Objective: To analyze the epidemiological characteristics of varicella among nursery children in Shenzhen from 2015 to 2024, and to evaluate the impact of optimizing varicella vaccine (VarV) immunization strategies on varicella incidence. Methods: Varicella incidence data for nursery children in Shenzhen from 2015 to 2024 were obtained from the China Disease Prevention and Control Information System. The study period was divided into three phases:one dose self pay VarV (January 2015 to October 2017), two dose self pay VarV (November 2017 to October 2019), and two dose free VarV (November 2019 to December 2024). Interrupted time series (ITS) analysis was conducted to assess changes in the level and trend of varicella incidence associated with each phase of policy implementation. Results: A total of 27 517 varicella cases was reported among nursery children from 2015 to 2024, with an average annual incidence of 514.01/100 000. During the same period, 136 clustered outbreaks were reported in nursery institutions, involving a cumulative total of 1 091 cases. ITS analysis showed that during the self pay 1 dose stage, the varicella incidence among nursery children showed an upward trend, with an average monthly increase of 2.58/100 000 (95% CI =2.21/ 100 000 -2.95/100 000, P <0.01). After the implementation of the self pay 2 dose strategy, the incidence decreased, with a change in incidence of -26.12/100 000 (95% CI =-37.30/100 000 to -14.94/100 000) and a change in slope of -2.65/100 000 (95% CI = -3.38/100 000 to -1.93/100 000)(all P <0.01). After the implementation of the free 2 dose strategy, the incidence decreased further, with a change in incidence of -40.03/100 000 (95% CI =-50.39/100 000 to -29.66/100 000, P <0.01) and a change in slope of -0.56/100 000 (95% CI =-1.20/100 000-0.08/100 000, P =0.09). Conclusion The gradual optimization of the VarV vaccination strategy in Shenzhen from self pay 1 dose to free 2 dose has significantly reduced the varicella incidence among nursery children, demonstrating good short term control and long term intervention effectiveness.

Pathologic myopia(PM)is characterized by progressive axial elongation, posterior staphyloma, and fundus degenerative changes, representing a leading cause of blindness in Asian countries.Posterior scleral reinforcement(PSR)is currently the only surgical intervention to slow axial elongation. Its mechanisms involve mechanical reinforcement, improved blood circulation, and biological stimulation of scleral remodeling. This article reviews recent advances in PSR: surgical techniques have evolved from complex, classic procedures to standardized single-strip methods, incorporating 3D MRI to quantify posterior staphyloma morphology for personalized graft design and facilitating minimally invasive, precision surgery. Among implant materials, biomaterials such as allogeneic dura mater are being continuously optimized, while biomimetic piezoelectric smart materials actively promote scleral collagen synthesis through electrical signals, achieving a paradigm shift from “passive support”to “active reinforcement”. Clinical outcomes indicate advantages in regulating axial length, enhancing visual function and blood circulation, and facilitating early intervention in children. Combined procedures with ICL implantation, cataract surgery or vitrectomy provide comprehensive treatment regimens for individual patients with varied conditions. This article also analyzes long-term issues and core controversies including ectopic posterior staphyloma and reoperation, and prospects future research directions such as artificial intelligence assistance, translation of smart materials and full-cycle prevention and treatment systems, so as to provide references for clinical practice and scientific research.

Objective To establish models for real-time dynamic monitoring of intracellular cytoplasmic adenosine triphosphate(ATP)and mitochondrial ATP levels in cells in order to study the changes in metabolic processes.Methods The lentiviral plasmids of the cytoplasmic chemogenetic green fluorescent protein(GFP)ATP probe(Chemo-G)and those of the mitochondrial-localized chemogenetic GFP ATP probe(mito-Chemo-G)were constructed before being transfected into HEK293T together with the helper plasmids,respectively.Chemo-G and mito-Chemo-G lentiviruses were obtained.HeLa cells were infected with the lentivirus.Puromycin resistance selection and flow cytometry cell sorting were employed to identify and isolate the infected HeLa cells.The growth and GFP expressions of HeLa cells were observed.A live-cell imaging system was used for continuous imaging of the cells,with stimuli added at specific time points to alter intracellular ATP levels to observe changes in the fluorescence intensity of the ATP probe.Results Lentiviral plasmids containing Chemo-G and mito-Chemo-G sequences were constructed.Two cell lines which could stably express Chemo-G and mito-Chemo-G were established that exhibited strong growth and accurate intracellular fluorescence localization.Live-cell imaging revealed that after the addition of 2-deoxy-D-glucose(2-DG)into HeLa-Chemo-G,the fluorescence resonance energy transfer(FRET)/GFP ratio showed a decrease that was partially reversed by the addition of glucose.The FRET/GFP ratio increased after histamine stimulation,but rapidly decreased after the addition of oligomycin.Conclusion The Chemo-G and mito-Chemo-G lentiviral vectors and stably transfected cell lines HeLa-Chemo-G and HeLa-mito-Chemo-G are constructed,which provides reliable experimental models for studying cellular metabolism and changes in intracellular ATP levels.

Objective To establish a stable in vitro model of CD8+T cell exhaustion.Methods CD8+T cells were isolated and purified from the spleens of ovalbumin-specific CD8+T cell receptor(OT-I)transgenic mice and subjected to chronic antigen stimulation to induce exhaustion in vitro.Flow cytometry was employed to evaluate the expressions of exhaustion markers,secretion of effector cytokines,and transcription factor profiles in CD8+T cells.Exhausted and effector(non-exhausted)CD8+T cells were co-cultured with tumor cells before tumor cell viability was measured to assess the cytotoxic potential of CD8+T cells.Additionally,N-acetyl-L-cysteine(N-AC)was used as a positive control during exhaustion induction to validate the model.Results Chronic stimulation resulted in a significant upregulation of inhibitory receptors,including programmed cell death protein 1(PD-1),T cell immunoglobulin and mucin domain-containing protein 3(TIM-3),T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motifdomain(TIGIT),and lymphocyte activation gene 3(LAG-3).Concurrently,the secretion of key effector cytokines such as tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)was markedly reduced.Exhausted CD8+T cells exhibited diminished cytotoxicity against tumor cells compared to effector CD8+T cells.Notably,treatment with N-AC effectively restored the function of exhausted CD8+T cells and enhanced their anti-tumor activity.Conclusion This study has established an effective in vitro model for CD8+T cell exhaustion.The use of N-AC demonstrates its potential to restore functionality in exhausted CD8+T cells,underscoring the reliability and utility of this model for investigating the anti-tumor potential of exhausted T cells.

Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas with distinct clinical and pathological features. In recent years, advancements in molecular biology techniques have led to a deeper understanding of the molecular mechanisms underlying PACC. Progress in imaging, endoscopic, and molecular diagnostic technologies has improved the early detection rate of PACC. The primary treatment modalities for PACC include surgical resection, chemotherapy, targeted therapy and immunotherapy; however, the therapeutic efficacy still requires further improvement. This article reviews the current research status of PACC, covering its epidemiology, pathological characteristics, molecular alterations, diagnostic methods, and treatment strategies, and discusses the controversies and future directions in PACC research.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Objective:To analyze the spatiotemporal correlation between the surveillance data of influenza in students reported by medical institutions and school absenteeism due to illness, and evaluate the application of Bayesian Structural Time Series model (BSTS) in the prediction of school influenza epidemic.Methods:A total of 13 schools in Dapeng new district of Shenzhen were selected. The incidence data of influenza in schools in Shenzhen from January 1, 2015 to December 31, 2019 were collected from China Disease Control and Prevention Information System and the illness related school absentence data during this period were collected from Shenzhen Student Health Surveillance System, and the spatiotemporal correlation between the data from two systems was analyzed and compared. BSTS was used to make long-term predictions of the monthly incidence of influenza in students in 2019 and short-term predictions of the weekly incidence of influenza in week 1-8 and week 45-52 of 2019 by using the data from two systems.Results:There was a temporal correlation between the data from China Disease Control and Prevention Information System and the data from Shenzhen Student Health Surveillance System ( r=0.93, P<0.001), and the lag of the former one was 1 day ( r=0.73, P<0.001). Influenza outbreaks were randomly distributed in different schools in Shenzhen, and there was no spatial correlation. The root mean square error ( RMSE) and mean absolute error ( MAE) were 0.35 and 0.28, respectively, in the long-term prediction, and the RMSE was 0.33 and 0.34, and the MAE was 0.26 and 0.28, respectively, in the short-term predictions of week 1-8 and week 45-52 of 2019, respectively, showing good prediction accuracy and fitting effect. Conclusion:By analyzing the data from China Disease Control and Prevention Information System and Shenzhen Student Health Surveillance System with BSTS, the dynamics of the school influenza epidemic can be accurately predicted, and effective technical support can be provided for the early warning and prevention and control of influenza epidemic.

Objective:To analyze the temporal distribution of other infectious diarrhea (OID) in Shenzhen and provide evidence for the prevention and control of OID.Methods:The incidence data of OID in Shenzhen from 2011 to 2023 were collected. The seasonal and trend decomposition using loess (STL), seasonal index method, concentration degree and circular distribution method were used to analyze the incidence trend and temporal distribution of OID.Results:A total of 477 611 cases of OID were reported in Shenzhen from 2011 to 2023, with an average annual incidence rate of 260.19/100 000 showing a fluctuating upward trend. The seasonal index method indicated that October-January was period with high incidence of OID in Shenzhen and the seasonal intensity began to decrease in 2020. STL revealed an obvious incidence peak in winter. The concentration method showed that OID had a certain seasonality before 2018 except 2016, but the seasonality was not obvious after 2018. The circular distribution results showed that r was 0.05, mean angle ā was 1.92° and angular standard deviation s was 141.93° ( Z=1 033.37, P<0.001), with the peak on January 1 st and the high incidence period from August 11 th to May 25 th. Conclusions:OID had a certain degree of seasonality in Shenzhen, with an obvious incidence peak in winter. Since the seasonal intensity of OID decreased after 2018, the surveillance, early warning and risk assessment of OID should be continued, and prevention and control measures should be adjusted timely according to the change in the characteristics of the epidemic.

Objectives:To analyze the epidemiological characteristics and incidence trends of chronic hepatitis B in Shenzhen from 2005 to 2023, develop a prediction models with performance evaluation, explore its associations with social demographic index (SDI) and inform targeted prevention strategy development.Methods:Based on surveillance data of infectious diseases, descriptive epidemiological methods were applied to analyze the spatiotemporal and population distribution characteristics. A multifactorial prediction model integrating the SDI was established, and its predictive performance was evaluated by using data from 2020-2023. Model accuracy was evaluated by using root mean square error and mean absolute percentage error ( MAPE). The association between SDI and incidence rates was assessed through generalized linear models. Results:A total of 235 703 chronic hepatitis B cases were reported cumulatively in Shenzhen from 2005-2023, with an annual average incidence rate of 98.84/100 000. Long-term trends revealed a significant increase in the incidence from 2005 to 2019. The incidence rate was 2.48 times higher in men than in women, and the majority of cases occurred in age group 20-50 years. The cases were mainly workers in manufacturing and services. Seasonal incidence peaks were observed in March and during May to November. The overall SDI exhibited a consistent upward trend, and the positive correlation between SDI and incidence rate was observed in central urban districts (Futian and Nanshan). In contrast, industrial zones (Guangming and Bao'an) saw a significant decline in incidence rates due to intensified prevention interventions despite the increase of SDI level. Model predictions indicated that the multivariate long short-term memory (LSTM) deep learning model integrating SDI parameters outperformed both the spatiotemporal covariate- enhanced model and the augmented Bayesian structural time series model, with MAPE of 4.71%, 7.66% and 10.30%, respectively. Conclusion:SDI is a key social determinant associated with hepatitis B transmission risks, and dynamic thresholds can be established to develop tiered early warning mechanisms. It is suggested to integrate multisource SDI data into the LSTM framework, implement targeted interventions such as "rapid antibody screening in key areas + vaccination boosters for high-risk populations" and improve the timeliness of epidemic response through hybrid models to reduce disease burden level.