Aging is a natural process in which tissue and organ function declines as organisms age. Aging is the inevitable outcome of the organism and is irreversible. The aging process is accompanied by degenerative changes in the morphological structure of multiple organs of the body, leading to an increase in the incidence of chronic diseases such as hypertension, cardiovascular and cerebrovascular diseases, hyperlipidemia, and diabetes year by year. In recent years, natural phytochemicals have attracted widespread attention from the public due to their advantages such as non-toxicity or low toxicity, low cost, and various biological activities. Epigallocatechin gallate (EGCG) is a dietary polyphenol extracted from green tea, which has a variety of biological functions including anti-oxidation, anti-inflammation, hypoglycemic, hypolipidemic and anti-aging activities. The EGCG-mediated anti-aging mechanism has been investigated in many studies with different aging models. This article reviews the research progress on rodents, nematodes, fruit flies, and cell aging models, focusing on summarizing the lifespan extension and physiological changes of rodents, nematodes and fruit flies after EGCG intervention from multiple angles, and exploring potential mechanism by which EGCG delays aging and extends lifespan. This review provides a theoretical reference for the study of the anti-aging mechanism of phytochemicals.

Objective To investigate the effects and mechanisms of Tiaoqi Zhike Prescription(Ephedrae Herba,Armeniacae Semen Amarum,Fritillariae Thunbergii Bulbus,Scutellariae Radix,Trichosanthis Semen,etc.)on airway inflammation in cough variant asthma rats based on the MAPK/NF-κB signaling pathway.Methods Cough variant asthma rat model was established by ovalbumin sensitization.SD rats were randomly divided into blank group,model group,Dexamethasone group(0.5 mg·kg-1),Montelukast group(1.0 mg·kg-1)and Tiaoqi Zhike Prescription low-,medium-and high-dose groups(9.6,19.2,38.4 g·kg-1),with 10 rats in each group.Intragastric administration was given once a day for 14 consecutive days.The general condition of rats was observed and the number of coughs in rats within two minutes after atomization was recorded.HE staining and Masson staining were used to observe the pathological changes of lung tissue in rats.The levels of serum interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)were detected by ELISA.The protein expression levels of p38 MAPK,p-p38,NF-κB p65 and p-p65 in lung tissue were detected by Western Blot.The mRNA expression levels of p38 MAPK and NF-κB p65 in lung tissue were detected by RT-qPCR.Results Compared with the blank group,the times of coughs in the model group was significantly increased(P＜0.01),and the pathological score of lung injury and the area ratio of collagen fibers were significantly increased(P＜0.01).The levels of serum IL-1β,IL-6 and TNF-α were significantly increased(P＜0.01).The protein expressions of p-p38,p-p65,p-p38/p38 and p-p65/p65 in lung tissue were significantly up-regulated(P＜0.01),and the mRNA expressions of p38 MAPK and NF-κB p65 were significantly up-regulated(P＜0.01).Compared with the model group,the cough frequency of rats in each administration group was significantly decreased(P＜0.01),the pathological score of lung injury and the area ratio of collagen fibers were significantly decreased(P＜0.01),the levels of serum IL-1β,IL-6 and TNF-α were significantly decreased(P＜0.01),and the protein expressions of p-p38 and p-p65 and the mRNA expressions of p38 MAPK and NF-κB p65 in lung tissue were significantly down-regulated(P＜0.05,P＜0.01).The protein expression ratios of p-p3/p38 and p-p65/p65 in the lung tissue of rats in the high-dose group of Tiaoqi Zhike Prescription were significantly down-regulated(P＜0.01).Compared with the Dexamethasone group and the Montelukast group,the number of coughs in the high-dose group of Tiaoqi Zhike Prescription was significantly reduced(P＜0.05).Compared with the Dexamethasone group,the serum levels of IL-1β,IL-6 and TNF-α in the high-dose group of Tiaoqi Zhike Prescription were significantly decreased(P＜0.01).Compared with the Montelukast group,the levels of serum IL-1β and TNF-α in the high-dose group of Tiaoqi Zhike Prescription were significantly decreased(P＜0.05,P＜0.01).Conclusion Tiaoqi Zhike Prescription can improve the cough symptoms of ovalbumin-induced cough variant asthma model rats,reduce airway inflammatory cell infiltration and airway remodeling,and reduce the levels of inflammatory cytokines IL-1β,IL-6 and TNF-α.The mechanism may be related to the regulation of MAPK/NF-κB signaling pathway.

Objective To validate the mechanism of Mori Cortex-Lycii Cortex(MCLC)in intervening acute lung injury(ALI)based on network pharmacology,molecular docking combined with animal experiments.Methods The TCMSP database was used to obtain the active components of MCLC;the SwissTargetPrediction database was used to predict the targets of active components;the GeneCards database and DisGeNET database were used to collect the disease targets of ALI;the key targets were screened by constructing a PPI network,and the key targets were subjected to GO and KEGG pathway enrichment;a drug-component-target-pathway network was constructed using Cytoscape software;AutoDock and PyMOL software were used to validate the molecular docking of some of the compounds and targets;LPS was used to establish a mouse model of ALI for experimental validation,and experimental validation was performed to main targets and pathways.Results Totally 44 active components of MCLC and 138 action targets were obtained;26 potential targets of MCLC intervention in ALI were obtained,mainly TNF,EGFR,NFKB1,MPO,TNFRSF1A,NOX4,etc.,and the key pathways were MAPK signaling pathway,IL-17 signaling pathway,NF-κB signaling pathway,etc.;molecular docking results showed that the core active components of MCLC and the main targets had strong binding activities;animal experiments showed that MCLC at medium and high dosages could effectively improve the lung histopathological damage in ALI mice,decrease the contents of IL-6 and TNF-α in serum(P<0.01),and increase IL-10 content(P<0.01);MCLC inhibited protein expressions of EGFR,PI3K,AKT,NF-κB p65 in lung tissue(P<0.01).Conclusion MCLC may intervene ALI by components such as quercetin and buddleoside,acting on targets including EGFR and TNF,through ulti-pathways of EGFR/PI3K/NF-κB signaling pathway,etc.

Objective To analyze the correlation between serum miR-939 and miR-15b expression and mi-crovascular injury in patients with diabetic retinopathy(DR).Methods A total of 176 patients with type 2 di-abetes diagnosed and treated in the Baoding Second Hospital from January 2021 to October 2022 were selected as the study objects.The subjects were divided into 74 patients without DR(NDR group),62 patients with non-proliferative DR(NPDR group)and 40 patients with proliferative DR(PDR group)according to whether or not DR occurred and the degree of lesions.Real-time fluorescent quantitative PCR was used to detect the relative expression levels of miR-939 and miR-15b in serum of all groups,the level of vascular endothelial growth factor(VEGF)was detected by enzyme-linked immunosorbent assay,and the count percentage of en-dothelial cells(ECs),endothelial progenitor cells(EPCs)and circulating progenitor cells(CPCs)was detected by flow cytometry.Serum levels of miR-939,miR-15b,VEGF and ECs,EPCs and CPCs were compared in 3 groups.Pearson correlation was used to analyze the correlation between serum miR-939 and miR-15b and VEGF,ECs,EPCs and CPCs.Multivariate Logistic regression was used to analyze the factors affecting the oc-currence of DR in patients with type 2 diabetes.Results The relative expression levels of miR-939 and miR-15b in PDR group and NPDR group were lower than those in NDR group,while the serum VEGF levels were higher than those in NDR group,with statistical significance(P＜0.05).ECs in PDR group and NPDR group were higher than those in NDR group,while EPCs and CPCs were lower than those in NDR group,the differ-ence was statistically significant(P＜0.05).Serum miR-939 was negatively correlated with VEGF and ECs(r=-0.407,-0.613,P＜0.05),and positively correlated with EPCs and CPCs(r=0.481,0.486,P＜0.05).Serum miR-15b was negatively correlated with VEGF and ECs(r=-0.539,-0.625,P＜0.05),and positively correlated with EPCs and CPCs(r=0.451,0.483,P＜0.05).Multivariate Logistic regression anal-ysis showed that the duration of type 2 diabetes,hemoglobin A1c,2-hour postprandial blood glucose,VEGF,miR-939 and miR-15b were the influencing factors for the occurrence of DR in type 2 diabetes patients(P＜0.05).Conclusion The expression of miR-939 and miR-15b in serum of DR patients is closely related to VEGF,ECs,EPCs and CPCs,and the expression of miR-939 and miR-15b in serum of DR patients can provide a certain reference for early judgment and evaluation of the degree of microvascular injury.

Cinnamomi Ramulus and Alismatis Rhizoma are commonly used in the treatment of external-contraction diseases. Cinnamomi Ramulus is pungent， sweet， and warm， with the effects of ventilating lung and dispersing cold， warming Yang and transforming Qi， and promoting water and liquid flow from Taiyang meridian to remove dampness. Alismatis Rhizoma is sweet and cold， with the effects of draining dampness and promoting urination， regulating the waterway， removing water retention in lung， and promoting urination to remove dampness and heat. Herbal pairs are extracted from the accumulated experience of medical practitioners over the ages in the use of medicines and have been proved by clinical application to be composed of simple and effective combinations for specific diseases. The herb pair Cinnamomi Ramulus-Alismatis Rhizoma is an important part in ancient classic formulas such as Wulingsan. Both herbs play a role in draining dampness and promoting urination， warming Yang and transforming Qi， being a representative herb pair used for treating external-contraction exterior syndrome and water retention inside. The review of ancient medical publications revealed that there were a large number of compound formulas containing Cinnamomi Ramulus-Alismatis Rhizoma for dispersing cold and removing dampness， which were widely used for thousands of years in clinical practice. Modern pharmacological studies have shown that the active pharmacological components of Cinnamomi Ramulus （cinnamaldehyde and cinnamic acid） and Alismatis Rhizoma （alisol A and 23-acetate alisol B） have anti-inflammatory， antiviral， and immunoregulatory effects and high safety. Qingfei Paidu decoction containing this herbal pair played an important role in fighting against COVID-19. Despite the extensive pharmacological studies on Cinnamomi Ramulus and Alismatis Rhizoma， few studies have been carried out regarding this herb pair. This paper summarizes the traditional Chinese medicine knowledge about Cinnamomi Ramulus and Alismatis Rhizoma in the treatment of external-contraction diseases and summarizes the chemical composition， pharmacological effects， toxicology and other aspects of the two herbs before and after compatibility， aiming to provide a reference for further research and clinical application.

Objective To explore the association between visceral adiposity index(VAI)and nonalcoholic fatty liver disease(NAFLD)in lean population and the predictive value of VAI.Methods A total of 2 576 healthy subjects,body mass index(BMI)＜24 kg/m2,from The Second Affiliated Hospital of Xi'an Jiaotong University from June 2020 to May 2021 were randomly included and divided into lean NAFLD(n=213)and healthy control group(n=2 363).According to the VAI quartiles,they were divided into Q1-Q4 groups from low to high.The differences in biochemical parameters and the prevalence of NAFLD were compared among groups.The correlation between VAI and lean NAFLD was analyzed with restricted cubic spline(RCS),and the predictive value of VAI was explored by Logistic regression and receiver operating characteristic(ROC)curve.Results A total of 2 576 participants were included,and the prevalence of lean NAFLD was 8.3％(213 cases).The mean age,male ratio,BMI and waist circumference(WC)from group Q1 to group Q4 were significantly increased in a dose-response relationship(all P＜0.001).Compared with those in group Q1,systolic blood pressure,diastolic blood pressure,white blood cell count,hemoglobin concentration,alanine aminotransferase,aspartate aminotransferase,γ-glutamyl transpeptidase,alkaline phosphatase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,blood uric acid,and fasting blood glucose levels in groups Q2 to Q4 were significantly increased,while direct bilirubin and high-density lipoprotein cholesterol levels were gradually decreased(both P＜0.001).The prevalence rate of NAFLD in groups Q1-Q4 was 0.6％,3.3％,7.0％and 22.2％,respectively(P＜0.001).RCS showed that the risk of NAFLD in lean population rose significantly with the increase of VAI(P＜0.001),and there was a nonlinear relationship between them(P for nonlinear＜0.001).Logistic regression showed that after adjusting other confounding factors,the risk of lean NAFLD in groups Q2,Q3 and Q4 was still 2.926 times(95％CI:0.971-8.811),3.435 times(95％CI:1.154-10.230),and 5.920 times(95％CI:1.873-18.719)that Q1 group.ROC curve showed that VAI had a good predictive value for lean NAFLD,with area under the curve of 0.815,critical value of 1.532,diagnostic sensitivity of 77.9％and specificity of 72.8％,which were better than BMI and WC.Conclusion VAI is significantly associated with the risk of NAFLD in lean population,and thus has a good predictive value.It can be used for early screening and diagnosis of lean NAFLD.

Objective:The aim of this study was to evaluate the impact of neoadjuvant radiotherapy on anorectal function of patients with mid-low rectal cancer by means of high-resolution anorectal manometry.Methods:A retrospective observational study was conducted. Information on patients with mid-low rectal cancer was collected from the prospective registry database of Rectal Cancer at Peking Union Medical College Hospital (PUMCH) from June 2020 to April 2023. Anorectal functions were detected using three-dimensional high-resolution manometry system. Logistic regression analysis was performed to identify the factors associated with the changed anorectal manometry.Results:A total of 45 patients with mid-low rectal cancer were included in the study. Thirty-two (71.1%) patients were male, 13 (28.9%) patients were female. The mean age was 60±11 years, and the mean BMI was 23.4±3.7 kg/m 2. The mean distance between the lower edge of the tumor and the anal verge was 5.4±1.5 cm. The median size of the tumor was 3.4 (2.9-4.5) cm, and the median circumferential extent of the tumor was 66.0 (45.5-75.0) %. 41 (81.1%) patients were MRI T3-4 and 40 (88.9%) patients were MRI N positive. The resting pressure has a decreasing trend after neoadjuvant radiotherapy (55.3±32.0 mmHg vs. 48.0±28.5 mmHg, t=1.930, P=0.060). There was no significant change in maximum squeezing and the length of the high-pressure zone after neoadjuvant radiotherapy. All volumes describing rectal sensitivity (first sensation, desire to defecate, and maximum tolerance) were lower after neoadjuvant radiotherapy. And maximum tolerance was significantly lower (66.0 [49.0,88.0] ml vs. 52.0 [39.0,73.5] ml, Z=-2.481, P=0.013). Univariate analysis demonstrated that the downstage of N-stage was associated with the decrease in maximum tolerance (OR=6.533, 95%CI:1.254-34.051, P=0.026). Conclusion:Neoadjuvant radiotherapy damages anorectal function by decreasing the resting pressure and rectal sensory threshold of patients. The N-stage downstaging was associated with a decrease in maximum tolerance.

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.

Objective:The aim of this study was to evaluate the impact of neoadjuvant radiotherapy on anorectal function of patients with mid-low rectal cancer by means of high-resolution anorectal manometry.Methods:A retrospective observational study was conducted. Information on patients with mid-low rectal cancer was collected from the prospective registry database of Rectal Cancer at Peking Union Medical College Hospital (PUMCH) from June 2020 to April 2023. Anorectal functions were detected using three-dimensional high-resolution manometry system. Logistic regression analysis was performed to identify the factors associated with the changed anorectal manometry.Results:A total of 45 patients with mid-low rectal cancer were included in the study. Thirty-two (71.1%) patients were male, 13 (28.9%) patients were female. The mean age was 60±11 years, and the mean BMI was 23.4±3.7 kg/m 2. The mean distance between the lower edge of the tumor and the anal verge was 5.4±1.5 cm. The median size of the tumor was 3.4 (2.9-4.5) cm, and the median circumferential extent of the tumor was 66.0 (45.5-75.0) %. 41 (81.1%) patients were MRI T3-4 and 40 (88.9%) patients were MRI N positive. The resting pressure has a decreasing trend after neoadjuvant radiotherapy (55.3±32.0 mmHg vs. 48.0±28.5 mmHg, t=1.930, P=0.060). There was no significant change in maximum squeezing and the length of the high-pressure zone after neoadjuvant radiotherapy. All volumes describing rectal sensitivity (first sensation, desire to defecate, and maximum tolerance) were lower after neoadjuvant radiotherapy. And maximum tolerance was significantly lower (66.0 [49.0,88.0] ml vs. 52.0 [39.0,73.5] ml, Z=-2.481, P=0.013). Univariate analysis demonstrated that the downstage of N-stage was associated with the decrease in maximum tolerance (OR=6.533, 95%CI:1.254-34.051, P=0.026). Conclusion:Neoadjuvant radiotherapy damages anorectal function by decreasing the resting pressure and rectal sensory threshold of patients. The N-stage downstaging was associated with a decrease in maximum tolerance.

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.