AIM: To explore the efficacy of 0.05% cyclosporine A combined with olopatadine eye drops in treating allergic conjunctivitis-related dry eye disease.METHODS: A total of 63 patients(63 eyes)with allergic conjunctivitis-related dry eye disease in the People's Hospital of Guangxi Zhuang Autonomous Region from August 2022 to April 2023 were enrolled and randomly divided into control group(n=33)and observation group(n=30). The patients of the control group were administrated with 0.1% olopatadine eye drops and 0.3% sodium hyaluronate eye drops, while the observation group was administrated with 0.1% olopatadine eye drops and 0.05% cyclosporine A eye drops. The ocular surface disease index(OSDI), total ocular symptom score(TOSS), conjunctival congestion score, conjunctival papillae and follicle score, Schirmer I test(SⅠt), tear meniscus height(TMH), meibomian gland secretion ability and property score, meibomian gland loss area score, corneal fluorescein staining(CFS), tear film break-up time(BUT), noninvasive first tear film break-up time(NIBUTf), noninvasive average tear film break-up time(NIBUTav)before and after treatment and the drug safety during the treatment period of both groups of patients were evaluated.RESULTS: After treatment, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, SⅠt, TMH, meibomian gland secretion ability score and property score, CFS, BUT, NIBUTf, and NIBUTav of the observation group showed improvements compared with those before treatment(all P<0.017). Among these, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, BUT, NIBUTf, and NIBUTav demonstrated significant improvement compared with the control group(all P<0.05). There was no statistically significant difference in meibomian gland loss area score between the two groups before and after treatment(P>0.05). During the treatment period, there were no local or systemic adverse reactions.CONCLUSION: The combined use of 0.05% cyclosporine A and olopatadine eye drops can significantly improve ocular discomfort symptoms of patients with dry eye disease associated with allergic conjunctivitis, such as red eyes, itchy eyes and foreign body sensation, promote tear film stability and have high safety.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Lung cancer exhibits the highest incidence and mortality rates among cancers globally, with a five-year overall survival rate alarmingly below 20%. Targeting autophagy, though a controversial therapeutic strategy, is extensively employed in clinical practice. Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy. Nevertheless, the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention. This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer. It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells. Notably, most autophagy-targeting drugs, primarily natural small molecules, have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer, as opposed to inhibiting protective autophagy. These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies, offering promising approaches to combat this disease.

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applica-tions of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

Objective To investigate the relationship between serum levels of vitamin D(VD)and brain derived neurotrophic factor(BDNF)and restless leg syndrome(RLS)in maintenance hemodialysis patients.Methods A total of 168 end-stage renal disease patients admitted to the hospital for maintenance hemodialy-sis treatment from May 2021 to May 2022 were regarded as the observation group.According to whether they had concurrent RLS,they were separated into concurrent RLS group and non concurrent RLS group.In addi-tion,121 healthy volunteers who came to the hospital for physical examination were regarded as the control group.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of VD and BDNF in ser-um,multivariate Logistic regression was applied to analyze the influencing factors of RLS in maintenance he-modialysis patients.Receiver operating characteristic(ROC)curve was plotted to analyze the predictive value of single and combined detections of VD and BDNF for RLS in maintenance hemodialysis patients.Results Compared with the control group,the serum levels of VD and BDNF in the observation group were reduced(P<0.05).Compared with the non concurrent RLS group,the continuous dialysis time and serum ferritin level in the non concurrent RLS group were increased,while serum VD and BDNF levels were reduced(P<0.05).Multivariate Logistic regression analysis showed that VD and BDNF were protective factors for RLS in maintenance hemodialysis patients,while continuous dialysis time and ferritin were risk factors for RLS in maintenance hemodialysis pa-tients(P<0.05).The area under the curve of the combined prediction of VD and BDNF for RLS in mainte-nance hemodialysis patients was 0.889,which was superior to those of single detection(Zcombination-VD=3.748,Zcombination-BDNF=2.245,P<0.05),and the sensitivity of the combined detection was 86.11%,and the specificity was 79.55%.Conclusion The levels of VD and BDNF in serum are protective factors for RLS in maintenance hemodialysis patients.The combination of the two could effectively predict RLS in maintenance hemodialysis patients.

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT₇ receptor protein expression in the cells, indicating potential antidepressant activity.

Objective To investigate the causes of a cluster of suspected neonatal carbapenem-resistant Klebsiella pneumoniae(CRKP)bloodstream infection(BSI)in the neonatal department of a hospital,and provide references for the effective control of the occurrence of healthcare-associated infection(HAI).Methods Epidemiological in-vestigation on 3 neonates with CRKP BSI in the neonatal department from January 31 to February 6,2023 was per-formed.Specimens from environmental object surfaces were taken for environmental hygiene monitoring,and effec-tive control measures were taken according to the risk factors.Results From January 31 to February 6,2023,a to-tal of 60 neonates were admitted in the neonatal department,including 16 with peripherally inserted central venous catheter(PICC).Three neonates had CRKP BSI,with a incidence of 5.00％.There were 33 hospitalized neonates on the day(February 7)when the cluster of HAI was reported,with a prevalence rate of 9.09％(3/33).CRKP BSI rate in the neonatal department of this hospital from January 31 to February 6,2023 was higher than that in 2022(P＜0.001).The incubators of the 3 neonates with CRKP BSI were in the same ward and adjacent to each other.The first neonate with CRKP BSI(who developed BSI on January 31)underwent PICC maintenance on Feb-ruary 4,and the other 2 neonates with PICC maintenance immediately following the first one also developed CRKP BSI.CRKP were isolated from blood culture of all 3 neonates,and antimicrobial susceptibility testing results were consistent.Conclusion The occurrence of the cluster event of neonatal CRKP BSI may be related to the failure of strict implementation of aseptic procedures during PICC maintenance and cross contamination among items.

Objective:To study the clinical effect of combined capsules of live Bifidobacterium, Lactobacillus and Enterococcus assisted triple therapy in chronic gastritis children with Helicobacter pylori ( Hp) positive. Methods:The clinical data of 80 chronic gastritis children with Hp positive from January 2019 to March 2022 in Wuxi Children′s Hospital were retrospectively analyzed. Among them, 40 children (combination group) were treated with combined capsules of live Bifidobacterium, Lactobacillus and Enterococcus combined with triple therapy (omeprazole, amoxicillin and clarithromycin), 40 children (control group) were treated with triple therapy, and all children were treated for 4 weeks. The efficacy, Hp clearance rate (performed 13C breath test after 4 weeks of discontinuation) and symptom improvement (the scores of upper abdomen pain, anorexia and sour regurgitation) were compared between two groups. The feces before treatment and after treatment were collected, and the intestinal flora was detected, including Bifidobacterium, Lactobacillus, Bifidobacterium/ Enterobacteria; the levels of C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10) and nuclear transcription factor κB (NF-κB) before treatment and 14 d after treatment were detected; the adverse reactions (vomiting, diarrhea, dizziness and erythra) were detected. Results:The total effective rate and Hp clearance rate in combination group were significantly higher than those in control group: 95.00% (38/40) vs. 80.00% (32/40) and 92.50% (37/40) vs. 75.00% (30/40), and there were statistical differences ( P<0.05). The scores of upper abdomen pain, anorexia and sour regurgitation after treatment in combination group were significantly lower than those in control group: (0.56 ± 0.14) scores vs. (1.12 ± 0.35) scores, (1.20 ± 0.37) scores vs. (1.50 ± 0.42) scores and (1.02 ± 0.28) scores vs. (1.39 ± 0.43) scores, and there were statistical differences ( P<0.01). The Bifidobacterium, Lactobacillus, Bifidobacterium/ Enterobacteria after treatment in combination group were significantly higher than those in control group: (8.56 ± 1.35) lgcfu/g vs. (7.94 ± 1.32) lgcfu/g, (9.27 ± 1.63) lgcfu/g vs. (8.35 ± 1.58) lgcfu/g and 1.85 ± 0.40 vs. 1.25 ± 0.34, and there were statistical differences ( P<0.01). The CRP, TNF-α and NF-κB after treatment in combination group were significantly lower than those in control group: (12.06 ± 3.14) ng/L vs. (17.36 ± 3.08) ng/L, (10.74 ± 3.25) μg/L vs. (15.30 ± 4.18) μg/L and (1.17 ± 0.34) μg/L vs. (2.21 ± 0.82) μg/L, the IL-10 after treatment was significantly higher than that in control group: (43.14 ± 6.38) μg/L vs. (35.29 ± 5.03) μg/L, and there were statistical differences ( P<0.01). There was no statistical difference in the incidence of adverse reactions between two group ( P>0.05). Conclusions:The combined capsules of live Bifidobacterium, Lactobacillus and Enterococcus assisted triple therapy has clear efficacy in chronic gastritis children with Hp positive, with few adverse reactions. It can significantly improve clinical symptoms, and its mechanism may be related to the regulation of intestinal microbiota and serum inflammation.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Cyclosporine A, a cyclic polypeptide, exhibits potent immunosuppressive activity and exerts its effects through various mechanisms including immunosuppression, anti-inflammatory, inhibition of apoptosis, promotion of epithelial healing and goblet cell function recovery, enhancement of tear secretion, and close association with ocular surface disease repair. Owing to its significant efficacy, inhibition of disease recurrence and few side effects, the clinical application of cyclosporine A in the management of ocular surface diseases, including dry eye, corneal graft rejection following penetrating keratoplasty, vernal keratoconjunctivitis, noninfective keratitis and herpes simplex virus keratitis, has witnessed a substantial rise in recent years. Nevertheless, variations exist in the management of ocular surface inflammatory diseases when utilizing distinct concentrations and dosage forms of cyclosporine A. Therefore, the paper provides an overview of impacts of cyclosporine A on ocular surface diseases.