Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

AIM: To evaluate the efficacy of high-intensity focused ultrasound cyclo plasty(UCP)in the treatment of glaucoma and to investigate related influencing factors.METHODS: The study involved a total of 110 patients(134 eyes)who received UCP treatment between January 2019 and January 2022 at three medical centers: Tianjin Eye Aier Eye Hospital, Chongqing Aier Eye Hospital, and Chongqing Nanping Aier Eye Hospital. Patients were classified into three categories: primary angle-closure glaucoma, primary open-angle glaucoma, and secondary glaucoma. Best corrected visual acuity, intraocular pressure, and the usage of anti-glaucoma medications, etc., were recorded at 6 and 12 mo postoperatively.RESULTS: After 6 months of the UCP procedure, statistically significant differences in intraocular pressure were observed across all groups(all P<0.05). At 12 mo postoperatively, intraocular pressure of the primary angle-closure and primary open-angle glaucoma groups showed differences(all P<0.05). Notably, there were no significant changes in visual acuity at either the 6 or 12 mo compared to preoperative values across all patient groups(all P>0.05). Furthermore, the study identified a statistically significant correlation between the changes in intraocular pressure at 6 mo and factors such as age, history of previous glaucoma surgery, baseline white-to-white(corneal diameter), and the extent of UCP treatment(all P<0.05).CONCLUSION: The UCP procedure has been demonstrated to effectively lower intraocular pressure in patients with glaucoma. The efficacy appears to be influenced by variables including patient age, previous glaucoma surgery history, baseline white-to-white(corneal diameter), and the scope of UCP treatment. Importantly, UCP treatment did not adversely affect visual acuity, underscoring its favorable safety profile.

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.

Objective: To investigate the prevalence and influencing factors of chronic diseases among cured leprosy patients in Huai'an City, so as to provide insights into chronic diseases control among cured leprosy patients. Methods: All cured leprosy patients in Huai'an City in 2021 were enrolled from the National Leprosy Management Information System in China. The demographic data, family status, leprosy diagnosis and treatment, health status and development of chronic diseases were collected using face-to-face questionnaire surveys and physical examinations, and the factors affecting the development of chronic diseases were identified among cured leprosy patients using a multivariable logistic regression model. Results: Totally 708 cured leprosy patients were included, with a male to female ratio of 2.75︰1, and a mean age of (71.84±10.09) years. The overall prevalence of disability was 48.45%. The prevalence of chronic diseases was 31.78% among participants, and the prevalence rates of hypertension, diabetes, coronary heart disease, stroke, dyslipidemia, tumor, chronic obstructive pulmonary diseases were 25.14%, 4.10%, 3.67%, 3.67%, 2.26%, 2.26% and 0.85%, respectively. There were 154 participants with a type of chronic diseases (21.75%), 61 with two types of chronic diseases (8.62%) and 10 with 3 and more types of chronic diseases (1.41%). Multivariable logistic regression analysis identified complete loss of labor ability (OR=1.484, 95%CI: 1.015-2.171), labor income as the major economic source (OR=0.621, 95%CI: 0.407-0.948), being cared of (OR=1.832, 95%CI: 1.203-2.788) and disability (OR=1.715, 95%CI: 1.127-2.608) as factors affecting the development of chronic diseases among cured leprosy patients. Conclusions There is a high risk of chronic diseases among cured leprosy patients with loss of labor ability, with government subsidy and others' funding as the major economic source, requiring to be cared of and with disability in Huai'an City.

Objective To study patient delay and the influencing factors of the elderly patients with pulmonary tuberculosis（PTB），so as to provide evidence for developing effective prevention and control strategies. Methods Derived the information from PTB management information system in 2010-2019 of the tuberculosis patients who were aged 60 years or older in Huai'an City, described and analyzed the influencing factors of patient delay. Results The median time of PTB patients delay in Huaian was 21 day, while the rate was 65.91%. Multivariate logistic regression analysis results showed that compared with permanent residents, city dwellers, the first diagnosis unit specialized hospital, and the patient source referral, the patient delay risks of the floating residents（OR = 2.942 , 95% CI: 2.461-3.518）, the country dwellers（OR = 1.528,95% CI :1.377-1.697）, the first diagnosis unit general hospital（OR = 1.203,95% CI: 1.087-1.333）, and the patient source recommendation （OR = 2.395,95% CI: 1.960-2.928）were higher, Compared with the peasants（OR = 0.315 , 95% CI : 0.213-0.512）, new patients（OR = 0.812 , 95% CI : 0.689-0.974） and sputum smear positive patients（OR = 0.866 , 95% CI : 0.780-0.962）, the patient delay risks of the non-peasants, recurrent patients, and sputum negative patients were lower. Conclusion The patient delay of the elderly patients with pulmonary tuberculosis（PTB）in Huaian was serious, the influencing factors of patient delay were type of household registration, current residence, occupation, type of first-time unit, source of patient , classification of treatment, and the sputum test results.

Objective: To investigate the distribution and proportion of M1/M2 macrophages in the periodontal tissues of rats with and without periodontitis. Method: Twelve Sprague-Dawley rats were randomly divided into a chronic periodontitis group (CP, n = 6) and a periodontal health group (PH, n = 6). The periodontitis model was induced at the first mandibular molar using a stainless steel ligature and was confirmed by histological analysis. M1 macrophages were labeled with inducible nitric oxide synthase (iNOS), and M2 macrophages were labeled with CD163. The distributions of M1 and M2 macrophages in the two groups were determined via immunohistochemistry and immunofluorescence, and the M1/M2 ratios were compared between the two groups. Results : The M1 type macrophage count in the PH group was 12.17 ± 1.40, and the M1 macrophage count in the CP group was 40.00 ± 3.20; there was a statistically significant difference between the two groups (t = 7.96, P＜0.0001). The M2 macrophage count in the PH group was 4.50 ± 1.09, and the M2 type macrophage count in the CP group was 5.33 ± 0.67. There was no statistically significant difference between the two groups (t = 0.65, P = 0.53). The M1/M2 ratio in the CP group was 3.72 ± 1.08, and the M1/M2 ratio in the PH group was 8.31 ± 1.37; there was a statistically significant difference between the two groups (t = 2.63, P= 0.025). Conclusion During periodontitis, M1 macrophages increased significantly and were widely distributed; they may be involved in the progression of periodontitis and may be closely related to the destruction of the cementum.

This study was aimed to analyze the pathogen distribution,drug resistance and traditional Chinese medicine (TCM) syndrome of patients with primary nephrotic syndrome complicated with pulmonary infection for the guidance of clinical practice.The clinical data of 180 patients with primary nephrotic syndrome complicated with pulmonary infection were analyzed.The results showed that among 180 patients,117 were male,accounting for 65％;73.33％ of them were over 40 years old.Membranous nephropathy was the most common pathological type,accounting for 40％.Gram-negative bacteria were the main pathogen,accounting for 51.72％.The drug resistance rates of piperacillin/tazobactam,imipenem,amikacin,gentamicin were the lowest.The drug resistance rates of third generation of cephalosporins and quinolone antibiotics were in the middle.In TCM syndrome differentiation,central qi deficiency and phlegm syndrome occupied the highest proportion,accounting for 25.56％;and the phlegm heat in the lung syndrome,accounting for 17.78％;wind evil attacking the lung syndrome,accounting for 13.33％;qi deficiency and phlegm syndrome,accounting for 9.45％;qi deficiency,blood stasis and water stagnation syndrome,accounting for 8.89％;the mixture of deficiency and excess syndrome,accounting for 59.45％,with qi deficiency as the main part.It was concluded that middle-aged and older men,pathologic type of membranous nephropathy had the higher rate of suffering pulmonary infection.Gram-negative bacteria were the main pathogen.The choice of antibiotics should be based on piperacillin/tazobactam,and third generation of cephalosporins.Qi deficiency and phlegm syndrome was the most common TCM syndrome.

Objective : To compare the inflammatory reaction of peritoneal macrophage after Pg-LPS stimulated in healthy rabbit and hyperlipidemia rabbit. Methods : 12 New Zealand rabbits were randomly divided into 2 groups with 6 rabbits in each group, and normal diet and high-fat diet were fed to them respectively. The hyperlipidemia model was set up after 6 weeks. The peritoneal macrophage in normal and hyperlipidemia group were isolated and cultured, and then the cells in both groups were respectively divided into 3 groups: control, 1 μg/mL Pg-LPS, and 1 μg/mL E.coli-LPS. After 24 h treatment, the expressions of C-reaction protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6) , interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were detected by realtime PCR. Results : The levels of CRP, IL-1β, IL-6, IL-8, and TNF-α were higher in hyperlipidemia control group than normal control group. The expressions of inflammatory substances were increased after stimulated by Pg-LPS, and statistically higher in hyperlipidemia rabbit group than normal group (P < 0.05). Conclusion Pg-LPS can enhance the mRNA expressions of inflammation related factors in peritoneal macrophage in hyperlipidemia rabbit.

Objective To explore significance of alpha‐fetoprotein isoform L2(AFP‐L2) in the screening of Down syndrome in pregnant women ,so as to provide references for clinical application .Methods A total of 250 healthy pregnant women and 22 preg‐nant women with Down syndrome were enrolled in this study .Serum specimens were collected and AFP‐12 was separated and cap‐tured by using the magnetic bal ,time‐resolved fluorescence immunoassay was used to detect levels of AFP and AFP‐L2 ,and the percentage of AFP‐L2 (AFP‐L2% ) was calculated .Results The serum level of AFP of pregnant women with Down syndrome [(20.2±4.2)ng/mL]was lower than that of healthy pregnant women[(46.7±19.9)ng/mL],and had statistically significant difference(P<0 .05) .Serum AFP‐L2% of pregnant women with Down syndrome was higher than that of healthy pregnant women , and had statistically significant difference(P<0 .05) .Conclusion Detection of AFP level and AFP‐L2% could be an indicator for Dow n syndrome screening .

Objective To discuss the MRI findings of common complications following hip arthroplasty and their association with operative and pathological findings to improve the early diagnosis and etiological differential diagnosis for common complications following hip arthroplasty. Methods Forty-six patients with hip arthroplasty complication were included in this study. We observed prosthesis location, signal changes between prosthesis and bone, and periprosthesis signal changes, signal changes of articular capsule, adjacent soft tissue and bone on MR images. Diagnostic value of MRI in detecting hip arthroplasty complication was evaluated with operative and pathological findings as reference standard. Results Complications following hip arthroplasty included aseptic loosening (n=26), osteolysis (n=12), infection (n=12), heterotopic ossification (n=4), pseudoneoplasm (n=4) and periarthroplasty fracture (n=1). The MRI finding suggestive of aseptic loosening in 24 cases was a smooth intermediate signal intensity layer along the interface. Osteolysis is seen as soft tissue signal intensity material replacing normal high signal intensity fatty marrow in 12 cases. Bone marrow edema, bone destruction, fluid collection, estracapsular collections, periprosthetic muscle edema, and sinus were predictors of infection. On MRI, mature heterotopic ossification had the appearance of cancellous bone in 5 cases. Pseudoneoplasm represents fluid signal intensity with intermediate signal intensity pseudocapsule in 5 cases. Periprosthetic fracture included hypointesense fracture lines, periosteal reaction, and periprosthetic muscle edema in one patient. Conclusion MRI is useful in detecting osseous and soft-tissue abnormalities in patients with hip implants.