OBJECTIVE: Since Omicron will likely persist, this trial evaluates the safety and efficacy of Shufeng Jiedu Granule (SFJDG) for mild Omicron infection, aims at finding new therapies especially for home-treated patients. METHODS: This randomized, double-blind, placebo-controlled, multi-center phase III trial involves 844 patients, divided into a treatment group (422) and control group (422). Participants will receive SFJDG or placebo for 7 d (1.2 g/bag, 2 bags, 3 times/d). Hospital evaluations will be done on days 1 and 8, with telephone assessments on days 3 and 5. Follow-up continues on days 10 and 14. Diary cards will track symptom scores and safety data. The primary outcome is the time to sustained clinical recovery from corona virus disease 2019 (COVID-19) symptoms. An interim analysis will occur after 70 % of patients complete follow-up, with Type I error correction (α1 = 0.015) at interim analysis based on O'Brien-Fleming-type cumulative error spending function. RESULTS: This phase III trial evaluates the efficacy and safety of SFJDG for mild COVID-19, focusing on real-world applicability for home-managed patients. The study's randomized, double-blind, placebo-controlled design ensures methodological rigor, while its comprehensive outcome measures address both symptom recovery and treatment safety. By emphasizing symptom resolution and recovery time, the trial aligns with the clinical priorities for managing mild cases of COVID-19. The findings could offer valuable insights into SFJDG's role in improving patient outcomes and addressing gaps left by existing antiviral therapies, particularly in symptom management. CONCLUSION The global risk assessment remains high due to the ongoing virulence of SARS-CoV-2 Omicron sub-lineages. This Phase III study adopts a robust methodology to investigate SFJDG as a treatment for mild COVID-19 as well as it's effectiveness and safety. Furthermore, this study aim to provide sufficient scientific evidence for the market registration of SFJDG especially for home-treated patients. If successful, SFJDG could be a meaningful addition to therapeutic options for mild infections, supporting public health strategies in managing the ongoing impact of SARS-CoV-2.

Background and purpose:Plasmacytoid dendritic cells are one of the key immune cells in the tumor microenvironment(TME),which can directly or indirectly regulate tumor related immune responses and play multiple roles in the development and metastasis of tumors.This study aimed to investigate the correlation between plasmacytoid dendritic cells in lymph nodes and lymph node metastasis in patients with advanced gastric cancer.Methods:Postoperative lymph node tissue specimens and clinicopathological data from advanced gastric cancer patients who underwent D2 radical surgery in the Department of General Surgery at the First Hospital of Dandong were gathered from January 2019 to December 2023.The lymph nodes were grouped based on pTNM staging and the diameter of metastatic lesions.This study was approved by the Medical Ethics Committee of Dandong First Hospital(No.DDSDYYY-LLSC-2025-02-18-019-01),and all patients signed informed consents.Immunohistochemical staining was used to detect the expression levels of CD123-positive plasmacytoid dendritic cells in different lymph node groups,and their correlation with lymph node metastasis in advanced gastric cancer was further analyzed.Results:Of the 116 patients,plasmacytoid dendritic cells infiltrate the lymph node tissues of gastric cancer patients.As tumor differentiation decreased and pT stage,pathological stage,lymphatic/vascular invasion,and perineural invasion increased,the mean number of CD123-positive pDC in metastatic lymph nodes rose significantly(P＜0.05).The number of CD123-positive plasmacytoid dendritic cells was higher in metastatic lymph node-positive tissues than in metastatic lymph node-negative tissues,the number was higher in the macrometastasis group of pN1-3 staging than in the micrometastasis group,and the number was higher in the non-metastatic lymph node group of pN1-3 staging than in the pN0 staging lymph node group(P＜0.05).In lymph node metastasis-positive cases,the number of CD123-positive plasmacytoid dendritic cells was higher in second-station lymph nodes than in first-station lymph nodes(P＜0.05).Conclusion:The infiltration of CD123-positive plasmacytoid dendritic cells in lymph nodes of patients with advanced gastric cancer is closely associated with lymph node metastasis and may serve as a prerequisite for metastatic spread.Understanding the distribution of CD123-positive plasmacytoid dendritic cells in gastric cancer lymph nodes can help further explore their role in the immune microenvironment of gastric cancer.Targeted therapy focusing on CD123-positive plasmacytoid dendritic cells may become a new strategy for the treatment of advanced gastric cancer.

Background and purpose:Plasmacytoid dendritic cells are one of the key immune cells in the tumor microenvironment(TME),which can directly or indirectly regulate tumor related immune responses and play multiple roles in the development and metastasis of tumors.This study aimed to investigate the correlation between plasmacytoid dendritic cells in lymph nodes and lymph node metastasis in patients with advanced gastric cancer.Methods:Postoperative lymph node tissue specimens and clinicopathological data from advanced gastric cancer patients who underwent D2 radical surgery in the Department of General Surgery at the First Hospital of Dandong were gathered from January 2019 to December 2023.The lymph nodes were grouped based on pTNM staging and the diameter of metastatic lesions.This study was approved by the Medical Ethics Committee of Dandong First Hospital(No.DDSDYYY-LLSC-2025-02-18-019-01),and all patients signed informed consents.Immunohistochemical staining was used to detect the expression levels of CD123-positive plasmacytoid dendritic cells in different lymph node groups,and their correlation with lymph node metastasis in advanced gastric cancer was further analyzed.Results:Of the 116 patients,plasmacytoid dendritic cells infiltrate the lymph node tissues of gastric cancer patients.As tumor differentiation decreased and pT stage,pathological stage,lymphatic/vascular invasion,and perineural invasion increased,the mean number of CD123-positive pDC in metastatic lymph nodes rose significantly(P＜0.05).The number of CD123-positive plasmacytoid dendritic cells was higher in metastatic lymph node-positive tissues than in metastatic lymph node-negative tissues,the number was higher in the macrometastasis group of pN1-3 staging than in the micrometastasis group,and the number was higher in the non-metastatic lymph node group of pN1-3 staging than in the pN0 staging lymph node group(P＜0.05).In lymph node metastasis-positive cases,the number of CD123-positive plasmacytoid dendritic cells was higher in second-station lymph nodes than in first-station lymph nodes(P＜0.05).Conclusion:The infiltration of CD123-positive plasmacytoid dendritic cells in lymph nodes of patients with advanced gastric cancer is closely associated with lymph node metastasis and may serve as a prerequisite for metastatic spread.Understanding the distribution of CD123-positive plasmacytoid dendritic cells in gastric cancer lymph nodes can help further explore their role in the immune microenvironment of gastric cancer.Targeted therapy focusing on CD123-positive plasmacytoid dendritic cells may become a new strategy for the treatment of advanced gastric cancer.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

【Objective】 To investigate the practice and benefit of national standardized management of type 2 diabetes in Yulin City. 【Methods】 We recruited the adult type 2 diabetes patients who sought medical help at our hospital from May 2020 to October 2022 as subjects. We collected their basic information (sex and age); measured height, weight, waist and hip circumference, and blood pressure; calculated body mass index (BMI); and detected blood glucose, c-peptide, HbA1c, biomarkers, urinary microalbumin, sensory nerve conduction velocity of lower limbs, ABI, and subcutaneous and visceral fat at the time of MMC recruited and the end of six months. T test and Mann-Whitney U rank sum test were used for measurement data and χ² test or Fisher’s exact probability method for counting data to analyze the data. 【Results】 After 6 months, the levels of fasting blood glucose, postprandial blood glucose, HbA1c, and visceral and subcutaneous fat in all the patients decreased, but the level of fasting c-peptide increased compared with the baseline (all P<0.05). Secondly, compared with the baseline, the control rate of HbA1c (35.21% vs. 13.71% ) and the comprehensive control rate (13.97% vs. 7.26% ) were both significantly increased at six months (P<0.05). Thirdly, after 6 months, the levels of fasting blood glucose, postprandial blood glucose, HbA1c, TG, TC, and UA were decreased more, while the fasting c-peptide and postprandial c-peptide were increased more in the patients of the HbA1c standard group (HbA1c<7% ) than those of the non-standard group. 【Conclusion】 The multiple benefits of blood glucose, blood lipid, uric acid and islet function can be achieved by taking type 2 diabetes patients into MMC. Meanwhile, the rates of HbA1c control and comprehensively reaching the standard are significantly increased. Therefore, MMC can explore a new way for the management of type 2 diabetic patients in this area.

Objective:To investigate the mechanism underlying the inhibiting effect of low-glucose combined with palmitic acid on human colon cancer cells and its influence on the radiosensitivity.Methods:Under the treatment of low-glucose, palmitic acid and low-glucose combined with palmitic acid, the treatment condition that significantly inhibited the proliferation of SW480 was screened by CCK-8 assay. The reactive oxygen species (ROS) level, mitochondrial membrane potential and apoptosis rate were detected by flow cytometry. The changes in the radiosensitivity were detected by immunofluorescence-based γ-H 2AX quantification and colony formation assay. The protein expression level was detected by Western blot. Results:Compared with the control group, the condition of low-glucose combined with 120μmol/L palmitic acid significantly inhibited the proliferation of SW480 cells ( P<0.01). The expression levels of CPT1a, PFKFB3 and PKM were significantly up-regulated, the expression levels of NDUFV1, NDUFV2 and NDUFS1 were remarkably down-regulated, the ROS level was significantly increased and the ATP level was considerably reduced in the cells under metabolic stress (all P<0.01). After irradiation, the number of γ-H 2AX foci was significantly increased ( P<0.05), and the D 0 value was significantly reduced ( P<0.01), the ROS level was considerably increased ( P<0.001), the apoptosis rate was significantly increased ( P<0.001) and the expression level of γ-H 2AX protein was remarkably up-regulated ( P<0.01) in the low-glucose combined with 120μmol/L palmitic acid group. Pretreatment with NAC could reverse the changes of ROS, apoptosis and γ-H 2AX protein expression. Conclusions:The combination of low-glucose and palmitic acid can induce metabolic stress in SW480 cells, inhibit tumor proliferation and increase the radiosensitization when combined with radiotherapy by inducing the generation of ROS and DNA damage.

Objective:To observe the effect of recuperation pathway based interventions on uric acid and lipid of sea diving personnel in a naval recuperation center.Methods:A total of 1 149 cases of sea diving personnel admitted to a Recuperation Center for PLA Naval Special Duty Personnel from July 2015 to December 2020 were studied. After admission, their blood samples were taken for testing uric acid and lipid. Those with abnormal levels of uric acid and lipid were given the interventions based on recuperation pathway, and their levels of uric acid and lipid were re-examined 15 days after the intervention.Results:After intervention, the levels of uric acid, total cholesterol, triglyceride, and low-density lipoprotein were lower than those before intervention, and the differences were statistically significant ( P<0.05). Conclusion:The recuperation pathway based intervention plan adopted by the center can effectively reduce the uric acid and lipid levels of sea diving personnel. With reasonable recuperation plans, better improvement in the health of sea diving personnel can be achieved.

Objective:To observe the effect of recuperation pathway based interventions on uric acid and lipid of sea diving personnel in a naval recuperation center.Methods:A total of 1 149 cases of sea diving personnel admitted to a Recuperation Center for PLA Naval Special Duty Personnel from July 2015 to December 2020 were studied. After admission, their blood samples were taken for testing uric acid and lipid. Those with abnormal levels of uric acid and lipid were given the interventions based on recuperation pathway, and their levels of uric acid and lipid were re-examined 15 days after the intervention.Results:After intervention, the levels of uric acid, total cholesterol, triglyceride, and low-density lipoprotein were lower than those before intervention, and the differences were statistically significant ( P<0.05). Conclusion:The recuperation pathway based intervention plan adopted by the center can effectively reduce the uric acid and lipid levels of sea diving personnel. With reasonable recuperation plans, better improvement in the health of sea diving personnel can be achieved.

Objective:To investigate the expression of Pyruvate dehydrogenase kinase 1(PDK1), phosphorylated Pyruvate dehydrogenase (p-PDH) and Pyruvate kinase isozyme type M2 (PKM2) based on Warburg effect pathway in cervical cancer tissues, and explore the roles of these molecules on prognosis and recurrence after postoperative radiation.Methods:The expressions of PDK1, p-PDH and PKM2 in primary tissues of 102 patients with cervical cancer were detected by immunohistochemistry, including 63 patients receiving postoperative radiation. The expression of the three molecules on prognosis and the efficacy of postoperative radiation on cervical cancer were analyzed separately and corporately.The level of mRNA were verified by using the 300 patients from GEO database. Kaplan-Meier method and COX proportional hazards regression model were used for univariate and multivariate analysis.Results:High expression of PDK1 and all the three indicators (PDK1 high/p-PDH high/PKM2 high) were positively correlated with pelvic lymphnode metastasis ( χ2=10.890, 7.407, P<0.05). PDK1 high/p-PDH high/PKM2 high, Federation International of Gynecology and Obstetrics (FIGO) staging, pelvic lymph node metastasis and postoperative radiation could affect the overall survival (OS) and disease-free survival (DFS) ( P<0.05). Multivariate analysis showed that PDK1 high /PDH high/PKM2 high, FIGO staging and postoperative radiation were the independent prognosis factors for OS and DFS( P<0.05). The verification result of the GEO dataset showed that PDK1 high/PDH high/PKM2 high was the risk factor for DFS( P<0.05). Pathological type, pelvic lymph node metastasis and PDK1 high/p-PDH high/PKM2 high could affect the DFS of those patients with postoperative radiation ( P<0.05). In addition, the multivariate analysis showed that pathological type and PDK1 high /p-PDH high/PKM2 high were the independent prognosis factors for DFS( P<0.05). Conclusions:The patients of PDK1 high /p-PDH high/PKM2 high phenotype have poor prognosis and DFS with postoperative radiation, which may be a high-risk group with poor prognosis and high recurrence rate after postoperative radiotherapy of stageⅠ-Ⅱ B cervical cancer.This study provides a novel strategy for stratified treatment of cervical cancer.