ObjectiveTo investigate the role of Krüppel-like factor 4 （KLF4） in type 1 diabetic nephropathy （DN） and to elucidate its underlying mechanisms. MethodsSixteen male Sprague-Dawley （SD） rats were selected and randomly divided into control group and model group， with 8 rats in each group. Rats in model group were intraperitoneally injected with a single dose of 55 mg/kg streptozotocin （STZ） to establish a diabetic nephropathy （DN） model， while those in control group were injected with an equal volume of sodium citrate buffer at the same time. After successful model establishment， the serum levels of blood urea nitrogen （BUN） and serum creatinine （SCR） were determined. Hematoxylin-eosin （HE） staining was performed on renal tissues to observe pathological changes， and immunofluorescence staining was conducted to detect the expression of KLF4 in renal tissues. Lipid peroxidation levels were evaluated by measuring malondialdehyde （MDA）， Fe²⁺， and lipid peroxidation products in rat kidneys. A high glucose （HG）-induced cell injury model was established in HK-2 cells， with mitochondrial membrane potential assessed using 5，5'，6，6'-tetrachloro-1，1'，3，3'- tetraethylbenzimidazolylcarbocyanine iodide （JC-1） staining. Lipid peroxidation levels （MDA， Fe²⁺， and lipid peroxides） were measured in HK-2 cells.KLF4-overexpressing HK-2 cells were then constructed， followed by repeated JC-1， MDA， Fe²⁺， and lipid peroxidation assays. Western blot was performed to evaluate the expression of ferroptosis-related proteins including glutathione peroxidase 4 （GPX4）， nuclear factor erythroid 2-related factor 2 （NRF2）， and Kelch-like ECH-associated protein 1 （Keap1）， in renal tissues， HK-2 cells， and KLF4-overexpressing HK-2 cells. ResultsCompared with the control group， DN rats exhibited elevated serum BUN and SCR levels， glomerular hypertrophy， renal interstitial fibrosis， and decreased KLF4 expression. Additionally， MDA， Fe²⁺， and lipid peroxidation levels increased， indicating enhanced ferroptosis in renal tissues， accompanied by reduced GPX4 and NRF2 expression and elevated Keap1 levels. Similarly， HG-treated HK-2 cells showed decreased KLF4 expression， increased MDA， Fe²⁺ and lipid peroxidation， elevated ferroptosis， and dysregulated GPX4/NRF2/Keap1 expression. However， KLF4 overexpression reversed these alterations induced by high glucose treatment. ConclusionIn the renal tissues of type 1 diabetic rats， the expression of KLF4 decreases the level of ferroptosis increases， and KLF4 overexpression could alleviate HG-induced HK-2 cell injury.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objective By establishing a model to screen out patients with potentially large positional deviations based on their abdominal circumference,personalized solutions can be taken to address setup errors in these patients and ensure treatment efficacy.Methods A total of 81 patients treated at Tianjin People's Hospital from May 2021 to June 2023 were selected as the study subjects.The correlations between setup errors in the lateral,longitudinal,and vertical directions and abdominal circumference were analyzed.Subsequently,linear regression was performed for the direction with a significant correlation to abdominal circumference to establish a linear regression model.Finally,the 81 patients were divided into a normal setup group and an abnormal setup group with 0.7 cm as the critical value.A receiver operating characteristic(ROC)curve was plotted,and the maximum Youden index was calculated to determine the optimal cutoff value for identifying patients prone to abnormal setup.Results The correlation analysis of abdominal circumference and setup errors in various directions showed that the correlation coefficient between abdominal circumference and longitudinal direction positioning error was 0.406 2,and the correlation was statistically significant and positively correlated.The correlation coefficients for abdominal circumference and the lateral as well as longitudinal directions were-0.117 5 and-0.067 47,respectively,with P values greater than 0.05,indicating no statistical significance.A linear regression model was established for abdominal circumference and longitudinal direction,and the results showed an R2of 0.165,with a regression coefficient B of 0.008(t=3.951,P<0.01),indicating that the model was well constructed.ROC curve analysis showed an area under the curve of 0.715,with a 95%confidence interval of 0.57-0.86 and a maximum Youden index of 0.478.The corresponding optimal cutoff value was determined to be at 87 cm,with sensitivity at 0.875 and specificity at 0.603.Conclusion The abdominal circumference is significant to diagnose whether the longitudinal setup error is abnormal.Patients with an abdominal circumference greater than 87 cm are more likely to experience abnormal positioning during radiotherapy,which is reflected in the longitudinal setup errors being the largest.It is recommended to provide individualized target area margins for patients with an abdominal circumference greater than 87 cm,or perform daily cone-beam computed tomography to correct setup errors,thereby ensuring target coverage and treatment efficacy.

Objective:To analyze the incidence and spatiotemporal clustering of hepatitis B in China from 2006 to 2020 and provide reference for hepatitis B prevention and control.Methods:The incidence data of hepatitis B in 31 provinces (autonomous regions and municipalities) from 2006 to 2020 were collected from National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. The incidence trend analysis was conducted by using software Joinpoint 5.0.2, and the spatiotemporal scan analysis was performed by using software SaTScan 10.1.2.Results:From 2006 to 2020, a total of 1 049 546 cases of acute hepatitis B were reported in China. The average annual reported incidence rate was 5.17/100 000. The reported incidence rate showed a decreasing trend during this period. The incidence decreased from 3.00/100 000 to 0.41/100 000 in age group 0-14 years, from 14.15/100 000 to 3.44/100 000 in age group 15-34 years, and from 6.87/100 000 to 3.72/100 000 in age group ≥35 years, the differences were all significant (all P<0.001). From 2006 to 2020, a total of 10 732 017 cases of chronic hepatitis B were reported in China. The average annual reported incidence rate was 52.85/100 000. The reported incidence of chronic hepatitis B varied in different age groups, which decreased from 11.38/100 000 to 2.18/100 000 in age group 0-14 years, and from 73.17/100 000 to 61.40/100 000 in age group 15-34 years, while increased from 48.07/100 000 to 90.75/100 000 in age group ≥35 years, the differences were all significant (all P<0.05). Spatiotemporal scan analysis indicated that the age of reported acute hepatitis B cases became older over time, and the regions with high-incidence gradually shifted from western China to southwestern China. The overall reported incidence of chronic hepatitis B in those aged ≥35 years showed an upward trend, and the regions with high-incidence were mainly found in coastal area in southeastern China and in southwestern China. Conclusions:From 2006 to 2020, the overall reported incidence of acute hepatitis B in China showed a continuous downward trend, while the reported incidence of chronic hepatitis B in those aged ≥35 years showed an upward trend. It indicated that the need to improve the diagnosis and treatment of chronic hepatitis B in adults in coastal area in southeastern China and southwestern China.

Objective By establishing a model to screen out patients with potentially large positional deviations based on their abdominal circumference,personalized solutions can be taken to address setup errors in these patients and ensure treatment efficacy.Methods A total of 81 patients treated at Tianjin People's Hospital from May 2021 to June 2023 were selected as the study subjects.The correlations between setup errors in the lateral,longitudinal,and vertical directions and abdominal circumference were analyzed.Subsequently,linear regression was performed for the direction with a significant correlation to abdominal circumference to establish a linear regression model.Finally,the 81 patients were divided into a normal setup group and an abnormal setup group with 0.7 cm as the critical value.A receiver operating characteristic(ROC)curve was plotted,and the maximum Youden index was calculated to determine the optimal cutoff value for identifying patients prone to abnormal setup.Results The correlation analysis of abdominal circumference and setup errors in various directions showed that the correlation coefficient between abdominal circumference and longitudinal direction positioning error was 0.406 2,and the correlation was statistically significant and positively correlated.The correlation coefficients for abdominal circumference and the lateral as well as longitudinal directions were-0.117 5 and-0.067 47,respectively,with P values greater than 0.05,indicating no statistical significance.A linear regression model was established for abdominal circumference and longitudinal direction,and the results showed an R2of 0.165,with a regression coefficient B of 0.008(t=3.951,P<0.01),indicating that the model was well constructed.ROC curve analysis showed an area under the curve of 0.715,with a 95%confidence interval of 0.57-0.86 and a maximum Youden index of 0.478.The corresponding optimal cutoff value was determined to be at 87 cm,with sensitivity at 0.875 and specificity at 0.603.Conclusion The abdominal circumference is significant to diagnose whether the longitudinal setup error is abnormal.Patients with an abdominal circumference greater than 87 cm are more likely to experience abnormal positioning during radiotherapy,which is reflected in the longitudinal setup errors being the largest.It is recommended to provide individualized target area margins for patients with an abdominal circumference greater than 87 cm,or perform daily cone-beam computed tomography to correct setup errors,thereby ensuring target coverage and treatment efficacy.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

As activated hepatic stellate cells (aHSCs) play a central role in fibrogenesis, they have become key target cells for anti-fibrotic treatment. Nevertheless, the therapeutic efficiency is constrained by the exosomes they secrete, which are linked to energy metabolism and continuously stimulate the activation of neighboring quiescent hepatic stellate cells (qHSCs). Herein, an intercellular communication interference strategy is designed utilizing paeoniflorin (PF) loaded and hyaluronic acid (HA) coated copper-doped ZIF-8 (PF@HA-Cu/ZIF-8, PF@HCZ) to reduce energy-related exosome secretion from aHSCs, thus preserving neighboring qHSCs in a quiescent state. Simultaneously, the released copper and zinc ions disrupt key enzymes involved in glycolysis to reduce bioenergy synthesis in aHSCs, thereby promoting the reversion of aHSCs to a quiescent state and further decreasing exosome secretion. Therefore, PF@HCZ can effectively sustain both aHSCs and qHSCs in a metabolically dormant state to ultimately alleviate liver fibrosis. The study provides an enlightening strategy for interrupting exosome-mediated intercellular communication and remodeling the energy metabolic status of HSCs with boosted antifibrogenic activity.

Objective:To analyze the incidence and spatiotemporal clustering of hepatitis B in China from 2006 to 2020 and provide reference for hepatitis B prevention and control.Methods:The incidence data of hepatitis B in 31 provinces (autonomous regions and municipalities) from 2006 to 2020 were collected from National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. The incidence trend analysis was conducted by using software Joinpoint 5.0.2, and the spatiotemporal scan analysis was performed by using software SaTScan 10.1.2.Results:From 2006 to 2020, a total of 1 049 546 cases of acute hepatitis B were reported in China. The average annual reported incidence rate was 5.17/100 000. The reported incidence rate showed a decreasing trend during this period. The incidence decreased from 3.00/100 000 to 0.41/100 000 in age group 0-14 years, from 14.15/100 000 to 3.44/100 000 in age group 15-34 years, and from 6.87/100 000 to 3.72/100 000 in age group ≥35 years, the differences were all significant (all P<0.001). From 2006 to 2020, a total of 10 732 017 cases of chronic hepatitis B were reported in China. The average annual reported incidence rate was 52.85/100 000. The reported incidence of chronic hepatitis B varied in different age groups, which decreased from 11.38/100 000 to 2.18/100 000 in age group 0-14 years, and from 73.17/100 000 to 61.40/100 000 in age group 15-34 years, while increased from 48.07/100 000 to 90.75/100 000 in age group ≥35 years, the differences were all significant (all P<0.05). Spatiotemporal scan analysis indicated that the age of reported acute hepatitis B cases became older over time, and the regions with high-incidence gradually shifted from western China to southwestern China. The overall reported incidence of chronic hepatitis B in those aged ≥35 years showed an upward trend, and the regions with high-incidence were mainly found in coastal area in southeastern China and in southwestern China. Conclusions:From 2006 to 2020, the overall reported incidence of acute hepatitis B in China showed a continuous downward trend, while the reported incidence of chronic hepatitis B in those aged ≥35 years showed an upward trend. It indicated that the need to improve the diagnosis and treatment of chronic hepatitis B in adults in coastal area in southeastern China and southwestern China.

Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.