Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Although teniposide(VM26)is widely used in the treatment of lymphoma,its poor water sol-ubility,low bioavailability and systemic toxicities still limit its clinical application.Nano-delivery systems are effective in increasing the bioavailability and reducing the toxicity of VM26,but there is an urgent need to overcome the problem of its non-specific targeting.Therefore,in this paper,we designed and constructed a hyaluronic acid-modified teniposide-targeted nano-delivery system(VM26-TNDS),and characterised its drug encapsulation rate,particle size and zeta potential.We also investigated the effects of VM26-TNDS on B-cell lymphoma cells with different expression of CD44 receptor,in terms of cellular targeting,inhibitory effect of proliferation,and induction of apoptosis and necrosis.The results showed that the drug encapsulation efficiency of VM26-TNDS exceeded 85％,and its liquid formulation could be stably stored at 4 ℃ for more than 6 months without precipitation.Based on CD44 receptor expression,Granta-519(high expression),Raji(medium-low expression)and SU-DHL-4(almost no expression)were screened for cellular experiments.Compared with VM26-NDS,the targeted modification could effec-tively reduce the uptake of VM26-TNDS by RAW264.7 and increase the uptake of VM26-TNDS by CD44 receptor-expressing lymphoma cells.The inhibitory proliferative effect and apoptotic necrosis-inducing a-bility of VM26-TNDS were stronger than those of VM26-NDS for Granta-519 and Raji cells,whereas there was no significant difference in the inhibitory effect on proliferation and ability to induce apoptosis and necrosis between VM26-NDS and VM26-TNDS in SU-DHL-4 cells,reflecting the targeting advantage for VM26-TNDS,as expected.However,its toxic effect on B-cell lymphoma cells only reflected the targeting advantage at some concentrations(0.25 μmol/L and 0.5 μmol/L),which met the expectation.The a-bove results indicate that a teniposide-targeted nano-delivery system,VM26-TNDS,has been successfully prepared in this study.VM26-TNDS improves the delivery efficiency of VM26 by targeting human B-cell lymphoma cells expressing the CD44 receptor,thus killing human B-cell lymphoma cells more effectively and overcoming the problem of non-specific targeting in drug delivery to improve the therapeutic effect.Its biological therapeutic effects and mechanisms still need to be proved by more in vitro and in vivo ex-perimental evidence.

Objective To investigate the effects of gut microbiota regulation combined with exercise rehabilitation on non-motor symptoms and neurological function in Parkinson's disease patients.Methods A total of 154 Parkinson's disease patients admitted to our hospital from January 2022 to January 2024 were selected as the subjects of the study.Using a random number table,these 154 patients were evenly divided into a control group and a treatment group,with 77 patients in each group.Both groups received standard treatments,but the control group also underwent exercise rehabilitation therapy,while the treatment group received probiotic supplementation and exercise rehabilitation therapy.The effectiveness of the two groups was then compared.Results Following the 12 weeks,24 weeks therapeutic regimen,The treatment group showed significantly better outcomes(P<0.05).Clinically meaningful reductions were observed in Hoehn-Yahr staging,alongside decreased scores on standardized instruments assessing psychiatric symptoms HAMA,HAMD,SCOPA-AUT,UPDRS Ⅰ-IV and PDSS(P<0.05).Concurrently,the study group exhibited enhanced MMSE(P<0.05).Fecal microbiome analyses revealed a favorable ecological shift characterized by increased colonization of beneficial genera Bifidobacterium and Lactobacillus,with concomitant suppression of pathobionts Enterococcus and Enterobacteriaceae.Gait analysis revealed increased step length,speed,and frequency in the treatment group(P<0.05).Conclusion Patients with Parkinson's disease who received probiotics combined with exercise rehabilitation treatment could effectively improve non-motor symptoms and neurological function,while promoting the balance of intestinal flora,and reduce clinical symptoms.

The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit antican-cer activities in various tumors.However,its underlying mechanisms remain elusive.In this work,we explore the role of receptor-interacting protein 1(RIP 1)which plays a crucial role in the process of cell death,in metformin-induced anticancer activities in lung cancer.Metformin inhibits lung cancer cell pro-liferation in a dose-dependent manner and promotes apoptotic cell death,as evidenced by metformin-in-duced PARP and caspase cleavage.Furthermore,the pan-caspase inhibitor z-VAD-fmk reverses met-formin-induced cell death.Western blot and qPCR results suggest that metformin markedly downregulates RIP1 expression without affecting its mRNA and ubiquitination levels(0 vs 80 mmol/L,100％vs 20％,100％vs 15％).Additionally,co-immunoprecipitation and immunofluorescence results reveal that met-formin may suppress RIP1 expression in an Hsp70-dependent manner,as metformin promotes Hsp70 deg-radation,and Hsp70 endogenously interacts with RIP1.Subsequent CCK-8,flow cytometry,and West-ern blot analyses suggest that metformin decreases Hsp70/RIP1 expression through AMPK/PKA/GSK-3βaxis.Consistently,results from a subcutaneous transplant tumor model indicate that metformin retards tumor growth without affecting mouse body weight.Collectively,these data highlight the part of RIP1 in metformin-induced anticancer activities in lung cancer in vitro and in vivo,providing novel strategy for lung cancer administration.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit antican-cer activities in various tumors.However,its underlying mechanisms remain elusive.In this work,we explore the role of receptor-interacting protein 1(RIP 1)which plays a crucial role in the process of cell death,in metformin-induced anticancer activities in lung cancer.Metformin inhibits lung cancer cell pro-liferation in a dose-dependent manner and promotes apoptotic cell death,as evidenced by metformin-in-duced PARP and caspase cleavage.Furthermore,the pan-caspase inhibitor z-VAD-fmk reverses met-formin-induced cell death.Western blot and qPCR results suggest that metformin markedly downregulates RIP1 expression without affecting its mRNA and ubiquitination levels(0 vs 80 mmol/L,100％vs 20％,100％vs 15％).Additionally,co-immunoprecipitation and immunofluorescence results reveal that met-formin may suppress RIP1 expression in an Hsp70-dependent manner,as metformin promotes Hsp70 deg-radation,and Hsp70 endogenously interacts with RIP1.Subsequent CCK-8,flow cytometry,and West-ern blot analyses suggest that metformin decreases Hsp70/RIP1 expression through AMPK/PKA/GSK-3βaxis.Consistently,results from a subcutaneous transplant tumor model indicate that metformin retards tumor growth without affecting mouse body weight.Collectively,these data highlight the part of RIP1 in metformin-induced anticancer activities in lung cancer in vitro and in vivo,providing novel strategy for lung cancer administration.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective To investigate the effects of gut microbiota regulation combined with exercise rehabilitation on non-motor symptoms and neurological function in Parkinson's disease patients.Methods A total of 154 Parkinson's disease patients admitted to our hospital from January 2022 to January 2024 were selected as the subjects of the study.Using a random number table,these 154 patients were evenly divided into a control group and a treatment group,with 77 patients in each group.Both groups received standard treatments,but the control group also underwent exercise rehabilitation therapy,while the treatment group received probiotic supplementation and exercise rehabilitation therapy.The effectiveness of the two groups was then compared.Results Following the 12 weeks,24 weeks therapeutic regimen,The treatment group showed significantly better outcomes(P<0.05).Clinically meaningful reductions were observed in Hoehn-Yahr staging,alongside decreased scores on standardized instruments assessing psychiatric symptoms HAMA,HAMD,SCOPA-AUT,UPDRS Ⅰ-IV and PDSS(P<0.05).Concurrently,the study group exhibited enhanced MMSE(P<0.05).Fecal microbiome analyses revealed a favorable ecological shift characterized by increased colonization of beneficial genera Bifidobacterium and Lactobacillus,with concomitant suppression of pathobionts Enterococcus and Enterobacteriaceae.Gait analysis revealed increased step length,speed,and frequency in the treatment group(P<0.05).Conclusion Patients with Parkinson's disease who received probiotics combined with exercise rehabilitation treatment could effectively improve non-motor symptoms and neurological function,while promoting the balance of intestinal flora,and reduce clinical symptoms.