ObjectiveTo describe the epidemiological characteristics and trend of pulmonary tuberculosis among the elderly in Shanghai from 2014 to 2023, to estimate the incidence between 2024‒2025, so as to provide references for optimizing the prevention and control strategies of pulmonary tuberculosis for elderly in Shanghai. MethodsData of pulmonary tuberculosis patients aged ≥60 years in Shanghai registered in the Tuberculosis Registration and Management System of Chinese Center for Disease Control and Prevention from 2014 to 2023 was derived to describe the demographic characteristics of the elderly patients with pulmonary tuberculosis, and to calculate the reported incidence rate and annual percentage change (APC) of pulmonary tuberculosis. The autoregressive integrated moving average (ARIMA) model was constructed using monthly reported incidence data from January 2014 to June 2023, and data from July to December in 2023 were used to validate the model and predict the reported incidence rate of pulmonary tuberculosis among elderly in 2024 and 2025. ResultsA total of 19 208 elderly pulmonary tuberculosis patients were registered and reported in Shanghai from 2014 to 2023, with an average annual reported incidence rate of 35.04/100 000. The reported incidence rate of pulmonary tuberculosis in elderly showed an overall decreasing trend, APC=-3.34% (t=-3.360,P=0.010). While, the proportion of elderly pulmonary tuberculosis patients showed a yearly increasing trend among the total registered and reported cases, APC=5.65% (t=10.820, P<0.001). The difference in the average annual reported incidence rate of pulmonary tuberculosis in elderly was statistically significant in different regions (χ²=31.762, P=0.007), with the central urban areas(33.23/100 000) being lower than that in suburban areas (36.46/100 000), and the annual decreasing rate was faster in central urban area, APC=-4.88% (t=-4.838, P<0.001) and -2.76% (t=-2.811, P=0.023), respectively. The incidence rate was significantly higher in males than that in females (χ²=514.395, P<0.001). Additionally, the difference in reported incidence rate was statistically significant among different age groups(χ²=119.751,P<0.001), among which patients aged ≥80 years had the highest average annual incidence rate (59.69/100 000), and those aged ≤60 years had the lowest average annual incidence rate (28.57/100 000). Compared with the non-residential permanent elderly population (47.68/100 000), the average annual incidence rate of pulmonary tuberculosis among the elderly with household registration in Shanghai was lower (33.82/100 000) (χ²=24.295, P<0.001). The ARIMA (0,0,1) (0,1,1) 12 model was used to predict the incidence rate of pulmonary tuberculosis among the elderly in Shanghai in 2024 and 2025, and which was predicted to be 37.41/100 000 and 35.92/100 000, respectively. ConclusionThe reported incidence rate of pulmonary tuberculosis among the elderly in Shanghai showed an overall yearly downward trend from 2014 to 2023, but its proportion in the total number of reported pulmonary tuberculosis cases increased year by year. Prevention and control efforts should still not be slackened and emphasis should be placed on male, suburban and non-residential permanent elderly populations.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective:To explore the recurrence pattern and prognosis of cervical cancer after radical chemoradiotherapy.Methods:Clinical and follow-up data of 1 359 patients with stage Ⅰ-ⅣA (International Federation of Gynecology and Obstetrics 2009 staging) who received radical radiotherapy in Zhejiang Cancer Hospital from August 2011 to December 2017 were retrospectively analyzed. The survival and prognostic factors of 249 patients with recurrence / metastasis with detailed data were analyzed. The primary endpoint was post-recurrence / metastasis survival time. Kaplan-Meier method was used to calculate the survival rate, log-rank test was used for single factor analysis, and Cox model was used for multi-factor analysis.Results:The distant metastasis rate of 249 patients was 77.5%, and the local recurrence rate was 36.9%. According to the location of metastasis and recurrence, 56 cases with recurrence in the field of radiotherapy alone were assigned into group A, 157 cases with recurrence outside the radiation field alone were allocated into group B (56 cases with lymph node recurrence in group B1, 78 cases with blood metastasis in group B2, and 23 cases with lymph node and blood metastasis simultaneously in group B3), and 36 cases with combined recurrence and metastasis in and out of the field of radiotherapy were assigned into group C. The median survival time of patients in groups A, B1, B2, B3 and C was 13, 24, 13, 11 and 9 months, respectively (all P<0.001). According to the interval from initial diagnosis to recurrence / metastasis, 110 cases were classified in ≤1 year group, 74 cases in >1-2 years group, and 65 cases in >2 years group. The median survival time of patients in the three groups was 11, 14, and 22 months, respectively (all P<0.001). According to the management of recurrence / metastasis, 138 cases received palliative treatment, 15 cases received local treatment, 45 cases received systemic treatment, and 51 cases received combined treatment. The median survival time of patients among four groups was 9, 37, 20 and 32 months, respectively (all P<0.001). The results of multi-factor analysis showed that age, recurrence / metastatic site, retreatment methods, time interval between initial treatment and recurrence /metastasis were the independent prognostic factors affecting the survival (all P<0.05). Conclusions:Distant metastasis is the main failure pattern after radical radiotherapy. Patients with metastasis out of irradiated regions, especially those with only lymph node metastasis, have good prognosis. Active retreatment and time interval between initial diagnosis and recurrence / metastasis are important prognostic factors.

BACKGROUND:Prosthesis loosening and wear are still the main problems in the failure of total ankle replacement,which are closely related to the micro-motion of the implant-bone interface,the contact stress of the articular surface and joint motion.The design of artificial joint components,including insert and tibial/talar stem prosthesis,is a key factor affecting the force,motion,and micromotion of the contact interface of the ankle joint.The development of new inserts is of great significance to improve the survival rate of artificial ankle joints. OBJECTIVE:The finite element model of the total ankle replacement model was constructed to detect the biomechanical properties of the porous structure-optimized inserts,and the effect of the porous structure-optimized inserts on reducing prosthesis micromotion and improving the contact behavior of the articular surface was analyzed. METHODS:Based on the CT scan data of the right ankle joint of a healthy adult and the INBONE Ⅱ system product manual,a three-dimensional model including bone and artificial joint system was established,and the total ankle replacement model(model A)was obtained after osteotomy and prosthesis installation,and then through four new types of inserts,G50,G60,D50,and D60,were obtained by transforming the porous structure of the original insert,and the original one was replaced with different inserts to establish an optimized total ankle replacement model(models B-E)corresponding to the inserts.The gait loads were applied on the five models to simulate the gait conditions.The differences in micromotion and articular surface contact behaviors at the implant-bone interface of all five models were compared. RESULTS AND CONCLUSION:(1)In the gait cycle,the micromotion of the prosthesis of the four optimized total ankle replacement models was lower than that of the original model.Compared with model A,the micromotion of the prosthesis in models B-E decreased by 5.4%,10.1%,8.1%,and 20.9%,respectively.The high micromotion area of t ??he tibial groove dome in the optimized model was significantly smaller than that of the original model.(2)The four optimized models obtained a larger articular surface contact area.Compared with model A,the average contact area of t ??he inserts in models B-E increased by 11.8%,14.7%,8.1%,and 32.6%,respectively.(3)Similar to the effect of increasing the contact area,compared with the original model,the contact stress of the optimized model decreased in varying degrees,and the value of model E decreased the most significantly(P<0.05),it is due to good mechanical properties and large porosity of the Diamond lattice that constitutes the D60-type insert.(4)The research results show that the use of porous structure to improve the inserts can improve the elasticity of the inserts and increase its ability to absorb joint impact,for favorable conditions are created for reducing micromotion at the implant-bone interface and improving joint contact behavior.

Objective:To investigate the protective effect of quercetin (QR) on acute liver injury induced by diquat (DQ) poisoning in mice and its mechanism.Methods:Eighty healthy male C57BL/6 mice with SPF grade were randomly divided into control group, DQ model group, QR treatment group, and QR control group, with 20 mice in each group. The DQ poisoning model was established by a one-time intraperitoneal injection of DQ solution (40 mg/kg); the control and QR control groups received equivalent amounts of distilled water through intraperitoneal injection. Four hours after modeling, the QR treatment group and the QR control group received 0.5 mL QR solution (50 mg/kg) through gavage. Meanwhile, an equivalent amount of distilled water was given orally to the control group and the DQ model group. The treatments above were administered once daily for seven consecutive days. Afterwards, the mice were anesthetized, blood and liver tissues were collected for following tests: changes in the structure of mice liver tissue were observed using transmission electron microscopy; the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using enzyme linked immunosorbent assay (ELISA); the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured using the water-soluble tetrazolium-1 (WST-1) method, the thiobarbituric acid (TBA) method, and enzymatic methods, respectively; the protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues were detected using Western blotting.Results:Severe mitochondrial damage was observed in the liver tissues of mice in the DQ model group using transmission electron microscopy, yet mitochondrial damage in the QR treatment group showed significant alleviation. Compared to the control group, the DQ model group had significantly increased levels of MDA in liver tissue, serum AST, and ALT, yet had significantly decreased levels of GSH and SOD in liver tissue. In comparison to the DQ model group, the QR treatment group exhibited significant reductions in serum levels of ALT and AST, as well as MDA levels in liver tissue [ALT (U/L): 52.60±6.44 vs. 95.70±8.00, AST (U/L): 170.45±19.33 vs. 251.10±13.09, MDA (nmol/mg): 12.63±3.41 vs. 18.04±3.72], and notable increases in GSH and SOD levels in liver tissue [GSH (μmol/mg): 39.49±6.33 vs. 20.26±3.96, SOD (U/mg): 121.40±11.75 vs. 81.67±10.01], all the differences were statistically significant (all P < 0.01). Western blotting results indicated that the protein expressions of Nrf2 and HO-1 in liver tissues of the DQ model group were significantly decreased compared to the control group. On the other hand, the protein expressions of Keap1 and activated caspase-9 were conspicuously higher when compared to the control group. In comparison to the DQ model group, the QR treatment group showed a significant increase in the protein expressions of Nrf2 and HO-1 in liver tissues (Nrf2/β-actin: 1.17±0.08 vs. 0.92±0.45, HO-1/β-actin: 1.53±0.17 vs. 0.84±0.09). By contrast, there was a notable decrease in the protein expressions of Keap1 and activated caspase-9 (Keap1/β-actin: 0.48±0.06 vs. 1.22±0.09, activated caspase-9/β-actin: 1.17±0.12 vs. 1.59±0.30), the differences were statistically significant (all P < 0.01). Conclusion:QR may reduce acute liver injury induced by DQ poisoning in mice via activating Keap1/Nrf2 signaling pathway.

Tuberculosis （TB） and human immunodeficiency virus infection / acquired immune deficiency syndrome （HIV/AIDS） are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years， with the promotion and application of new TB and HIV detection technologies worldwide， TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening， summarizes important progress of research and applications， and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.

Objective:To analyze the characteristics of inhibitory control and cognitive flexibility in hearing-impaired children.Methods:From March to April 2023, a convenience sampling method was used to select 33 hearing-impaired children from a special education school in Meizhou City, Guangdong Province, and 35 normal-hearing children from two ordinary schools as participants. Inhibitory control and cognitive flexibility of the participants were assessed by the Flanker task and the dimensional change card sorting (DCCS) task. Statistical analysis was conducted using SPSS 26.0 software, and independent sample t-test was used to compare the differences in reaction time and accuracy rate between two groups of participants. Results:There were no significant differences in the Flanker task reaction time ((558.39±123.65) ms vs (566.11±118.20) ms) and accuracy rate((0.93±0.10) vs (0.96±0.04))between hearing-impaired children and normal-hearing children ( t=-0.295, -1.645, both P>0.05). The hearing-impaired children had significantly longer reaction time ((1 019.60±131.08) ms)than the normal-hearing children ((857.85±129.19) ms) ( t=4.046, P=0.001) in the DCCS task, while there was no statistically significant difference in the accuracy rate between hearing-impaired children (0.62±0.16) and normal-hearing children (0.57±0.15) ( t=-1.602, P>0.05). Conclusion:There is no difference in inhibitory control ability between hearing-impaired children and normal-hearing children, but the hearing-impaired children have a lag in cognitive flexibility.

Objective:To explore the clinical efficacy of the San Diego osteotomy in treating developmental dysplasia of the hip (DDH) in children.Methods:A retrospective analysis was conducted on 33 pediatric cases of posterolateral acetabular dysplasia treated with the San Diego osteotomy at the 920th Hospital of the People's Liberation Army Joint Logistics Support Force in China from August 2018 to August 2022. The cohort included 3 males (4 hips) and 30 females (36 hips), with an average age of 4.9±1.4 years (range, 2-8 years). Among these, 32 cases (38 hips) were diagnosed with DDH, and 1 case (2 hips) with paralytic dislocation of the hip. According to the T?nnis classification, 3 hips were classified as type II, 25 hips as type III, and 12 hips as type IV. The San Diego osteotomy technique was utilized to enhance the posterior lateral acetabular coverage, combined with femoral osteotomy to adjust the hip abduction, flexion, and adduction angles. Postoperative outcomes were assessed using the modified Severin radiographic classification and the McKay grading system.Results:All 33 patients were followed up for an average of 37.70±18.44 months (range, 12-74 months). No cases of postoperative hip redislocation or residual acetabular underdevelopment were observed. The hip abduction angle improved from 24.98°±3.48° at 6 weeks postoperatively to 37.28°±4.63° at the 3-month follow-up, and 64.05°±3.82° at the 6-month follow-up, with a statistically significant difference ( F=77.327, P<0.001). The hip flexion angle increased from 26.34°±5.05° at 6 weeks postoperatively to 76.53°±4.38° at 3 months, and 106.47°±2.29° at 6 months, also showing a statistically significant difference ( F=54.377, P<0.001). The hip adduction angle progressed from 1.73°±1.18° at 6 weeks postoperatively to 12.33°±1.97° at 3 months, and 29.03°±4.17° at 6 months, with a significant difference ( F=45.162, P<0.001). The McKay hip joint grading system indicated 11 excellent, 20 good, and 9 acceptable outcomes, yielding an overall excellent and good rate of 78%. The Severin radiographic grading revealed 16 hips at grade I and 24 hips at grade II. Five patients (5 hips) experienced transient vascular compromise of the femoral head at 3 months postoperatively, which resolved after a 1-month non-weight-bearing period. At the final follow-up, one patient had residual femoral head enlargement in the right hip, while the remaining 32 cases showed satisfactory ossification and remodeling of the femoral head. Conclusion:The San Diego osteotomy significantly enhances hip joint range of motion and results in satisfactory hip joint function in children with developmental dysplasia of the hip

Objective To investigate the key physical and chemical properties of nintedanib liposomes prepared by 4 different methods in order to screen out the best preparation method of nintedanib liposomes.Methods Firstly,nintedanib liposomes were prepared by thin film dispersion,reverse evaporation,ethanol injection and modified ethanol injection,respectively.The entrapment efficiency of nintedanib liposomes was then determined by dialysis and characterized for particle size,dispersibility,surface potential,and morphology.Their stability was evaluated after being placed at room temperature for 7 d.Results Circular nintedanib liposomes were respectively prepared by thin film dispersion,reverse evaporation,ethanol injection and modified ethanol injection,with a particle size of(285.1±12.3),(271.4±5.9),(226.3±14.8)and(197.2±11.2)nm,an encapsulation rate of(15.82±1.26)％,(16.71±1.35)％,(25.12±3.21)％and(32.5±3.61)％,respectively.The nintedanib liposomes prepared by modified ethanol injection had significantly smallest particle size and highest encapsulation efficiency than the liposomes by the other 3 methods(P＜0.05).In 7 d after being placed at room temperature,the particle sizes of the liposomes prepared by film dispersion and reverse evaporation were increased notably(P＜0.01),but no such change was observed in the liposomes prepared by ethanol injection and modified ethanol injection(P＞0.05).Conclusion Nintedanib liposomes prepared by modified ethanol injection have excellent key physical and chemical properties,and this method is an optical one for preparing nintedanib liposomes.

AIM:To establish and evaluate a colonoids model of intestinal barrier dysfunction with irritable bowel syndrome(IBS).METHODS:The colonic recess of 20～22 g male C57BL/6 mice were isolated and cultured in ma-trix glue to proliferate and differentiate into 3D hollow spheres with colonic epithelioid structure.The following experi-ments were carried out:(1)Colonoids and colonic tissues of mice were detected by immunofluorescence to identify colo-noids.(2)Fluorescein isothiocyanate dextran 4(FD4)evaluated the epithelial barrier function of colonoids.(3)To ex-plore the changes in the epithelial barrier of colonoids induced by interferon-γ(IFN-γ)at different concentrations and time points.FD4 and HE staining were used to evaluate the barrier function.RT-qPCR was used to detect the mRNA expres-sion of occludin and zonula occludens-1(ZO-1)in tight junctions of colonoids.Immunofluorescence was used to detect the distribution and localization of occludin and ZO-1 proteins.RESULTS:(1)The expression of EdU proliferation and in-testinal epithelial cell lineage markers in colonoids was consistent with that in mouse colonic tissues.(2)In the control group,FD4 did not infiltrate the colonoids lumen,but FD4 significantly infiltrated the colonoids lumen induced by ethyl-ene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid(EGTA).(3)From 18 h,the IFN-γ at 60,100,200 and 240 ng/mL could significantly infiltrate into the cavity of colonoids(0.033,0.032,0.042 and 0.001),and the barri-er injury of colonoids could be seen by HE staining.After 18 h,all concentrations of IFN-γ could significantly decrease the mRNA expression of occludin and ZO-1,and the fluorescence of occludin and ZO-1 decreased significantly(P<0.05).CONCLUSION:(1)The cultured organoids are colonoids with complete epithelial barrier.(2)IFN-γ could in-duce the decrease of the transcriptional levels of occludin and ZO-1 in the tight junction of colonoids,the decrease of the expression of corresponding proteins,and the change of localization and distribution,thus increasing the epithelial perme-ability of colonoids.This model is highly consistent with the pathophysiological state of IBS colonic mucosal barrier dys-function,which provides a new tool and method for studying the direction of colonic mucosal barrier dysfunction in IBS.