ObjectiveTo investigate the potential active ingredients and targets of Baihu Jia Renshentang（BHJRST） for the treatment of obesity combined with type 2 diabetes mellitus（T2DM） by network pharmacology and in vivo experiments. MethodUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify the material basis of BHJRST. Subsequently， potential targets for the action of the active ingredients were queried in databases such as ChEMBL， Therapeutic Target Database（TTD）， YaTCM， DisGeNET and Traditional Chinese Medicine on Immuno-Oncology（TCMIO）， and the shared targets were identified by taking the intersection of these targets with disease targets. The shared targets were imported into the STRING database to construct a protein-protein interaction（PPI） network， the hub genes were identified by cytoHubba plug-in， and molecular docking was used to validate the binding energy of the hub genes to the bioactive ingredients in BHJRST. Meanwhile， the shared targets were imported into the DAVID platform for gene ontology（GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis. The predicted results were subsequently verified by animal experiments. Eighteen 8-week-old male skeletal muscle insulin-like growth factor-1 receptor dysfunction（MKR） mice were induced by a high-fat diet for 12 weeks in order to prepare a mouse model of obesity combined with T2DM. The mice were randomly divided into the model group， metformin group（0.2 g·kg^-1） and BHJRST group（27 g·kg^-1 in raw material）， and another 6 male FVB mice of the same age as the normal group. The mice in each group were were given the corresponding drugs by gavage， and the normal and model groups were given the same amount of distilled water by gavage， 1 time/d for 6 consecutive weeks. At the end of administration， the body mass， Lee's index， fasting blood glucose（FBG）， oral glucose tolerance test（OGTT） of mice in each group were examined， and the pathological morphology of the white adipose tissue of the epididymis was observed， and the expression of the mRNA of the hub genes in the white adipose tissue of the epididymis was detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultA total of 200 bioactive components of BHJRST were identified， of which 64 bioactive components were reverse-matched to 384 targets， and a total of 308 targets were associated with obesity combined with T2DM. Hub genes included mitogen-activated protein kinase 1（MAPK1）， signal transducer and activator of transcription 3（STAT3）， MAPK3， interleukin（IL）-2， Janus kinase 1（JAK1）， nuclear transcription factor-κB p65（RELA）， estrogen receptor 1（ESR1）， transcription factor AP-1（JUN）， MAPK14 and lymphocyte-specific protein tyrosine kinase（LCK）. GO functional annotation showed that it was mainly enriched in cytoplasm， cell membrane and nucleus， and was closely related to important biological processes such as peptide serine phosphorylation， protein phosphorylation and inflammation. In KEGG enrichment analysis， metabolic pathway， lipid and atherosclerosis， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） and MAPK signal pathways were significantly enriched. The molecular docking results showed that the hub genes had a stable binding relationship with 10 bioactive components， including quercetin， isoliquiritigenin， and morin， in BHJRST. The results of animal experiments showed that BHJRST could significantly reduce body mass， Lee's index and FBG levels（P<0.01） in mice with obesity combined with T2DM， improve the pathological changes of white adipose tissue， and down-regulate the the mRNA expression of the hub genes in white adipose tissue of the epididymis（P<0.01）. ConclusionIn this study， 10 potentially active components such as quercetin， isoliquiritigenin， and morin in BHJRST are identified through network pharmacology and animal experiments， and it is possible to treat obesity combined with T2DM by regulating lipid and atherosclerosis， phosphatidylinositol PI3K/Akt and MAPK signal pathways， which provides important clues and theoretical basis for the study of its mechanism and clinical application.

Toxoplasma gondii(T.gondii or Tg),is an obligatory intracellular parasite with humans as its intermediate hosts.In recent years,significant correlations between T.gondii infection and schizophrenia have been reported,including the possible mediating mechanisms.Currently,mechanisms and hypotheses focus on central neurotransmitters,immunity,neuroinflammation,and epigenetics;however,the exact underlying mechanisms remain unclear.In this article,we review the studies related to T.gondii infection and schizophrenia,particularly the latest research progress.Research on dopamine(DA)and other neurotransmitters,the blood-brain barrier,inflammatory factors,disease heterogeneity,and other confounders is also discussed.In addition,we also summarized the results of some new epidemiological investigations.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

Objective To conduct basic research on the structure and function of the heart in cynomolgus monkeys older than 10 years to provide data for animal selection in elderly disease research.Methods A total of 144 cynomolgus monkeys＞10 years old were selected as research subjects,including 37 females and 66 males in the 10～15 years group,and 21 females and 20 males in the 16～20 years group.Basic data on cardiac structure and function in middle-aged and elderly cynomolgus monkeys were obtained through comparative analysis of general indicators(body mass index,blood pressure,and heart rate),blood biochemical indicators(blood glucose,blood lipids,and ion indicators),and cardiac structure and function indicators.Results General indicators for the 10～15 years and 16～20 years groups were compared.As age increased,the blood pressure and heart rate of female and male monkeys increased,and there was a significant difference in blood pressure changes between male monkeys.A comparison of two sets of blood biochemical indicators showed that,as age increased,blood glucose,triglycerides,total cholesterol,low-density lipoprotein cholesterol,blood calcium,blood sodium,and blood potassium increased,while lactate dehydrogenase decreased,in female and male monkeys.Among these,blood glucose,triglycerides(males),total cholesterol,high-density lipoprotein cholesterol(males),low-density lipoprotein cholesterol(males),blood calcium,blood sodium,blood potassium,and lactate dehydrogenase showed significant changes.A comparison of cardiac contractile function between the two groups showed that,as age increased,the anterior and posterior diameters of the left atrium significantly decreased in both female and male monkeys.Female monkeys showed a significant decrease in the interventricular septal end systolic diameter,left ventricular end diastole and systolic diameters,left ventricular end diastolic and systolic volumes,and left ventricular mass index,while no significant changes were seen in male monkeys.A comparison of diastolic function between the two groups showed that,as age increased,the late diastolic velocity of the mitral valve decreased significantly in male monkeys,while the early diastolic velocity of the left ventricular sidewall increased significantly in female monkeys.Correlation analysis was conducted between the metabolic indicators and the cardiac structure and function indicators of female and male monkeys.The correlations between metabolic indicators and cardiac structure and function indicators were weak in female monkeys,for which the maximum absolute Γ value did not exceed 0.39.However,the correlations between metabolic indicators and cardiac structure and function indicators were relatively strong in male monkeys,for which the maximum absolute Γ value reached 0.66.Conclusions Based on ultrasound analysis combined with metabolic indicators,the heart function of cynomolgus monkeys was studied,and basic data related to the structure and function of the heart in middle-aged and elderly cynomolgus monkeys were obtained.As age increased,blood glucose and lipid indicators increased in cynomolgus monkeys,while cardiac systolic and diastolic functions show a downward trend,similar to changes in middle-aged and older adult human populations.These data provide support for animal selection in research on age-related diseases related to heart function.

Objective To investigate the effects of calcitriol intervention on PI3K/AKT signaling pathway and wound healing in rats with diabetic foot ulcer(DFU).Methods Thirty-two male SD rats were divided into normal control(Con)group,DFU group,calcitriol low dose(L)group and calcitriol high dose(H)group.A circular wound of 5 mm in diameter and deep to the fascia was made on the dorsum of the left foot of rats in each group.HE staining was used to evaluate the histopathological changes of the wounds.Immunohistochemical method was selected to compare the distribution of CD34-positive cells and the expression of p-PI3K and p-AKT in traumatic tissues of each group.ELISA was adopted in the detection of serum IL-6,IFN-γ,TNF-α and IL-7.RT-PCR was used to detect the mRNA expression of PI3K and AKT in each group,and western blot was used to detect the protein expression of PI3K,p-PI3K,AKT,p-AKT and VEGF.Results Compared with Con group,the expressions of IL-6,IFN-γ,TNF-α,IL-7,CD34,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K,p-AKT/AKT increased,while PI3K protein expression decreased in DFU,L and H groups(P<0.05),VEGF and AKT protein expression decreased in DFV and L groups(P<0.05).Compared with DFU group,the expressions of VEGF,AKT and PI3K protein increased(P<0.05),while the expressions of p-PI3K/PI3K,p-AKT/AKT decreased in L and H groups(P<0.05),IL-6 decreased in L group(P<0.05),and CD34 expression increased in H group(P<0.05),while IL-6,IFN-γ,TNF-α and IL-7,PI3K mRNA,AKT mRNA,p-AKT protein and p-PI3K protein expression decreased(P<0.05).Compared with L group,the expressions of CD34,VEGF,AKT and PI3K protein increased(P<0.05),while IL-6,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K and p-AKT/AKT decreased in H group(P<0.05).Conclusions Calcitriol intervention may reduce the activity of the PI3K/AKT signaling pathway,inhibit inflammation,promote neovascularization,and facilitate wound healing in rats with DFU.

Autophagy， a mechanism of cell self-protection and self-renewal， is associated with the occurrence and development of lung cancer. Favorable autophagy can slow down the progression of lung cancer， while unfavorable autophagy can promote the progression. Therefore， regulating the level of autophagy is of great significance in the treatment of lung cancer. Healthy Qi deficiency and pathogenic Qi stagnation is an extension of the theory of deficiency and Qi stagnation proposed by the Academician WANG Yongyan. It refers to the pathological process that the abnormal body fluid metabolism caused by Qi deficiency of lung， spleen， and kidney results in phlegm and blood stasis. Lung cancer has the root cause of Qi deficiency of lung， spleen， and kidney and the syndrome of phlegm and blood stasis. The autophagy in lung cancer is interconnected with healthy Qi deficiency and pathogenic Qi stagnation. The Qi deficiency of lung， spleen， and kidney is the key factor for the weakening of favorable autophagy in lung cancer， which inhibits the apoptosis of tumor cells and leads to the accumulation of harmful substances. Phlegm and blood stasis is a direct factor enhancing the unfavorable autophagy in lung cancer， which promotes the autophagic death of normal cells， weakens the immunosuppressive effect of immune cells on tumor cells， and leads to the proliferation and migration of tumor cells. The combination of healthy Qi deficiency and pathogenic Qi stagnation results in the development of autophagy in an unfavorable direction and finally leads to the continuous progression of lung cancer. Therefore， the traditional Chinese medicine （TCM） treatment of lung cancer should follow the principle of reinforcing healthy Qi and expelling pathogenic Qi， removing phlegm and resolving stasis， so as to enhance favorable autophagy while inhibiting unfavorable autophagy. Such therapy can inhibit the proliferation and migration of tumor cells and promote the remission of lung cancer. According to the existing literature， Chinese medicine monomers are mainly used to treat lung cancer by regulating autophagy. The Chinese medicine intervention of autophagy in lung cancer mainly aims to promote the activation of autophagy. This may be because the favorable autophagy weakening caused by the Qi deficiency of lung， spleen， and kidney is the fundamental reason for the development of lung cancer.

Traditional Chinese medicine (TCM) equipment is the industry representative possessing independent intellectual property rights and unique Chinese characteristics. By integrating TCM and information technology, TCM equipment is experiencing an unprecedented period of opportunity. Here, based on the practical significance, we reviewed the recent series of policies to promote the TCM equipment development. In accordance, we analyzed the current main problems and causes, and finally put forward some policy demand and suggestions to boost TCM equipment industry.

Machine Learning ; Image Processing, Computer-Assisted/methods*