ObjectiveTo investigate the effects of probiotics combined with bismuth quadruple therapy （BQT） on clinical efficacy、gastrointestinal adverse reactions and intestinal flora in Helicobacter pylori （HP） positive patients. MethodsThe patients who were positive for HP from May 2023 to July 2023 in the department of gastroenterology of Shanghai first people's hospital were randomly divided into2 groups with 40 people in each group. The probiotic group was given 2 weeks of quadruple therapy with probiotics and standard BQT， followed by 4 weeks of oral probiotics after quadruple discontinuation. The placebo group was given 2 weeks of probiotic placebo and standard BQT， followed by 4 weeks of oral probiotic placebo. ¹³C urea breath test was used to evaluate the clinical efficacy， gastrointestinal symptoms rating Scale was used to evaluate the gastrointestinal adverse reactions of patients before and after the intervention， and microbial diversity 16S rDNA sequencing technology was used to detect the level of intestinal flora of patients before and after the intervention. ResultsThere was no significant difference in the eradication rate between the two groups （P>0.05）. Before the intervention， there was no significant difference in the scores of the gastrointestinal symptom rating scale between the probiotic group and the placebo group. After the intervention， patients in the probiotic group had significantly lower pain scores on acid reflux （1.10±0.30 vs 1.35±0.53， P<0.05） and stomach or abdominal hunger than in the placebo group （1.07±0.26 vs 1.30±0.52， P<0.05）. Through the before-and-after comparison of the probiotic group， the scores of abdominal pain （1.24±0.44 vs 1.58±0.71， P<0.05）， stomach or abdominal hunger （1.07±0.26 vs 1.27±0.45， P<0.05） and dry and hard stool （1.24±0.49 vs 1.48±0.75，P<0.05） were significantly lower in the probiotic group than before the intervention in the probiotic group. ConclusionProbiotics combined with BQT can improve the gastrointestinal adverse reactions and intestinal flora disorders in the process of quadruple drug therapy， but it does not improve the eradication rate of HP.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

[摘 要] 目的：探讨1,25-二羟维生素D3 [1,25(OH)2D3]对食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）细胞增殖、迁移和细胞周期的影响及其相关机制。方法：用不同浓度1,25(OH)2D3处理ESCC细胞TE-11、KYSE30、TE-1和KYSE510后，用CCK-8法检测细胞的增殖能力。再用浓度分别是0、0.1、0.15、0.2 μmol/L的1,25(OH)2D3处理TE-11和KYSE30细胞，划痕愈合实验、流式细胞术分别检测细胞的迁移能力和细胞周期分布情况，WB法检测细胞中cyclin D1、P27、ERK和p-ERK蛋白的表达水平。结果：1,25(OH)2D3显著抑制TE-11和KYSE30细胞的增殖能力，其抑制程度呈时间依赖性和浓度依赖性。0.1和0.2 μmol/L的1,25(OH)2D3处理48 h后，与空白对照组比较，TE-11和KYSE30细胞的迁移能力均显著降低（P<0.05或P<0.01），处于G0/G1期细胞显著增加（P<0.05或P<0.01），细胞中cyclin D1和p-ERK蛋白水平显著下调、P27蛋白水平明显上调（P<0.05或P<0.01）而ERK蛋白的表达无明显变化。结论：1,25(OH)2D3显著抑制ESCC细胞的增殖和迁移能力并阻滞细胞周期进程，其可能通过调控ERK信号通路而发挥作用。

Objective To investigate the correlations of plasma homocysteine(Hcy)levels with cerebral white matter lesion(WML)severity and cognitive impairment in elderly hypertension patients.Methods A retrospective case-control study was conducted.Ninty-eight elderly patients with hypertension were enrolled.Based on the presence or absence of hyperhomocysteinemia(hypertension with plasma Hcy levels ≥10μmol/L was defined as H-type hypertension),patients were divided into two groups:a control group(n =48) and an H-type hypertension group(n =50).The degree of WML was rated by the Fazekas scale using magnetic resonance imaging(MRI)analysis.Neuropsychological examinations including mini-mental state examination(MMSE)and Montreal cognitive assessment (MoCA)were taken to assess cognitive function.The degree of WML and cognitive impairment were compared between the two groups.Correlations of plasma Hcy levels with the degree of WML and cognitive impairment were analyzed.Results Compared with the control group,scores of the Fazekas scale(3.2 ± 1.0 vs.2.5 ± 1.0,P ＜0.05) and deep white matter hyperintensity on MRI(1.7 ± 0.8 vs.1.3±0.7,P＜0.05)increased,and scores of MMSE(24.9±3.3 vs.27.7±1.8,P＜0.05)and MoCA(18.6±3.9 vs.25.0±3.0,P＜0.05)decreased in the H-type hypertension group.Plasma Hcy levels were positively correlated with the degree of WML (r =0.430,P ＜ 0.01) and negatively correlated with cognitive function(r=-0.406 in MMSE and-0.663 in MoCA,P＜0.01).Multivariate logistic regression showed that Hcy,fasting blood-glucose,deep WML,low-density lipoprotein cholesterolin,age and systolic pressure were influencing factors for cognitive impairment (P ＜ 0.01).Conclusions WML and cognitive function are worse in elderly H-type hypertension patients than in hypertension patients with normal Hcy levels.WML and cognitive impairment are aggravated with increased plasma Hcy levels.The plasma Hcy level may be an effective clinical indicator of cognitive function in elderly people with hypertension.

The content of endogenous anabolic steroids is extremely low in biological matrices.Its chemical structure contains polar functional groups such as hydroxyl and carbonyl, which limits their applicability in GC-MS.The lack of ionized groups in the chemical structure leads to poor sensitivity in LC-MS, which plays a significant role in various physiological activities analysis.It is an effective way to enhance the response of mass spectrometer by modifying the chemical structure of endogenous anabolic steroids through derivatization technology.This review summarizes various derivatization reagents and corresponding derivatization processes of endogenous anabolic steroids analysis in the methods based on different testing instruments and methodologies.The advantage and disadvantage of all kinds of derivatiaztion methods and the prospect of the endogenous anabolic steroids derivatiaztion techniques are also discussed.

Objective: To investigate the detection rates and inlfuencing factors of atrial septal defect (ASD) and ventricular septal defect (VSD) among neonates in two cities of East China and to provide scientiifc basis for the prevention, diagnosis, treatment and monitor of ASD and VSD. Methods: 2100 newborns with gestational age of at least 28 weeks were recruited consecutively from each city between 2013-09 and 2014-11. Data related to ASD and VSD were collected by questionnaires and echocardiographic screening was conducted within 7 days after birth. Results: A total of 4152 neonateswere examined with gestational age of (39.03 ± 1.29) weeks, among whom 2189 were male infants (52.72%), and age of mother was (26.32 ± 4.10) years old. Detection rates of ASD and VSD were 60.5‰ and 12.8‰ respectively, showing no significant difference between genders (P>0.05). Multivariate logistic regression analysis showed that maternal pre-pregnancy BMI and home decoration were the inlfuencing factors of ASD and maternal drug use in early pregnancy was the inlfuencing factor of VSD among newborns. Conclusions: Detection rates of ASD and VSD among neonates were relatively high in two cities of East China. Early screening is importtant to reduce the incidence of ASD and VSD and improve the prognosis.

Treatment with the combination of Chinese herbs and cytotoxic chemotherapies showed a higher survival rate in clinical trials. In this report, the results demonstrated that the tanshinone II A, a key component of Salvia miltiorrhiza bunge, when it is combined with the cytotoxic drug cisplatin showed synergistic antitumor effects on human prostate cancer PC3 cells and LNCaP cells in vitro. Antiproliferative effects were detected with MTT assay. Cell cycle distribution and apoptosis were detected by flow cytometer. Protein expression was detected by Western blotting. The intracellular concentration of cisplatin was detected by high performance liquid chromatography. The results demonstrated that tanshinone II A significantly enhanced the antiproliferative effects of cisplatin on human prostate cancer PC3 cells and LNCaP cells with the increase of the intracellular concentration of cisplatin. These effects were correlated with cell cycle arrested at S phase and cell apoptosis. The apoptosis might be achieved through death receptor pathway and mitochondrial pathway. Furthermore, the Bcl-2 family members were also involved in this apoptotic process. Collectively, these results indicated that the combination of tanshinone II A and cisplatin had a better treatment effect in vitro not only on androgen-dependent LNCaP cells but also on androgen-independent PC3 cells.

This study is to investigate the antitumor activity of ophiopogonin B (OP-B). MTT assay, flow cytometric analysis, acridine orange staining, Lyso-Tracker Red staining and HeLa-GFP-LC3 transfect cells assay were used to detect the proliferation activity, apoptosis and autophagy of HeLa cells. The results showed that OP-B exerted potent antiproliferative activity on HeLa cells, the cell growth inhibition effect of OP-B was not due to apoptosis and OP-B could induce autophagy of HeLa cells. OP-B also induced the protein expression up-regulation of Beclin-1 and promoted LC3 I transformation LC3 II, which were representative proteins of autophagy. Furthermore, 3-MA, an inhibitor of autophagy, not only inhibited OP-B-mediated autophagy but also almost completely reversed the antiproliferative effect of OP-B, suggesting that the growth inhibition effect of OP-B was autophagy dependent. Western blotting demonstrated that OP-B inhibited the phosphorylation of Akt and its' downstream vital protein, such as mTOR and p70S6K. In addition, OP-B also induced the protein expression up-regulation of PTEN, which is a negative regulation protein for Akt/mTOR signaling pathway. However, OP-B did not affect the protein expression of total Akt. Collectively, the antitumor effects of OP-B were autophagy-dependent via repression Akt/mTOR signaling pathway. Therefore, OP-B is a prospective inhibitor of Akt/mTOR and may be used as an alternative compound to treat cervical carcinoma.

Objective To explore the roles of follicular helper T cells (Tfh) in the pathogenesis of pemphigus and bullous pemphigoid (BP).Methods Venous blood was collected from 20 patients (including 10 cases of pemphigus and 10 cases of BP) and 20 age- and sex-matched normal human controls.Enzyme linked immunosorbent assay (ELISA) was performed to measure the levels of serum interleukin (IL)-21 and anti-BP180-NC16A antibody,and flow cytometry to detect the percentage of Tfh in peripheral blood mononuclear cells (PBMCs).The relationship of anti-BP180-NC16A antibody titer to Tfh and IL-21 levels was assessed by linear correlation analysis.Results The serum IL-21 level and Tfh percentage in PBMCs were significantly higher in patients with pemphigus than in the normal controls (95.33 ± 33.69 vs.54.50 ± 18.13 pg/ml,t =3.38,P＜ 0.01;12.08％ ± 4.74％ vs.6.15％ ± 1.62％,t =3.74,P ＜ 0.01),and higher in patients with BP than in the normal controls ( 106.70 ± 44.91 vs.55.37 ± 15.89 pg/ml,t =3.41,P ＜ 0.01; 11.85％ ± 3.14％ vs.6.03％ ± 1.74％,t =5.13,P ＜ 0.01 ).The titer of anti-BP180-NC 16A antibody was positively correlated with the percentage of Tfh (r =0.67,P＜ 0.05) and serum level of IL-21 (r=0.77,P＜ 0.01) in patients with BP.Conclusions There is a significant increase in the percentage of Tfh and serum level of IL-21 in patients with pemphigus and BP,hinting a certain role of Tfh and IL-21 in the pathogenesis of pemphigus and BP.

Objective To develop a special stool collector for paraplegic patients with constipation,and to observe the clinical effects. Methods 52 paraplegic patients with constipation were divided into group A(30 cases) and group B(22 cases ).Group A used type one stool collector and goup B chose type two stool collector. The time of dealing with defecation, exposure time, pollution area, the usage of urinal pad, toilet paper, clean water before and after the special toilets were observed between the two groups. Results Each indicator significantly changed after using two types of stool collectors in the two groups of patients and above were significantly decreased. Conclusions The special stool collector for the paraplegic patients with constipation can effectively avoid the soakage of the anal and buttocks skin, reduce the environment pollution of the odor, reduce labor intensity and lower care costs.