With the development of society,the incidence of obesity has increased year by year in recent years,which has seriously jeopardized public health and safety,and has been a hot spot in the field of endocrine research.At the same time,obesity is also an important cause of a variety of metabolic diseases,such as metabolic syndrome,pre-diabetes,hypertension and polycystic ovary syndrome and other diseases,but the etiology and mechanism of obesity have not been completely clear,and basic research on obesity of traditional Chinese and western medicine still needs to be widely carried out.In this paper,animal models of obesity and its complications will be comprehensively summarized,and the model principles will be elaborated in combination with TCM syndromes and western medicine mechanisms,and evaluate their merits and demerits,so as to provide references for the selection of reasonable animal models for relevant experimental studies of obesity.

With the development of society,the incidence of obesity has increased year by year in recent years,which has seriously jeopardized public health and safety,and has been a hot spot in the field of endocrine research.At the same time,obesity is also an important cause of a variety of metabolic diseases,such as metabolic syndrome,pre-diabetes,hypertension and polycystic ovary syndrome and other diseases,but the etiology and mechanism of obesity have not been completely clear,and basic research on obesity of traditional Chinese and western medicine still needs to be widely carried out.In this paper,animal models of obesity and its complications will be comprehensively summarized,and the model principles will be elaborated in combination with TCM syndromes and western medicine mechanisms,and evaluate their merits and demerits,so as to provide references for the selection of reasonable animal models for relevant experimental studies of obesity.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 （Th17）/regulatory T cell （Treg） and Notch1 signaling pathway in mice with autoimmune thyroiditis （AIT）. MethodA total of 60 8-week-old NOD.H-2^h4 mice were randomly divided into the normal group， model group， western medicine group （selenium yeast tablet， 32.5 mg·kg^-1）， and low-dose （4.78 g·kg^-1·d^-1）， middle-dose （9.56 g·kg^-1·d^-1）， and high-dose （19 g·kg^-1·d^-1） Buzhong Yiqitang groups， with 10 mice in each group. The normal group was fed with distilled water， and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously， the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies （TGAb）， thyroid-stimulating hormone （TSH）， free triiodothyronine （FT3）， and free thyroid hormone （FT4） were detected by enzyme-linked immunosorbent assay （ELISA）， and thyroid tissue changes were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt （RORγt）， interleukin （IL）-17， forkhead box P3 （FoxP3）， IL-10， Notch1， and hair division-related enhancer 1 （Hes1） in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the normal group， the thyroid structure of the model group was severely damaged， and lymphocytes were infiltrated obviously. The levels of serum TGAb， FT3， and FT4 contents were significantly increased， and TSH content was significantly decreased （P<0.01）. The mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were significantly increased， while those of FoxP3 and IL10 were significantly decreased in the model group （P<0.01）. Compared with the model group， thyroid structural damage and lymphocyte infiltration were improved in the treatment groups， and serum TGAb， FT3， and FT4 contents were significantly decreased. TSH content was increased， and mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees （P<0.05， P<0.01）， and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice， and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.

Objective:To investigate the effects of insulin-like growth factor-binding protein 3(IGFBP3),which is carried in exosomes released by cisplatin(DDP)-tolerant human lung adenocarcinoma(LUAD)A549/DDP cells,on differentiation of macrophages and its effect on DDP resistance of A549 cells.Methods:The parental A549 and A549/DDP cells were cultured in vitro,and the IC50 values were calculated after treatment with different concentrations of DDP for 48 h.The supernatants of A549 or A549/DDP cells culture were collected,and the exosomes were isolated using ultracentrifugation and named A-exo or A/D-exo,respectively.THP-1 cells were induced to differentiate into M0-type macrophages with PMA(15 μg/mL),mixed with A549 cells at a ratio of 1∶1,and then inoculated in the axillae of nude mice;on the day of tumor cell inoculation,the tumor cells were injected with PBS,A-exo,and A/D-exo at the inoculation site of the tumor cells,respectively,and at the same time,the treatment was carried out by intraperitoneal injection of DDP 1 time every 4 d.On the 35th day of the tumor loading in mice,the recruitment of human CD11b+CD206+or CD11b+CD86+macrophages in transplanted tumor tissues was detected by flow cytometry(FCM).Antibody microarrays were used to screen for proteins carried by A-exo or A/D-exo and validated by detecting the amount of IGFBP3 protein in A-exo and A/D-exo by ELISA method.A549 or A549/DDP cells were treated with different concentrations of rhIGFBP3,and the effects of rhIGFBP3 on the proliferation or migration ability of the cells were detected by MTS assay and Transwell assay,respectively.M0-type macrophages were treated with rhIGFBP3 for 4 d,and the culture supernatant was collected;the effects of different concentrations of rhIGFBP3 on the production of TGF-β and TNF-α content by M0-type macrophages were detected by ELISA;in addition,A549 cells were treated with rhIGFBP3 or culture supernatant of M0-type macrophages pretreated with rhIGFBP3,and again detected the IC50 value of DDP on A549 cells.Results:The IC50 value of DDP on A549/DDP cells was significantly higher than that of A549 cells(P<0.01);A/D-exo significantly promoted the growth of A549 cells xenograft tumors(P<0.05)and facilitated the recruitment of CD11b+CD206+macrophages into tumor tissues(P<0.05),compared with PBS and A-exo groups.Exosomes A-exo and A/D-exo were successfully obtained;high levels of IGFBP3 were carried in A/D-exo compared with A-exo.The analysis showed that the expression level of IGFBP3 was significantly up-regulated in patients with LUAD,and the overall survival rate of patients with high expression of IGFBP3 was reduced compared with those with low expression of IGFBP3.High concentration of rhIGFBP3(100 ng/mL)had a significant pro-proliferative effect on either A549 or A549/DDP cells(both P<0.05),but there was no statistically significant effect on the migratory ability of A549 or A549/DDP cells.High concentrations of rhIGFBP3(100 ng/mL)induced TGF-β1 production by M0-type macrophages(P<0.05),but not TNF-α production.The IC50 value of DDP on A549 cells was significantly increased(P<0.05)after treatment with culture supernatant of M0-type macrophages pretreated with IGFBP3(but not rhIGFBP3).Conclusion:A549/DDP cells mediate M2-type macrophage differentiation and promote secondary drug resistance in A549 cells by secreting IGFBP3-rich exosomes.

Objective:To investigate the effects of insulin-like growth factor-binding protein 3(IGFBP3),which is carried in exosomes released by cisplatin(DDP)-tolerant human lung adenocarcinoma(LUAD)A549/DDP cells,on differentiation of macrophages and its effect on DDP resistance of A549 cells.Methods:The parental A549 and A549/DDP cells were cultured in vitro,and the IC50 values were calculated after treatment with different concentrations of DDP for 48 h.The supernatants of A549 or A549/DDP cells culture were collected,and the exosomes were isolated using ultracentrifugation and named A-exo or A/D-exo,respectively.THP-1 cells were induced to differentiate into M0-type macrophages with PMA(15 μg/mL),mixed with A549 cells at a ratio of 1∶1,and then inoculated in the axillae of nude mice;on the day of tumor cell inoculation,the tumor cells were injected with PBS,A-exo,and A/D-exo at the inoculation site of the tumor cells,respectively,and at the same time,the treatment was carried out by intraperitoneal injection of DDP 1 time every 4 d.On the 35th day of the tumor loading in mice,the recruitment of human CD11b+CD206+or CD11b+CD86+macrophages in transplanted tumor tissues was detected by flow cytometry(FCM).Antibody microarrays were used to screen for proteins carried by A-exo or A/D-exo and validated by detecting the amount of IGFBP3 protein in A-exo and A/D-exo by ELISA method.A549 or A549/DDP cells were treated with different concentrations of rhIGFBP3,and the effects of rhIGFBP3 on the proliferation or migration ability of the cells were detected by MTS assay and Transwell assay,respectively.M0-type macrophages were treated with rhIGFBP3 for 4 d,and the culture supernatant was collected;the effects of different concentrations of rhIGFBP3 on the production of TGF-β and TNF-α content by M0-type macrophages were detected by ELISA;in addition,A549 cells were treated with rhIGFBP3 or culture supernatant of M0-type macrophages pretreated with rhIGFBP3,and again detected the IC50 value of DDP on A549 cells.Results:The IC50 value of DDP on A549/DDP cells was significantly higher than that of A549 cells(P<0.01);A/D-exo significantly promoted the growth of A549 cells xenograft tumors(P<0.05)and facilitated the recruitment of CD11b+CD206+macrophages into tumor tissues(P<0.05),compared with PBS and A-exo groups.Exosomes A-exo and A/D-exo were successfully obtained;high levels of IGFBP3 were carried in A/D-exo compared with A-exo.The analysis showed that the expression level of IGFBP3 was significantly up-regulated in patients with LUAD,and the overall survival rate of patients with high expression of IGFBP3 was reduced compared with those with low expression of IGFBP3.High concentration of rhIGFBP3(100 ng/mL)had a significant pro-proliferative effect on either A549 or A549/DDP cells(both P<0.05),but there was no statistically significant effect on the migratory ability of A549 or A549/DDP cells.High concentrations of rhIGFBP3(100 ng/mL)induced TGF-β1 production by M0-type macrophages(P<0.05),but not TNF-α production.The IC50 value of DDP on A549 cells was significantly increased(P<0.05)after treatment with culture supernatant of M0-type macrophages pretreated with IGFBP3(but not rhIGFBP3).Conclusion:A549/DDP cells mediate M2-type macrophage differentiation and promote secondary drug resistance in A549 cells by secreting IGFBP3-rich exosomes.

FACTORS ASSOCIATED WITH PAROXYSMAL VERTIGO AMONG URBAN-DWELLERS AGED 55 YEARS AND OVER IN THE MALAYSIAN ELDERS LONGITUDINAL RESEARCH (MELOR) STUDY Background: Paroxysmal Vertigo (PV) negatively affects life quality and increases in prevalence with age, but the risk factors remain inconclusive. Objective: The present study aimed to investigate the risk factors of PV among a multi-ethnic urban population in late mid-life and late life within a middle-income Southeast-Asian country. Methods: Cross-sectional data from the first wave of the Malaysian Elders Longitudinal Research (MELoR) study were utilized for this study involving randomly sampled participants aged 55 years and over. Socio-demographics, comorbidities, and psychological status were obtained through home-based computer-assisted interviews. Results: Based on an analysis of 1530 participants, mean age (SD) = 68.81 (7.49), 64.9% female; 32.9% Malay, 34.6% Chinese), the lifetime prevalence of PV was 12.1%. The risk factors associated based on multivariate analysis were hypertension, osteoarthritis, depression, and vitamin B12 Deficiency. Chinese ethnicity (OR = 0.582; 95% CI = 0.390 to 0.870) and smoking (OR = 0.377; 95% CI = 0.223 to 0.637) were protective factors against PV. Conclusions: While the risk factors reported are similar to other studies, the lower prevalence of PV among ethnic Chinese and smokers had not previously been reported. Our study highlighted potential genetic and lifestyle links to PV which should be evaluated in future studies.

In the past decades,numerous chemical analysis studies have identified numerous compounds in tobacco smoke,and the number is increasing,as of 2013,9582 compounds have been identified in tobacco smoke,including nicotine,tobacco smoke-specific nitrosamines,benzo[alpha]pyrene and other substances,as well as cotinine,4-(methylnitrosamine)-1-(3-pyridyl)-1-butanol and other products that are metabolized in the body.The products of metabolic transformation,such as cotinine and 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanol,can target the heart,lungs and other organs,inducing chronic obstructive pulmonary disease,coronary heart disease,lung cancer,esophageal cancer and other types of cancer.Chinese medicine's understanding of"toxicity"originates from the Nei Jing,which believes that"poisonous evil"can be an external pathogenic factor,but can also cause the five organs to lose harmony and produce phlegm and stagnation and other pathological products that accumulate into internal toxicity.The modern medical understanding of tobacco smoke toxic substances and their metabolites is quite consistent with the understanding of"external toxicity"and"internal toxicity"in Chinese medicine,so the author intends to explore the main components and pathogenic mechanisms of tobacco smoke harmful substances and their metabolites.To clarify the etiological characteristics and pathogenic transformation characteristics of"internal"and"external"tobacco smoke toxicity,so as to explore the modernization of"tobacco smoke toxicity"and the combination of tobacco smoke pathogenesis and TCM theory for TCM.Theoretical foundation is laid.

METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.