Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

BACKGROUND:Through scientific research addressing the effect of calcined deer antler slices on promoting the proliferation of bone marrow mesenchymal stem cells,it aims to provide empirical support for the integration and innovation of traditional Chinese medicine and modern regenerative medicine,and promote the widespread application of traditional Chinese medicine in the treatment of skeletal system diseases.OBJECTIVE:To investigate the effect of calcined deer antler slices on bone marrow mesenchymal stem cell proliferation.METHODS:Different calcination samples were prepared by wrapping deer antler slices with materials such as clay,yellow clay,and salted yellow clay,resulting in seven different samples(clay-cotton cloth,yellow clay-cotton cloth,salted yellow clay-cotton cloth,yellow clay-tin foil,salted yellow clay-tin foil,yellow clay-honey roasted,salted yellow clay-honey roasted antler slices).Water-soluble extract content in deer antler slices was determined before and after calcination.CCK-8 assay was used to evaluate the effects of different aqueous extracts of calcined antler slices on the proliferation activity of bone marrow mesenchymal stem cells.RESULTS AND CONCLUSION:(1)Calcination significantly increased the water-soluble extract content of deer antler slices,with the highest content observed in samples treated with yellow clay and honey.(2)Calcined deer antler slices significantly promoted bone marrow mesenchymal stem cell proliferation,among which the yellow clay-honey roasted deer antler slices have the most significant effect on promoting the proliferation of bone marrow mesenchymal stem cells.

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

BACKGROUND:Through scientific research addressing the effect of calcined deer antler slices on promoting the proliferation of bone marrow mesenchymal stem cells,it aims to provide empirical support for the integration and innovation of traditional Chinese medicine and modern regenerative medicine,and promote the widespread application of traditional Chinese medicine in the treatment of skeletal system diseases.OBJECTIVE:To investigate the effect of calcined deer antler slices on bone marrow mesenchymal stem cell proliferation.METHODS:Different calcination samples were prepared by wrapping deer antler slices with materials such as clay,yellow clay,and salted yellow clay,resulting in seven different samples(clay-cotton cloth,yellow clay-cotton cloth,salted yellow clay-cotton cloth,yellow clay-tin foil,salted yellow clay-tin foil,yellow clay-honey roasted,salted yellow clay-honey roasted antler slices).Water-soluble extract content in deer antler slices was determined before and after calcination.CCK-8 assay was used to evaluate the effects of different aqueous extracts of calcined antler slices on the proliferation activity of bone marrow mesenchymal stem cells.RESULTS AND CONCLUSION:(1)Calcination significantly increased the water-soluble extract content of deer antler slices,with the highest content observed in samples treated with yellow clay and honey.(2)Calcined deer antler slices significantly promoted bone marrow mesenchymal stem cell proliferation,among which the yellow clay-honey roasted deer antler slices have the most significant effect on promoting the proliferation of bone marrow mesenchymal stem cells.

Objective:This study aimed to investigate the association between early immune reconstitution and Epstein-Barr virus (EBV) reactivation by analyzing changes in natural killer (NK), B, and T cells and their functional status in the peripheral blood during the early post-transplant period.Methods:This study included 23 patients who underwent haplo-hematopoietic stem cell transplantation (HSCT). The immune reconstitution of NK cells, T cells, and B cells as well as the expression levels of NK and T cell exhaustion markers (PD-1, TIM-3, and CTLA-4) and cytotoxic function at 1, 2, and 3 months post-transplantation were compared between patients with EBV activation (EBV+ group) and those without activation (EBV- group) post- transplantation.Results:EBV activation occurred in nine patients post-transplantation (EBV+ group), whereas 14 patients demonstrated no activation (EBV- group). All patients with EBV activation exhibited EBV viremia, and no EBV-associated diseases occurred. No significant differences in the clinical characteristics were found between the two groups of patients. The median proportion of CD3 +CD8 + T cells in the EBV+ group was significantly lower than that in the EBV- group at 1 month post-transplantation ( P=0.033). The median proportion of the CD3 -CD16 negCD56 bri subset in the EBV+ group was significantly higher than that in the EBV- group at 2 months post-transplantation ( P=0.046). No significant differences in the median proportions of CD3 -CD19 + B cells were observed between the two groups at 1, 2, and 3 months post-transplantation. The expression of CTLA-4 on CD3 -CD16 briCD56 dim NK cells in the EBV+ group was significantly higher than that in the EBV- group at 1 month post-transplantation ( P=0.033). The expression of TIM-3 on CD3 +CD8 + T cells in the EBV+ group was significantly higher than that in the EBV- group ( P=0.009). The expression level of TIM-3 on CD3 -CD16 negCD56 dim NK cells in the EBV+ group was significantly lower than that in the EBV- group at 2 months post-transplantation ( P=0.023). The expression levels of TIM-3 on CD3 +CD4 + T cells in the EBV+ group than those in the EBV- group at 1 and 3 months post-transplantation ( P=0.002, P=0.043). The median positive rate of Granzyme B expression in CD3 +CD8 + T cells and CD3 +CD4 + T cells in the EBV+ group was significantly lower than that in the EBV- group at 1-month post-transplantation ( P=0.033, P=0.016). The median positive rate of Granzyme B expression in the CD3 -CD16 briCD56 neg cell subset in the EBV+ group was higher than that in the EBV- group at 2 months post-transplantation ( P=0.012). The median positive rate of Granzyme B expression in CD3 +CD4 + T cells in the EBV+ group remained significantly lower than that in the EBV- group at 2 months post-transplantation ( P=0.049). The median positive rate of perforin expression in the CD3 -CD16 briCD56 dim cell subset was significantly higher in the EBV+ group than in the EBV- group at 3 months post-transplantation ( P=0.003). The median positive rate of IFN-γ expression in CD3 +CD8 + T cells in the EBV+ group was significantly lower than that in the EBV- group at 3 months post-transplantation ( P=0.036) . Conclusion:Delayed NK cell and T lymphocyte reconstitution, high exhaustion marker expression, and weakened cytotoxic functions may be related to EBV reactivation after haploidentical HSCT.

Objectives:To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared.Results:A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods ( P=0.008) . Conclusions:mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.

Objective:To investigate the prognostic value of albumin (ALB), aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT) in patients with acute liver failure (ALF) in hyperacute phase of sepsis which provided the basis for clinical evaluation and prognostic judgment and corresponding treatment options.Methods:A multicenter retrospective cohort study was conducted. Patients with ALF in hyperacute phase of sepsis admitted to Zhoupu Hospital Affiliated to Shanghai Health College, Shanghai Pudong New Area People's Hospital, and Shanghai Oriental Hospital from January 2019 to February 2024 were enrolled. General data such as gender and age of the patients were collected. Lactate dehydrogenase (LDH), liver function indexes [total bilirubin (TBIL), direct bilirubin (DBIL), AST, ALT, AST/ALT, ALB, total protein (TP), globulin (GLB), ALB/GLB ratio (A/G), blood amine, γ-glutamyl transpeptidase (γ-GT)], platelet count (PLT), creatinine, activated partial thromboplastin time (APTT), severity of illness scores [acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), sequential organ failure assessment (SOFA)], serum procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), arterial blood lactic acid (Lac) within 24 hours after admission, and whether to use mechanical ventilation, whether to use vasoactive drugs, whether to use artificial liver treatment and prognosis during hospitalization also were collected. The differences of clinical data between patients with different prognosis were compared. The variables with statistically significant differences in univariate analysis were included in multivariate Logistic regression analysis to determine the independent risk factors for death of patients with ALF in hyperacute phase of sepsis during hospitalization. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of ALB and AST/ALT for death of patients with ALF in hyperacute phase of sepsis during hospitalization.Results:A total of 73 patients with ALF in hyperacute phase of sepsis were included, with 22 survived and 51 died during hospitalization and the mortality of 69.86%. Compared with the survival group, the patients in the death group had lower ALB, γ-GT within 24 hours after admission and proportion of artificial liver treatment, and higher AST/ALT, SOFA score, LDH and proportion of use of vasoactive drugs. The differences were statistically significant. Multivariate Logistic regression analysis showed that ALB and AST/ALT were the independent risk factors for death in patients with ALF in hyperacute phase of sepsis during hospitalization [ALB: odds ratio ( OR) = 0.856, 95% confidence interval (95% CI) was 0.736-0.996, P = 0.044; AST/ALT: OR = 2.018, 95% CI was 1.137-3.580, P = 0.016]. ROC curve analysis showed that the area under the curve (AUC) of ALB for predicting in-hospital death in patients with ALF in hyperacute phase of sepsis was 0.760 (95% CI was 0.637-0.884, P < 0.001). When ALB ≤ 29.05 g/L, the sensitivity was 68.2%, and the specificity was 76.5%. The AUC of AST/ALT for predicting in-hospital death in patients with ALF in hyperacute phase of sepsis was 0.764 (95% CI was 0.639-0.888, P < 0.001). When AST/ALT ≥ 1.26, the sensitivity was 59.1%, and the specificity was 90.2%. Conclusions:The lower the ALB level, and the higher the AST/ALT within 24 hours after admission, the worse the prognosis of patients with ALF in hyperacute phase of sepsis. ALB and AST/ALT can be used as clinical indicators to evaluate the severity and prognosis of patients with ALF in hyperacute phase of sepsis.

Background At present, the practice of pulmonary rehabilitation for pneumoconiosis in China is in a primary stage. The basis for formulating an individualized comprehensive pulmonary rehabilitation plan is still insufficient, which is one of the factors limiting the development of community-level rehabilitation work. Objective To formulate an exercise prescription based on maximum heart rate measured by cardiopulmonary exercise test (CPET), conduct an individualized comprehensive pulmonary rehabilitation program with the exercise prescription for patients with stable pneumoconiosis, and evaluate its role in improving exercise endurance and quality of life, thus provide a basis for the application and promotion of pulmonary rehabilitation. Methods A total of 68 patients were recruited from the Occupational Disease Prevention Hospital of Jinneng Holding Coal Industry Group Co., Ltd. from April to August 2022 , and were divided into an intervention group and a control group by random number table method, with 34 cases in each group. All the pneumoconiosis patients participated in a baseline test. The control group was given routine drug treatment, while the intervention group received multidisciplinary comprehensive pulmonary rehabilitation treatment on the basis of routine drug treatment, including health education, breathing training, exercise training, nutrition guidance, psychological intervention, and sleep management, whose exercise intensity was determined according to the maximum heart rate provided by CPET. The rehabilitation training lasted for 24 weeks. Patients were evaluated at registration and the end of study respectively. CPET was used to measure peak oxygen uptake per kilogram (pVO₂/kg), anaerobic threshold (AT), carbon dioxide equivalent of ventilation (EqCO₂), maximum metabolic equivalent (METs), and maximum work (W_max). The modified British Medical Research Council Dyspnea Questionnaire (mMRC), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), and Short Form of Health Survey (SF-36) were used to evaluate the potential effect of the comprehensive pulmonary rehabilitation program. Results Among the included 68 patients, 63 patients were having complete data, then 31 cases were assigned in the control group and 32 cases in the interventional group. Before the intervention, there was no significant difference in pVO₂/kg, AT, EqCO₂, METs, or W_max between the two groups (P>0.05). At the end of the trail, the indicators like pVO₂/kg [(19.81±2.38) mL·(min·kg)⁻¹], AT [(14.48±2.33) mL·(min·kg)⁻¹], METs (5.64±0.69), and W_max [(85.25±14) W] of patients in the intervention group were all higher than those [(13.90±2.37) mL·(min·kg)⁻¹, (11.70±1.94) mL·(min kg)⁻¹, (3.97±0.70), and (61.77±14.72) W, respectively] in the control group (P<0.001); there was no significant difference in EqCO₂ between the two groups (P=0.083). Before the trial, there was no significant difference in mMRC, SAS, SDS, PSQI, or CAT scores between the two groups (P>0.05). At the end of the trail, the mMRC score (1.16±0.57), SAS score (27.93±2.12), SDS score (26.48±1.44), PSQI score (1.08±0.88), and CAT score (4.34±3.28) of patients in the intervention group were lower than those [(2.03±0.83), (35.87±6.91), (34.23±6.65), (5.37±3.03), and (13.87±7.53), respectively] in the control group (P<0.001). The SF-36 scores of bodily pain (94.13±10.72), general health (87.50±5.68), vitality (95.31±5.53), mental health (99.88±0.71), and health changes (74.22±4.42) in the intervention group were higher than those [(71.87±32.72), (65.81±15.55), (74.52±16.45), (86.97±16.56), and (29.84±13.50), respectively] in the control group (P<0.001), and no significant difference was found in social functioning and role emotional scores (P>0.05). Conclusion Comprehensive pulmonary rehabilitation can increase the oxygen intake and exercise endurance of pneumoconiosis patients, ameliorate dyspnea symptoms, elevate psychological state and sleep quality, and improve the quality of life.

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. Objective To study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. Methods Patients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. Results There was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. Conclusion The metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.