OBJECTIVE To systematically evaluate the risk factors for ineffective eradication therapy of adult Helicobacter pylori （Hp） infection. METHODS Retrieved from PubMed，Web of Science， the Cochrane Library， Embase， CNKI， VIP and Wanfang Data， cohort studies and case-control studies on the eradication therapy for Hp infection in adult patients were searched from Jan. 2000 to Jul. 2024. After screening literature， extracting data， and evaluating the quality of literature， RevMan 5.3 software was used for meta-analysis， and sensitivity analysis and publication bias analysis were also performed. RESULTS A total of 19 articles were included， all of which were cohort studies， involving 9 931 patients in total. Among them， 1 929 patients were ineffective in eradication therapy， with the ineffective rates ranging from 8.02% to 33.33%. Meta-analysis showed that age＜50 years [OR＝1.33， 95%CI （1.12，1.57）， P＜0.001]， body mass index （BMI）＞25 kg/m2 [OR＝1.87， 95%CI （1.35， 2.59）， P＝ 0.000 2]， a history of smoking [OR＝1.62， 95%CI（1.35， 1.95）， P＜0.001]， a history of drinking [OR＝1.93， 95%CI（1.47， 2.54）， P＜0.001]， living in a rural area [OR＝1.74， 95%CI（1.41， 2.15）， P＜0.001]， having non-peptic ulcer [OR＝3.45， 95%CI （1.75， 6.67）， P＝0.000 3]， a family members’ infection history [OR＝4.72， 95%CI（3.32， 6.74）， P＜0.001]， poor treatment compliance [OR＝4.89， 95%CI （3.07， 7.79）， P＜0.001]， amoxicillin resistance [OR＝3.42， 95%CI （1.95， 6.00）， P＜0.001] and clarithromycin resistance [OR＝8.14， 95%CI（5.00， 13.24）， P＜0.001] had significant impacts on ineffective eradication therapy of Hp infection in adults. Sensitivity analysis and publication bias analysis showed that the result of this study was robust and reliable. CONCLUSIONS Age＜50 years， BMI＞25 kg/m， a history of smoking， a history of drinking， living in a rural area， having non-peptic ulcer， a family members’ infection history， poor treatment compliance， amoxicillin resistance and clarithromycin resistance are risk factors for failure of Hp infection eradication therapy in adults.

ObjectiveTo investigate the effect and mechanism of Polygonatum neutral polysaccharides from sibiricum （PSP-NP） on colon injury in mice with chronic obstructive pulmonary disease （COPD）. MethodsMale C57BL/6J mice were randomly divided into a control group， a COPD model group， and a PSP-NP group. The COPD model was established using smoke exposure combined with intranasal LPS administration. The PSP-NP group was simultaneously treated daily with 200 mg/kg of PSP-NP via intragastric gavage， while the other groups received an equal volume of saline. HE staining was used to observe the pathological changes in the colon. ELISA was employed to detect the levels of LPS in serum and the expressions of ZO-1， Occludin， IL-6， and TNF-α in colon tissue. UPLC-MS was used to detect the types and contents of bile acids in colonic content， and to screen for differential bile acids. Differential microbial flora were identified using 16S rRNA gene sequencing， and correlation analysis was conducted with differential bile acids. PSP-NP was combined with the differential bile acids cholic acid （CA）， and deoxycholic acid （DCA） in vitro to analyze the binding capacity of PSP-NP for CA and DCA. PSP-NP was applied to NCM460 normal colonic epithelial cells cultured in CA and DCA. Cell migration ability was assessed using the scratch assay， and the mRNA expression levels of inflammatory cytokines TNF-α， IL-6， and NF-κB were measured by RT-qPCR. ResultsPSP-NP effectively improved colonic damage in COPD model mice， enhanced mechanical barrier function， alleviated inflammatory response， and regulated abnormal changes in colonic flora and bile acid metabolism. Correlation analysis further revealed that PSP-NP regulated colonic bile acid metabolism and reduced the redundancy of secondary bile acids by increasing the relative abundance of Bacteroidota， Verrucomicrobiota， Bacteroides， and Akkermansia， while decreasing the relative abundance of Lactobacillus and Bifidobacterium. Notably， in vitro binding assays demonstrated that PSP-NP bound to differential bile acids DCA and CA， with the strongest binding capacity for DCA at 58.2%. In cellular functional studies， DCA inhibited the migration ability of colonic epithelial cells NCM460 and significantly increased the relative mRNA expression levels of inflammatory factors TNF-α， IL-6， and NF-κB. Importantly， co-treatment with PSP-NP significantly ameliorated the impact of DCA on NCM460 cells. ConclusionsPSP-NP may significantly improve colonic damage in COPD model mice. The mechanism may involve the regulation of colonic bile acid metabolism and bile acid profiles through both microbial modulation and direct binding， thereby reducing the damage caused by secondary bile acids such as DCA to colonic epithelial cells.

OBJECTIVES: To explore the value of serum cystatin C (CysC) levels in evaluating renal prognosis in IgA nephropathy (IgAN) patients. METHODS: We retrospectively collected the clinical data of IgAN patients diagnosed by renal biopsy at Guangdong Provincial People's Hospital from January, 2014 to December, 2018. Based on baseline serum CysC levels, the patients were divided into high serum CysC (>1.03 mg/L) group and normal serum CysC (≤1.03 mg/L) group. The composite endpoint for poor renal prognosis was defined as ≥50% decline in estimated glomerular filtration rate (eGFR) and/or progression to end-stage renal disease (ESRD). Lasso regression, multivariate Cox regression and Kaplan-Meier survival analysis were used to identify the risk factors and compare renal survival rates between the two groups. Smooth curves fitting and threshold effect analysis were used to explore the relationship between serum CysC levels and the outcomes. A nomogram model was constructed and its predictive performance was evaluated using concordance index, calibration curve, receiver operating characteristic (ROC) curve and the area under curve (AUC). RESULTS: A total of 356 IgAN patients were enrolled, who were followed up for 4.65±0.93 years. The composite endpoint occurred in 74 patients. High serum CysC was identified as an independent risk factor for poor renal prognosis in IgAN (HR=2.142, 95% CI 1.222 to 3.755), and the patients with high serum CysC levels had a lower renal survival rate (Log-rank χ²=47.970, P<0.001). In patients with serum CysC below 2.12 mg/L, a higher CysC level was associated with an increased risk of poor renal prognosis (β=3.487, 95% CI: 2.561-4.413, P<0.001), while above this level, the increase of the risk was not significant (β=0.676, 95% CI: -0.642-1.995, P=0.315). The nomogram model based on serum CysC and 3 other independent risk factors demonstrated good internal validity with a concordance index of 0.873 (95% CI: 0.839-0.907) and an AUC of 0.909 (95% CI: 0.873-0.945). CONCLUSIONS Serum CysC levels are associated with renal prognosis in IgAN patients, and high serum CysC an independent risk factor for poor renal prognosis.
Humans ; Glomerulonephritis, IGA/diagnosis* ; Cystatin C/blood* ; Prognosis ; Risk Factors ; Retrospective Studies ; Glomerular Filtration Rate ; Kidney Failure, Chronic ; Male ; Female ; Adult ; Nomograms ; Middle Aged

Autoimmune hepatitis （AIH） is an autoimmune disease characterized by chronic liver inflammation， with a gradually increasing incidence rate， and its social and medical burdens cannot be neglected. Intestinal microecology is becoming a research hotspot in the field of autoimmune disease. In recent years， it has been believed that changes in intestinal microecology can cause changes in autoimmune state， microbial metabolites， and intestinal barrier， which is one of the driving factors for the onset of AIH. Early diagnosis and correct treatment can help to improve the prognosis of AIH patients. This article introduces the characteristics of gut microbiota in AIH patients， elaborates on the impact of intestinal microflora imbalance on the pathogenesis of AIH， and briefly describes related treatment regimens from the perspective of intestinal microecology， so as to comprehensively understand and explain the role of intestinal microecology in AIH and the impact of intestinal microecology balance on the pathogenesis， diagnosis， and treatment of AIH.

AIM: To investigate the diagnostic value of the axial length/corneal radius of curvature(AL/CR)for myopia in children and adolescents.METHODS: PubMed, Embase, The Cochrane Library, CNKI, CBM, WanFang Data and VIP databases were searched to collect clinical research on the value of AL/CR in diagnosing myopia in children and adolescents, and the retrieval time was from establishment to September 30, 2023. The QUADAS-2 tool was used to evaluate the quality of the extracted literature. A random-effects model was used to pool diagnostic test data, Meta-regression and subgroup analysis were performed to explore sources of heterogeneity.RESULTS: A total of 10 articles involving 19 872 study participants were included, and Meta-analysis showed that the pooled sensitivity of the AL/CR for the diagnosis of myopia in children and adolescents was 0.91[95%CI(0.90-0.91)], the pooled specificity was 0.84 [95%CI(0.84-0.85)], and area under the SROC curve of 0.95 [95%CI(0.93-0.96)].CONCLUSION: The AL/CR is a good indicator of myopia in children and adolescents.

Objective To investigate the effect of the protein kinase RNA-like endoplasmic reticulum kinase(PERK)/eukaryotic initiation factor 2α(eIF2α)pathway in endoplasmic reticulum stress on the activation of hepatic stellate cells(HSC).Methods Pathological sections of normal liver tissue after surgery were collected from 11 patients with hepatic fibrosis(S1-S4)and 9 patients with hepatic hemangioma and hepatic adenoma confirmed by liver biopsy,and immunohistochemistry was used to measure the protein expression levels of PERK,eIF2α,and C/EBP homologous protein(CHOP).Human HSC-LX2 cells were treated with different concentrations of the endoplasmic reticulum stress inducer thapsigargin(0,125,250,500,and 1 000 nmol/L),and qRT-PCR was used to measure the mRNA expression level of PERK,while Western blot was used to measure the protein expression levels of PERK,inositol requiring protein 1(IRE1),activating transcription factor 6(ATF6),CHOP,and α-smooth muscle actin(α-SMA).The method of lentivirus transfection was used to construct a PERK stable overexpression LX-2 group and a control group;qRT-PCR was used to measure the mRNA expression levels of PERK,eIF2α,and α-SMA,Western blot was used to measure the protein expression levels of PERK,phosphorylated eIF2α(p-eIF2α),and α-SMA,and immunofluorescence assay was used to measure the expression of collagen type Ⅰ alpha 1(COL1A1).The independent samples t-test was used for comparison of normally distributed continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.Results Compared with normal liver tissue,the liver tissue of patients with hepatic fibrosis had significantly higher expression levels of PERK,eIF2α,and CHOP(Z=-3.56,t=-5.75,Z=-3.52,all P<0.001).Compared with the solvent group,the groups treated with different concentrations of thapsigargin had significant increases in the expression levels of the endoplasmic reticulum-associated proteins PERK,CHOP,IRE1,ATF6,and α-SMA(all P<0.05).Compared with the control group,the PERK stable overexpression group had significant increases in the mRNA expression levels of PERK,eIF2α,and α-SMA and the protein expression levels of PERK,p-eIF2α,and α-SMA(all P<0.05),and immunofluorescence assay showed a significant increase in the expression level of COL1A1 in the PERK stable overexpression group(P<0.05).Conclusion PERK overexpression can induce the expression of α-SMA and COL1A1 in LX-2 cells,suggesting that the PERK signaling pathway might be one of the important mechanisms of HSC activation.

The theory of “rhythmic equilibrium” is developed based on the idea of sharing the same laws between nature and human， and by integrating with the medical concept of homeostasis of calm yin and sound yang. "Rhythmic instability" runs through the entire process of the occurrence and development of myopia， covering four aspects including imbalance of rhythm （high-risk period of myopia）， imbalance of qi and blood （premyopia）， imbalance of sinew-membranes （low myopia）， and imbalance of essence and blood （high myopia）. The treatment should focus on adjusting the rhythm and harmonizing situation， which can help balance yin and yang， and nourish the eye system. For high-risk period of myopia， adjusting sleeping time and increasing outdoor activities are stressed to adjust the rhythm in a timely manner. In the stage of premyopia， appropriate techniques of traditional Chinese medicine （TCM） such as pressing needles can be added to harmonize qi and blood. In the period of low myopia， appropriate TCM techniques such as pressing needles and ear acupuncture are mainly used， supplemented by modified Danggui Buxue Decoction （当归补血汤） to soften tendons and unblock collaterals. During the period of high myopia， it is recommended to control the development of existing disease and put focus on nourishing essence and blood， usually with Zhujing Pill （驻景丸） or modified Siwu Wuzi Decoction （四物五子汤） to restore the stability of the eyes and the whole body.

As a new hypoglycemic drug,Dapagliflozin has attracted much attention because of its unique hypoglycemic mechanism. It has been used in many studies on type 2 diabetes mellitus,but the application of type 1 diabetes mellitus(T1DM)in the eastern population is rare. This article uses Dapagliflozin through a case of obese T1DM to provide new ideas for the treatment of T1DM.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Background and objective Small cell lung cancer(SCLC)is known as recalcitrant cancer with high malignancy and heterogeneity.Immunotherapy has changed the treatment pattern of extensive-disease SCLC(ED-SCLC),but the beneficiary population is limited.Therefore,exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC.SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase Ml(PKM1)is one of the isozymes of PK,an important rate-limiting enzyme in glycolysis pathway.Previous studies have shown that PKM1 is related to autophagy and drug sensitivity,however,how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear.The aim of this study was to investigate the biological functions of PKM1 in SCLC,including its effects on proliferation,migra-tion,autophagy,drug sensitivity,and expression of neuroendocrine(NE)-related markers in SCLC.Methods Western blot was used to detect the expression level of PKM1 in SCLC cells.PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection.Proliferation of cells and drug sensitivity were detected by MTT,and migration ability of cells was determined by Transwell.The level of autophagy was detected by flow cytometry.Western blot was used to determine the expression levels of NE-related proteins.Results PKM1 was differentially expressed among various SCLC cell lines,and was lower in H1092 cells(P＜0.01).Compared with the control group,there was no significant difference in proliferation level of PKM1 overexpressing H1092 cell,but the migration ability was significantly increased(P＜0.001),the drug sensitivity was re-duced,and the level of autophagy was inhibited(P＜0.001).Additionally,overexpression of PKM1 could upregulate the expres-sion of non-neuroendocrine(non-NE)-related proteins(P＜0.01)and decrease the expression of NE-related proteins(P＜0.01).Conclusion PKM1 was differentially expressed in SCLC cell lines,and high expression of PKM1 did not affect the prolifera-tion,but affected the migration of SCLC cells.PKM1 might affect drug sensitivity by inhibiting autophagy and regulating the expression of NE markers.These results provide a theoretical basis for exploring the role of PKM1 in SCLC.