.503G>A (p.S168N). Decreased natural killer (NK) cell activity was observed in 11 patients, reduced perforin protein expression in ten patients, concurrent Epstein-Barr virus (EBV) infection at onset in eight patients, a family history in two patients, and central nervous system involvement in four patients. Eleven cases underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), with eight cases surviving. The median survival time of non-transplanted patients was eight months (range: 4-18 months), while that of transplanted patients was reported as "not reached".Conclusions:Emphasizing the diagnosis of pHLH in adults with perforin gene deficiency. In addition, it should be noted that EBV infection can potentially act as a triggering factor in such disease, and allo-HSCT exerts a substantial effect on the prognosis of patients.

Objective To investigate the risk factors of lymph node metastasis (LNM) in patients with superficial esophageal cancer (SEC) and to evaluate its clinical application.Methods From January 2010 to December 2016,769 SEC patients,who received surgery in the First Affiliated Hospital of Nanjing Medical University,were enrolled,and their clinical data were retrospectively analyzed.Chisquare test and logistic regression analysis were performed for statistical analysis.The sensitivity,specificity,and overall positive accuracy of pathological type and depth of invasion before operation were evaluated.Results The rate of LNM in patients with SEC was 15.34％ (118/769).There were significant differences in alcohol consumption,maximum tumor diameter,histological type,differentiation degree,depth of invasion and vascular invasion between patients with LNM (118 cases) and patients withoutLNM (651 cases) (x2=5.66,13.71,40.65,20.04,36.70 and 61.51;all P＜0.05).The results of multivariate analysis showed that maximum tumor diameter＞2 cm(odd ratio (OR) 1.76,95％ confidence interval (CI) 1.12 to 2.77),poor differentiation(OR 1.92,95％CI 1.23 to 3.01),submucosal invasion(OR 2.67,95％CI 1.28 to 5.56) and vascular invasion (OR 5.28,95％CI 2.75 to 10.13) were independent risk factors of LNM in patients with SEC.The tumor location was significantly correlated with the site of LNM (x2=107.05,P＜0.01).The sensitivity and specificity of preoperative assessment of LNM were 58 ％ (51/88) and 59 ％ (301/510),respectively.The overall positive accuracy of histological type before operation was 66.7％ (440/660).The overall positive accuracy of depth of invasion evaluated by endoscopic ultrasound before operation was 27.9％ (19/68).Conclusion Endoscopic treatment is recommended for SEC patients with maximum tumor diameter ≤ 2 cm,high ormoderate degree of differentiation,tumor confined to the mucosal layer and without vascular metastasis for the relatively low risk of LNM.

Objective To develop a nurse medication unsafe behavior scale, so as to provide an effective tool for evaluating nurses' unsafe behaviors and provide scientific basis for the safe medication management of clinical nurses. Methods From July to August 2016, a semi-structured interview was conducted among 5 nursing managers and 5 clinical nurses from an affiliated hospital of a medical university in Harbin city selected by purposive sampling method. The initial scale was formed by analyzing semi-structured interview data, combining with relevant literature. From November to December 2016, a pre-test was conducted among 380 nurses from an affiliated hospital of a medical university in Harbin city, who met the inclusion criteria, selected by convenience sampling method, by pre-test version of the scale. A large sample test scale was formed by expert review and pre-test. From January to February 2017, a total of 1 243 clinical nurses from 2 medical university affiliated hospitals, 2 provincial class Ⅲ grade A hospitals and 1 municipal class Ⅲ grade A hospital were selected by convenience sampling method for a large sample test, and the reliability and validity of the scale were tested to form the final scale. Results The nurse medication unsafe behavior scale consisted of 4 factors (treatment of medical orders, medication preservation and dispensing, medication administration and medication monitoring) and 25 items. The cumulative variance contribution rate was 60.897%. Confirmatory factor analysis showed that the fit indexes χ2/df, GFI, CFI, IFI and RMSEA were 2.872, 0.922, 0.951, 0.951 and 0.050 respectively. The content validity index was 0.96. The Cronbach's α coefficient and split half were 0.935 and 0.841 respectively. Conclusions The nurse medication unsafe behavior scale has good reliability and validity. It can be used as a valid tool to measure nurse medication unsafe behavior.

OBJECTIVE:To study the effects of salvianolic acid B(Sal B)on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac fibro-blast proliferation,secretion of type Ⅲ collagen,protein expressions of matrix metalloproteinase 9 (MMP-9),Smad2/3,Smad7, and explore its mechanism of anti-myocardial fibrosis. METHODS:Cells were divided into blank control group(culture medium) Ang Ⅱ model group,Sal B low-dose,medium-dose,high-dose groups (12.5,25,50 μmol/L). After cultured 1 h by blank or drug-containing culture,except for blank control group,cells in other groups were added 1 μmol/L Ang Ⅱ to induce proliferation. for 24 h. MTT method and hematoxylin-eosin staining method were adopted investigate the effect of Sal B on proliferation. Western blot method was adopted to detect the effects of Sal B on protein expressions of type Ⅲ collagen,MMP-9,Smad2/3,Smad7. RE-SULTS:Compared with blank control group,cells in Ang Ⅱ model group were significantly proliferated,protein expressions of type Ⅲ collagen,MMP-9,Smad2/3 were obviously enhanced,protein expression of Smad7 was obviously weakened,with statisti-cal significances(P<0.05). Compared with Ang Ⅱ model group,the cell proliferation in Sal B groups were inhibited,protein ex-pressions of typeⅢcollagen,MMP-9,Smad2/3 were weakened,while protein expression of Smad7 was enhanced. Except the pro-tein expression of type Ⅲ collagen in Sal B low-dose and medium-dose groups,the protein expression of Smad2/3 in Sal B high-dose group did not change significantly,other indexes had statistical significances(P<0.05). CONCLUSIONS:The anti-myo-cardial fibrosis effect of Sal B may be associated with inhibiting the proliferation of cardiac fibroblasts,down-regulating protein ex-pressions of typeⅢcollagen,MMP-9,Smad2/3 and up-regulating protein expression of Smad7.

Meditation error (ME) is a major contributor to patients' hospital injury. This paper,based on reviewing the influencing factors of ME at home and abroad,points out the risk factors that may lead to clinical nurses' ME and proposes corresponding measures with SHEL accident analysis to offer a basis for management of clinical nurses' meditation as well as secure and improve patients' meditation safety.

AIM:To investigate the effects of high plasma triglyceride (TG) caused by apolipoprotein C Ⅲ( ApoC Ⅲ) transgene on the occurrence and development of abdominal aortic aneurysm ( AAA) .METHODS:The animal models of hypercholesterolemia and hypercholesterolemia combined with hypertriglyceridemia were established by feeding high-fat diet to LDLR-/-and ApoC Ⅲ+LDLR-/-mice, respectively.AAA was induced in these mice by pancreatic elastase. By evaluating the incidence of AAA, relative maximal abdominal aortic diameter, disruption of the elastic lamellar structure and expression of matrix metalloproteinases ( MMPs) in the aorta walls of the AAA, the occurrence and development of AAA were compared in LDLR-/-and ApoC Ⅲ+LDLR-/-mice fed with either chow diet or high-fat diet.In addition, an in vitro TNF-α-induced aneurysmal microenvironment model on vascular smooth muscle cells ( VSMC) was used to study the impact of triglyceride-rich lipoproteins ( TRLs) from mice with normal or high contents of ApoCⅢon elastin protein expres-sion.RESULTS:Feeding the high-fat diet aggravated the severity of AAA in the LDLR-/-mice.ApoC Ⅲ+LDLR-/-mice fed with high-fat diet had less severe AAA than LDLR-/-mice fed with high-fat diet.TRLs inhibited degradation of VSMC elas-tin protein induced by TNF-α, and in vitro TRLs from the mice with high content of ApoC Ⅲ, compared to those with nor-mal content of ApoC Ⅲ, had better inhibitory effect on the degradation of elastin.CONCLUSION:High plasma TG caused by ApoC Ⅲtransgene alleviates AAA of the LDLR-/-mice induced by elastase and high-fat diet.The effect is probably attrib-uted to the hypertriglyceridemia caused by ApoC Ⅲtransgene.

Objective To study whether ultrasound combined with microbubbles induces suppress invasion in androgen-independent prostate cancer cells PC-3 and to identify the probable mechanism.Methods Ultrasound with a frequency of 21 kHz and intensity of 46 mW/cm2 in continuous wave mode was used.Ultrasound combined with microbubbles (200 μl SonoVue) was used to treat androgen-independent human prostate cancer PC-3 cells for 30 seconds.PC-3 cells were divided into three groups:control group,ultrasound group and ultrasound combined with microbubbles group.Twelve hours after treatment,cell growth curve we drawn,and transwell chamber model was used to do cell invasion experiments in vitro.Real-time PCR was used to measure the expression matrix metalloproteinase-2 and matrix metalloproteinase-9 messenger ribonucleic acid.Results Twelve hours after treatment,cell growth was not significant difference among three groups (P ＞ 0.05).Twelve hours after treatment,ultrasound combined with microbubbles could significantly inhibit the invasion of human prostate cancer cells (P ＜0.05).Treatment with ultrasound combined with microbubbles down-regulated the expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 messenger ribonucleic acid.Conclusions Ultrasound combined with microbubbles inhibited the invasion in human androgen-independent prostate cancer cells through down-regulation of matrix metalloproteinase-2 and matrix metalloproteinase-9.