BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.

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.

ObjectiveTo investigate the relationship between mitochondrial DNA copy number (mtDNAcn) and cognitive dysfunction, and its mediating role between type 2 diabetes mellitus (T2DM) and cognitive dysfunction. MethodsA case-control study was conducted from May 2019 to April 2021 at the Shanghai Yangpu District Central Hospital, China. A total of 193 subjects were recruited and divided into two groups based on the Montreal Cognitive Assessment (MoCA): normal control (NC) group (n=95) and cognitive impairment group (n=98). The prevalence of T2DM was determined on the basis of medical history, while mtDNAcn in peripheral blood samples was quantified using realtime fluorescent quantitative polymerase chain reaction. ResultsUnivariate analyses revealed that the mean mtDNAcn in the cognitive impairment group was 0.76±0.37, significantly lower than that in the NC group (1.06±0.45) (P<0.05). Logistic regression analyses showed that higher mtDNAcn was associated with a reduced risk of cognitive impairment (OR=0.315, 95%CI: 0.125‒0.795). Additionaly, a statistically significant positive correlation was observed between mtDNAcn and the total MoCA score (r=0.381, P<0.01). Morever, T2DM history (OR=2.741, 95%CI: 1.002‒7.497) and elevated glycosylated hemoglobin (HbA1c) levels (OR=1.796, 95%CI: 1.190‒2.711) were identified as risk factors for cognitive impairment. Mediation analyses indicated that mtDNAcn served as a mediator between T2DM/HbA1c and the risk of cognitive impairment, with proportions of mediating effect of 9.04% and 9.18%, respectively. ConclusionPatients with mild and moderate cognitive impairment have significantly lower mtDNAcn than those with normal cognitive function. Reduced mtDNAcn is an influencing factor for cognitive dysfunction and may play a mediating role in the association between T2DM and mild to moderate cognitive impairment.

Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder characterized by recurrent episodes of subcutaneous and submucosal edema, which can be life-threatening in severe cases. Lanadelumab, a recombinant human monoclonal antibody against kallikrein, has been recommended as a first-line option for long-term prophylaxis of HAE. This paper analyzed the clinical data of four patients with HAE diagnosed and treated with lanadelumab for long-term prophylaxis in our department since 2020. It also reviewed relevant literature, summarizing the clinical manifestations of HAE, as well as the efficacy and safety of lanadelumab in treating HAE, to provide therapeutic references for clinicians.

Objective: To investigate the trend in disease burden of interstitial lung disease (ILD) in China from 1990 to 2021, so as to provide a reference for formulating prevention and control strategies for chronic respiratory diseases. Methods: Based on the Global Burden of Disease 2021 database, data on the number of incident cases, incidence, standardized incidence, number of deaths, mortality, standardized mortality, number of disability-adjusted life years (DALY), DALY rate, and standardized DALY rate of ILD in China were collected. The incidence, mortality, and DALY rate were used to analyze the disease burden of ILD. The estimated annual percentage change (EAPC) was employed to assess the trend in standardized incidence, standardized mortality, and standardized DALY rate of ILD from 1990 to 2021. Rate decomposition analysis was applied to identify the main contributing factors affecting the trend in disease burden. Results: In 2021, China reported 48 514 cases, 7 674 deaths, and 222 288 person-years of DALY due to ILD, representing increases of 155.43%, 159.70%, and 97.34%, respectively, compared with 1990. From 1990 to 2021, the standardized incidence and standardized mortality of ILD in China showed upward trends (EAPC=1.106% and 0.239%, both P<0.05), while the standardized DALY rate showed a downward trend (EAPC=-0.230%, P<0.05). From 1990 to 2021, the standardized incidence and standardized mortality among males showed upward trends (EAPC=1.199% and 0.520%, both P<0.05), while the trend in the standardized DALY rate was not statistically significant (P>0.05). Among females, the standardized incidence of ILD showed an upward trend (EAPC=0.966%, P<0.05), while the standardized mortality and standardized DALY rate showed downward trends (EAPC=-0.306% and -0.760%, both P<0.05). In 2021, the incidence, mortality, and DALY rate of ILD in China increased with age, peaking in the group aged ≥95 years at 14.84/105, 13.90/105, and 124.71/105, respectively. Across all age groups aged ≥55 years, the incidence, mortality, and DALY rate of ILD were consistently higher in males than in females. The increase in the number of incident cases, deaths, and DALY due to ILD in China from 1990 to 2021 was primarily influenced by population aging, with contribution rates of 42.65%, 68.25%, and 69.79%, respectively. Conclusions From 1990 to 2021, the incidence and mortality risk of ILD in China showed upward trends, while the disability risk demonstrated a downward trend. Males bore a heavier disease burden of ILD, and aging was identified as the primary factor contributing to the increased burden of ILD in China.

Objective: To investigation and analyze the causes and characteristics of a food poisoning incident caused by Clostridium perfringens in schools, so as to provide a reference for prevention and control of food poisoning incidents. Methods: From March 11 to 12,2024,on site epidemiological and hygienic investigations were conducted by using food poisoning case questionnaires and on site hygienic investigation forms in Shenzhen. Information related to the poisoning incident was collected through field investigations and telephone interviews. A case control study was used to analyze the suspected food responsible for the incident. Risk analysis in χ 2 analysis was used to obtain OR values. Results: The Clostridium perfringens food poisoning incident involved two schools, with a cumulative total of 52 cases. School A had an attack rate of 2.21%(45/2 040), school B had an attack rate of 1.29% (7/544). The main clinical symptoms were diarrhea (100.00%) and abdominal pain (84.62%), with a minority experiencing fever ( 3.85 %). Analysis via the case control study indicated that consuming mushroom and meat sauce during lunch on March 11, 2024, was a risk factor for the poisoning incident ( OR =124.50, 95% CI =14.53-937.51, P <0.05). On site investigation revealed that the mushroom and meat sauce provided by the schools on March 11 was prepared by the catering company the previous day, stored without refrigeration, and not reheated before serving the next day. A total of 31 patient anal swabs, 16 food samples, and 14 kitchen staff anal swabs were sent for laboratory testing. Clostridium perfringens was isolated from 22 case samples. Among these, type A Clostridium perfringens (alpha toxin) was detected in 8 case samples, 4 kitchen staff anal swabs, and 2 retained samples of the mushroom and meat sauce. Conclusions The incident is a food poisoning outbreak caused by Clostridium perfringens contamination in schools. Avoiding cross contamination and ensuring proper storage are key to preventing Clostridium perfringens food poisoning.

Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

Objective To compare the incidence of catheter-related venous thrombosis between midline catheters and peripherally inserted central catheters.Methods Randomized controlled trials and cohort studies on the incidence of venous thrombosis associated with midline catheters and PICC catheters were searched from CNKI,Wanfang database,VIP database,Web of Science,PubMed,Embase and Cochrane Library from inception to December 31,2022.Review Manager 5.4 software and Stata 14.0 software were used to analyse and describe the outcome indicators.Results A total of 16 studies were included,including 12 cohort studies and 4 randomized controlled studies,with 21853 subjects.The results of the Meta-analysis showed that the incidence of catheter-related venous thrombosis per thousand catheter days of midline catheters was statistically significant compared with PICC[RR=2.74,95％CI(1.21,6.21),P=0.016].There was no significant difference in the incidence of catheter-related venous thrombosis compared with PICC[RR=0.85,95％CI=(0.70,1.03),P=0.101].In the subgroups,the incidence of superficial vein thrombosis in the midline catheter was significantly different from that in the PICC[RR=2.36,95％C/=(1.56,3.58),P＜0.001].Conclusion The current evidence shows that the incidence rate of catheter-related venous thrombosis per thousand catheter days and superficial vein thrombosis was higher for midline catheters than PICCs.Therefore,in clinical practice,vascular access devices should be selected reasonably,and the occurrence and development of catheter-related superficial venous thrombosis should be paid attention to,and clinical screening should be effectively carried out on the basis of a full evaluation.

Objective:To assess the efficacy of different fusion strategies involving the convolutional block attention module (CBAM) and Unet for automatic pancreas segmentation in enhanced CT images of patients with acute pancreatitis.Methods:A retrospective analysis was conducted on 1 158 patients with acute pancreatitis admitted to the Affiliated Hospital of North Sichuan Medical College between January 1st, 2016 and July 30th, 2021. Among them, 141 patients with first-episode acute pancreatitis were randomly categorized into mild, moderate, and severe cases. The test set comprised 5 mild and 15 severe cases, while the remaining 126 cases were used for training. Within the training set, 20% of the data was randomly allocated as the validation set. Different fusion paths of the CBAM and Unet networks were trained, utilizing the Dice similarity coefficient, Hausdorff distance (HD), and pixel accuracy (PA) as evaluation metrics. The model demonstrating the best performance on the validation set was selected and evaluated on the test set. Additionally, the Unet model was combined with the attention gate attention mechanism (AttentionUnet) in the skip connection, and the ResBlock replaced the original convolution module (ResUnet) in the Unet network. Moreover, the skip connection branch module of feature extraction was integrated with CBAM (ResUnet_CBAM) for comparison.Results:Unet_CBAM achieved better results on the test set with a Dice value of 80.06%, a HD value of 3.765 9 and a PA value of 0.992 3, all surpassing other fusion strategies. The segmentation accuracy of the pancreatic region in CT images of acute pancreatitis patients was notably enhanced compared to Unet and its related variant networks.Conclusions:The Unet network integrated into CBAM after skip connection can better perform pancreatic segmentation on enhanced CT images of patients with acute pancreatitis and can effectively improve the efficiency of relevant personnel in pancreatic segmentation on enhanced CT images of patients with acute pancreatitis.