BACKGROUND:The prevalence of osteoporosis is high in postmenopausal women,but muscle mass,grip strength,and how these factors affect osteoporosis are understudied,and the exact link between them has not been clarified.OBJECTIVE:To investigate the correlation between muscle mass,grip strength,appendicular skeletal muscle index and bone mineral density in postmenopausal women with osteoporosis and to assess the potential values of these indices in predicting and diagnosing postmenopausal osteoporosis.METHODS:Eighty-three postmenopausal women were collected from the outpatient clinic of the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from February 2023 to January 2024.General data were collected.Bone mineral density was detected.T-value,muscle mass of each part,grip strength were recorded.The body mass index and appendicular skeletal muscle index were calculated.The patients were categorized into non-osteoporosis group(n=17)and postmenopausal osteoporosis group(n=66)according to T value and fracture history,and were statistically analyzed accordingly.RESULTS AND CONCLUSION:(1)The body mass,body mass index,bone mineral density of the overall lumbar spine,muscle mass and appendicular skeletal muscle index were higher in the non-osteoporosis group than the osteoporosis group(P＜0.05).(2)Muscle mass was positively correlated with bone mineral density of the overall lumbar spine and individual vertebrae(P＜0.05).(3)Multiple stepwise linear regression analysis showed that body mass and grip strength were linearly and positively correlated with muscle mass;body height and muscle mass were linearly and positively correlated with grip strength,and body mass was linearly and negatively correlated with grip strength.Body mass index was linearly and positively correlated with bone mineral density,and age was linearly and negatively correlated with bone mineral density.(4)Analysis by receiver operating characteristic curve showed that:muscle mass(the area under the curve,sensitivity,specificity and critical value of muscle mass were 0.744,76.50％,74.20％and 36.50 kg,respectively,with P=0.002)and appendicular skeletal muscle index(the area under the curve,sensitivity,specificity and critical value of appendicular skeletal muscle index were 0.739,82.40％,62.10％and 5.81 kg/m2,respectively,and P=0.002)had good predictive value for postmenopausal osteoporosis.To conclude,a reduction in muscle mass and appendicular skeletal muscle index can help to predict the risk of postmenopausal osteoporosis,and the possibility of osteoporosis should be taken into account in postmenopausal women when muscle mass is＜36.50 kg or appendicular skeletal muscle index is＜5.81 kg/m2,in order to prevent the occurrence of postmenopausal osteoporosis.

BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

BACKGROUND:The prevalence of osteoporosis is high in postmenopausal women,but muscle mass,grip strength,and how these factors affect osteoporosis are understudied,and the exact link between them has not been clarified.OBJECTIVE:To investigate the correlation between muscle mass,grip strength,appendicular skeletal muscle index and bone mineral density in postmenopausal women with osteoporosis and to assess the potential values of these indices in predicting and diagnosing postmenopausal osteoporosis.METHODS:Eighty-three postmenopausal women were collected from the outpatient clinic of the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from February 2023 to January 2024.General data were collected.Bone mineral density was detected.T-value,muscle mass of each part,grip strength were recorded.The body mass index and appendicular skeletal muscle index were calculated.The patients were categorized into non-osteoporosis group(n=17)and postmenopausal osteoporosis group(n=66)according to T value and fracture history,and were statistically analyzed accordingly.RESULTS AND CONCLUSION:(1)The body mass,body mass index,bone mineral density of the overall lumbar spine,muscle mass and appendicular skeletal muscle index were higher in the non-osteoporosis group than the osteoporosis group(P＜0.05).(2)Muscle mass was positively correlated with bone mineral density of the overall lumbar spine and individual vertebrae(P＜0.05).(3)Multiple stepwise linear regression analysis showed that body mass and grip strength were linearly and positively correlated with muscle mass;body height and muscle mass were linearly and positively correlated with grip strength,and body mass was linearly and negatively correlated with grip strength.Body mass index was linearly and positively correlated with bone mineral density,and age was linearly and negatively correlated with bone mineral density.(4)Analysis by receiver operating characteristic curve showed that:muscle mass(the area under the curve,sensitivity,specificity and critical value of muscle mass were 0.744,76.50％,74.20％and 36.50 kg,respectively,with P=0.002)and appendicular skeletal muscle index(the area under the curve,sensitivity,specificity and critical value of appendicular skeletal muscle index were 0.739,82.40％,62.10％and 5.81 kg/m2,respectively,and P=0.002)had good predictive value for postmenopausal osteoporosis.To conclude,a reduction in muscle mass and appendicular skeletal muscle index can help to predict the risk of postmenopausal osteoporosis,and the possibility of osteoporosis should be taken into account in postmenopausal women when muscle mass is＜36.50 kg or appendicular skeletal muscle index is＜5.81 kg/m2,in order to prevent the occurrence of postmenopausal osteoporosis.

BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Non-small cell lung cancer(NSCLC) is one of the major histopathological types of lung cancer, accounting for about 85 percent of all lung cancers. The human epidermal growth factor receptor 2 (HER-2) alteration in NSCLC include gene mutations, gene amplifications, and protein overexpression, and is one of the important driving target. Currently, the treatment options for HER-2 altered NSCLC are still relatively limited, and more effective drugs are urgently needed. Antibody-drug conjugates (ADCs) are a highly efficient combination of targeted monoclonal antibodies and cytotoxic drugs that enable precision therapy for tumors. This paper discusses the current status of treating HER-2 variant NSCLC and the research progress of ADCs in HER-2 variant NSCLC, as well as their development prospects in NSCLC.

A Salmonella bacteriophage,PJN025,was isolated from wastewater and characterized for its biological properties,including whole-genome sequencing and assessment of therapeutic poten-tial in animal infection models.Transmission electron microscopy classified it within the Caudovi-ricetes family.PJN025 selectively lysed S.typhimurium and S.enteritidis with an incubation period of approximately 10 min,a burst time of 80 min,and an average burst size of approximately 132 PFU/cell,demonstrating effective bactericidal activity.The phage showed robust stability at temperatures ranging from 30 to 70 ℃ and pH levels from 3 to 12.Whole-genome sequencing re-vealed a complete genome length of 46 478 bp with a G+C content of 45.9％,consisting of 82 open reading frames and one tRNA.No known virulence or resistance genes were found.In Galleria mellonella infection model,a survival rate of 70％was achieved with a preventative dose of 1 × 108 PFU/mL PJN025,compared to a 5％survival rate in the positive control group after 48 h of bacterial challenge.In SPF mice infected with S.typhimurium via intraperitoneal injection,all mices in the positive control group died within five days.However,in the co-infection group treated with 1×108 PFU/mL PJN025,a promising survival rate of 60％was observed.This study showed that the bacteriophage PJN025 had strong specificity,high lytic efficiency,good acid and alkali tol-erance,strong heat resistance,and good safety and prevention effects,providing materials and ex-perimental basis for the development of subsequent phage products.