Objective:To investigate the influences of lupinol on the proliferation,apoptosis and invasion of cer-vical cancer cells by regulating autophagy mediated by phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway.Methods:The proliferation rate of human cervical cancer cell line HeLa cells treated with 0,10,25,50,70,90 μmol/L lupinol was determined,and the appropriate concentration of lupinol was screened out.HeLa cells cultured in vitro were randomly grouped into control group,low-dose lupinol group,high-dose lupinol group,740 Y-P group(PI3K activator),and high-dose lupinol+740 Y-P group.After group intervention with lupinol and 740 Y-P,MDC fluorescence staining was used to detect the forma-tion of autophagic vacuolation of HeLa cells in each group;western blot was used to detect the expression of au-tophagy and PI3K/AKT/mTOR pathway-related proteins in HeLa cells in each group.HeLa cells cultured in vitro were randomly grouped into control group,low-dose lupinol group,high-dose lupinol group,high-dose lupinol+rapamycin(Rapa),and high-dose lupinol+3-methyladenine(3-MA)group.After the intervention of high dose of lupinol,Rapa and 3-MA,the proliferation of HeLa cells in each group was detected by MTT assay and plate colony formation assay;flow cytometry was used to detect the apoptosis of HeLa cells in each group;transwell assay was used to detect the invasion of HeLa cells in each group;western blot was used to detect the expressions of proliferation,apoptosis and epithelial-mesenchymal transition-related proteins in HeLa cells in each group.Re-sults:Compared with the control group,the relative content of autophagic vacuoles,the protein expressions of Mi-crotubule-associated protein 1A/1 B-light chain 3(LC3)Ⅱ/LC3Ⅰ,and Beclin-1 in the low and high dose lupinol groups were all increased(P＜0.05),the phosphorylated PI3K(p-PI3K)/PI3K,phosphorylated AKT(p-AKT)/AKT,and phosphorylated mTOR(p-mTOR)/mTOR decreased(P＜0.05);the relative content of autophagic vac-uoles,the protein expressions of LC3Ⅱ/LC3Ⅰ,and Beclin-1 in the high-dose lupinol group were further increased compared with the low-dose lupinol group(P＜0.05),the p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR were further decreased(P＜0.05);the relative content of autophagic vacuoles,the protein expressions of LC3Ⅱ/LC3Ⅰ,and Beclin-1 in 740 Y-P group decreased compared with the control group(P＜0.05),the p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR increased(P＜0.05).Compared with the high-dose lupinol group,the relative content of autophagic vacuoles,the protein expressions of LC3Ⅱ/LC3Ⅰ,and Beclin-1 in the high-dose lupinol+740 Y-P group decreased(P＜0.05),the p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR increased(P＜0.05).Com-pared with the control group,the cell proliferation rate,colony formation rate,invasion number,and the protein ex-pressions of proliferating cell nuclear antigen(PCNA),B cell lymphoma 2(Bcl-2)and Vimentin in the low and high dose groups of lupinol were all decreased(P＜0.05),the apoptosis rate,and the protein expressions of Bcl-2 as-sociated x protein(Bax)and zonula occludens protein 1(ZO-1)were all increased(P＜0.05);compared with the low-dose lupinol group,the cell proliferation rate,colony formation rate,invasion number,and the protein expres-sions of PCNA,Bcl-2 and Vimentin in the high-dose lupinol group were further decreased(P＜0.05),the apopto-sis rate,and the protein expressions of Bax and ZO-1 were further increased(P＜0.05).Compared with the high-dose lupinol group,the cell proliferation rate,colony formation rate,invasion number,and the protein expres-sions of PCNA,Bcl-2 and Vimentin in the high-dose lupinol+Rapa group were increased(P＜0.05),the apopto-sis rate,and the protein expressions of Bax and ZO-1 were decreased(P＜0.05);the cell proliferation rate,colo-ny formation rate,invasion number,and the protein expressions of PCNA,Bcl-2 and Vimentin in the high-dose lu-pinol+3-MA group were decreased(P＜0.05),the apoptosis rate,and the protein expressions of Bax and ZO-1 were increased(P＜0.05).Conclusions:Lupinol induces protective autophagy by inhibiting the PI3K/AKT/mTOR pathway,thereby promoting the apoptosis of cervical cancer cells and inhibiting their proliferation and inva-sion.Activation of autophagy attenuates the effects of lupinol on the proliferation,apoptosis and invasion of cervi-cal cancer cells.

Objective:To explore the impacts of dexmedetomidine combined with dizosin on sciatic nerve-femoral nerve block and blood glucose in diabetes foot patients undergoing surgery.Methods:A total of 120 diabetes foot patients underwent surgery who were admitted to Second Hospital of Shanxi Medical University from Jul. 2020 to Aug. 2022 were selected as the research objects. The anesthesia method was sciatic nerve block-femoral nerve block, and were randomly grouped into the control group (60 cases) and the observation group (60 cases). The control group was treated with diazosin, while the observation group was treated with dexmedetomidine combined with diazosin. The effects of sciatic nerve block and femoral nerve block, and blood glucose level were compared between the two groups.Results:The VAS scores at T1, T2 and T3 in the two groups were obviously lower than those at T0, and the VAS scores in the observation group were obviously lower than those in the control group ( P<0.05). The onset time of motor nerve block and sensory nerve block in the observation group was obviously lower than that in the control group ( P<0.05). The maintenance time of motor nerve and sensory nerve in the observation group was obviously higher than that in the control group ( P<0.05). Compared with T0, systolic blood pressure, diastolic blood pressure and heart rate in T1, T2 and T3 time periods in the two groups were obviously lower, and the observation group were obviously lower than the control group ( P<0.05) ; The observation group had no significant difference compared with the control group in terms of the incidence of adverse reactions. Conclusion:Dexmedetomidine combined with dizosin can effectively relieve pain, improve nerve function block, and maintain the stability of hemodynamics in diabetes foot patients undergoing surgery.

Diabetic foot is one of the common chronic complications， the most common cause of hospitalization， and even the main cause of disability and death among diabetic patients. In the process of disease occurrence， development， and treatment， patients experience complex changes in physical， psychological， and social relationships. Their understanding and practice of the disease is a constant process of construction and change， which contains strategic practices influenced by factors such as disease progression， family relationships， culture and traditions of social， and doctor-patient interactions. Based on the research concepts in the field of medical anthropology， this paper applied field research methods such as survey interviews and participatory observation， and took the rich and varied and personalized narrative of diabetic foot patients as the entry point to understand their unique and detailed disease stories， as well as focused on answering the changes in the views of illness， treatment， family， society， and the body outlook experienced by diabetic foot patients. This paper aimed to provide a new perspective for understanding this group， as well as offer valuable insights for improving their treatment and management， which will help promote the overall health and quality of life with diabetic foot patients.

ObjectiveTo investigate the correlation between mild cognitive impairment (MCI) and traditional Chinese medicine (TCM) body constitution types in the elderly, and to provide an evidence for the control of cognitive impairment in the elderly. MethodsThe elderly aged 65 and above who participated in the community physical examinations in a community of Changning District, Shanghai were selected as the research subjects. The cognitive function was assessed by using the Clock Drawing Test combined with the Ascertain Dementia 8-item Questionnaire (AD8), the Montreal Cognitive Assessment (MoCA) and the Mini-mental State Examination (MMSE). The diagnostic criteria for MCI was identified based on the 2018 Chinese Guidelines for the Diagnosis and Treatment of Dementia and Cognitive Disorders, along with the assessment results and clinical history information. The current investigation method was used to collect the basic information and the prevalence of chronic disease of the subjects through questionnaire inquiries. The elderly subjects’ ability to take care of themselves was evaluated based on the Elderly Self⁃Care Ability Evaluation Scale, while the TCM body constitution types were determined based on the Chinese Medicine Health Care Management Service Specification. The association of the detection rate of MCI with gender, education level, history of chronic disease and TCM body constitution types were analyzed lastly. ResultsA total of 2 351 elderly people were investigated, including 1 037 males and 1 314 females, with an average age of (74.11±6.15) years. 174 subjects, accounting for 7.40%, were identified with MCI. The highest detection rate of MCI in the elderly are those with a Qi stagnation constitution (10.8%), followed by those with a dampness-heat constitution (9.1%) and a Qi deficiency constitution (8.4%). Multivariate logistic regression analysis showed that advanced age, lower educational level, a history of tuberculosis, and TCM constitutions such as dampness-heat, Qi stagnation, and Qi deficiency were the potential risk factors for MCI. ConclusionThere is a significant association between TCM constitution types such as dampness-heat, Qi stagnation, and Qi deficiency with MCI. TCM techniques can be integrated into the health management services for the elderly population, and targeted interventions can be provided to those with imbalanced constitution types so as to reduce the risk of MCI.

Based on the perspective of medical equipment safety culture,analyze the Global Patient Safety Report 2024 released by the World Health Organization(WHO)on May 30,and extract patient safety elements related to medical devices.Propose to initiate action plan for patient safety related to medical devices and discuss the pathway and measures to further ensure patient safety and strengthen safety management in the clinical use of medical devices,in conjunction with promoting high-quality development of hospitals.

A purified polysaccharide with a galactose backbone(SPR-1,Mw 3,622 Da)was isolated from processed Polygonati Rhizoma with black beans(PRWB)and characterized its chemical properties.The backbone of SPR-1 consisted of[(4)-β-D-Galp-(1]9→ 4,6)-β-D-Galp-(1 → 4)-α-D-GalpA-(1 → 4)-α-D-GalpA-(1 →4)-α-D-Glcp-(1 → 4,6)-α-D-Glcp-(1 → 4)-α/β-D-Glcp,with a branch chain of R1:β-D-Galp-(1 → 3)-β-D-Galp-(1 → connected to the →4,6)-β-D-Galp-(1 → via O-6,and a branch chain of R2:α-D-Glcp-(1 →6)-α-D-Glcp-(1 → connected to the →4,6)-α-D-Glcp-(1 → via O-6.Immunomodulatory assays showed that the SPR-1 significantly activated macrophages,and increased secretion of NO and cytokines(i.e.,IL-1β and TNF-α),as well as promoted the phagocytic activities of cells.Furthermore,isothermal titration calorimetry(ITC)analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant(KD)of 18.8 μM.It was suggested that SPR-1 activated the immune response through Toll-like receptor 4(TLR4)signaling and downstream responses.Our research demon-strated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response,and also provided an easily accessible way that can be used for PR deep processing.

Background/Aims: Hepatitis B virus (HBV)-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it to an HBV-related HCC patient (NCT05339321). Methods: Good Manufacturing Practice-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh class A, Barcelona Clinic Liver Cancer stage B, Eastern Cooperative Oncology Group performance status 0, hepatitis B e antigen-, serum hepatitis B surface antigen [HBsAg]+, HBsAg+ hepatocytes 10%) received 7.9×107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated. Results: SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-HCC cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1,404 U/L, and concurrently, serum HBsAg started decreasing by 3.84 log10 and remained <1 IU/mL for over six months. HBsAg-expressing hepatocytes in liver biopsies were undetectable after 73 days. The patient achieved a partial response according to modified RECIST with a >70% reduction in target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient’s blood. Conclusions SCG101 T-cell therapy showed encouraging efficacy and safety in preclinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.

Background: Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown. Methods: The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro. Results: ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis. Conclusion The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.

OBJECTIVE: To explore the clinical characteristics and genetic variants in a patient with adult ceroid lipofuscinosis neuronal type 7 (ACLN7). METHODS: A female patient diagnosed with ACLN7 in Henan Provincial People's Hospital in June 2021 was selected as the study subject. Clinical data, auxiliary examination and result of genetic testing were retrospectively analyzed. RESULTS: The patient, a 39-year-old female, has mainly presented progressive visual loss, epilepsy, cerebellar ataxia and mild cognitive decline. Neuroimaging analysis has revealed generalized brain atrophy, prominently cerebellum. Fundus photography has revealed retinitis pigmentosa. Ultrastructural skin examination has revealed granular lipofuscin deposits in the periglandular interstitial cells. Whole exome sequencing revealed that she has harbored compound heterozygous variants of the MSFD8 gene, namely c.1444C>T (p.R482*) and c.104G>A (p.R35Q). Among these, c.1444C>T (p.R482*) was a well established pathogenic variant, while c.104G>A (p.R35Q) was a missense variant unreported previously. Sanger sequencing confirmed that the daughter, son and elder brother of the proband have respectively carried heterozygous c.1444C>T (p.R482*), c.104G>A (p.R35Q), and c.104G>A (p.R35Q) variants of the same gene. The family has therefore fit with the autosomal recessive inheritance pattern of the CLN7. CONCLUSION Compared with previously reported cases, this patient has the latest onset of the disease with a non-lethal phenotype. Her clinical features have involved multiple systems. Cerebellar atrophy and fundus photography may be indicative of the diagnosis. The c.1444C>T (p.R482*) and c.104G>A (p.R35Q) compound heterozygous variants of the MFSD8 gene probably underlay the pathogenesis in this patient.
Male ; Female ; Humans ; Membrane Transport Proteins/genetics* ; Neuronal Ceroid-Lipofuscinoses/diagnosis* ; Retrospective Studies ; Atrophy ; Mutation

Objective To retrospectively evaluate the clinical efficacy and safety of brentuximab vedotin(BV) combined with chemotherapy in the treatment of malignant lymphoma. Methods We collected the data of 32 lymphoma patients with CD30-positive status, including 14 cases of Hodgkin's lymphomas, 2 cases of diffuse large B-cell lymphomas, and 16 cases of mature T/NK cell lymphomas. Chemotherapy combined with BV was administered to all patients for a minimum of two cycles. The efficacy of the treatment was evaluated according to Lugano criteria every two cycles. Results Complete response rate and overall response rate after four cycles of treatment were 22% and 50%, respectively. Sixteen cases (50.0%) had grades 1 and 2 toxicity, and 16 cases (50.0%) had grade 3 toxicity or higher. The most common adverse events were neutropenia (50.0%), pneumonia (46.9%), and anemia (43.8%). The most common grade 3 or higher adverse events were pneumonia (18.8%) and febrile neutropenia (12.5%). Four patients discontinued brentuximab vedotin because of severe adverse events. Conclusion BV is effective in treating relapsed and refractory CD30- positive Hodgkin's lymphoma and peripheral T-cell lymphoma, and its overall safety is acceptable.