Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Background Permethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. Objective To observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. Methods HMC3 were treated with 0, 10, 25, and 55 μmol·L⁻¹ permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L⁻¹ permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L⁻¹ permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. Results HMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L⁻¹ permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L⁻¹ permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L⁻¹ compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L⁻¹ permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L⁻¹ permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L⁻¹ permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L⁻¹ permethrin groups (P<0.05). Conclusion Permethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.

Objective To assess the value of the MRI-based ovarian-adnexal reporting and data system (O-RADS MRI) for the diagnosis of adnexal masses. Methods A total of 407 patients who underwent dynamic contrast enhancement (DCE)-MRI and pathological examination (gold standard) at the Department of Radiology,Central Hospital of Wuhan between May 2017 and December 2022 were enrolled in this study.Two radiologists performed the O-RADS MRI scoring of adnexal masses according to MRI features and calculated the malignancy rate of adnexal masses by O-RADS MRI score,enhancement type,and mass type.Moreover,receiver operating characteristic curves were established to further evaluate the diagnostic values of O-RADS MRI score,enhancement type,and mass type for adnexal masses. Results A total of 502 adnexal masses were identified in the 407 patients enrolled in this study,including 364 benign masses and 138 malignant masses (including junctional masses).Radiologist 1 reported the malignancy rates of 0,0,5.4%,80.0%,and 89.7% and radiologist 2 reported the malignancy rates of 0,0,5.8%,86.2%,and 83.0% for the adnexal masses with the O-RADS MRI scores of 1-5,respectively.With O-RADS MRI ≥4 indicating malignant masses,the sensitivity,specificity,accuracy,positive predictive value,negative predictive value,false negative rate,and false positive rate were 94.2%,93.6%,93.8%,84.9%,97.7%,2.3%,and 15.1% for radiologist 1 and 93.4%,93.6%,93.6%,85.4%,97.4%,3.6%,and 14.6% for radiologist 2,respectively.The malignancy rates of the adnexal masses presenting no enhancement,cystic wall enhancement,type Ⅰ curve,type Ⅱ curve,and type Ⅲ curve were 0,1.3%,5.7%,81.2%,and 89.0% as reported by radiologist 1 and 0,1.2%,11.3%,87.6%,and 80.0% as reported by radiologist 2,respectively.The malignancy rates of the adnexal masses that were cystic lesions,cystic segregated lesions,solid lesions,cystic solid lesions,and cystic solid segregated lesions were 0,7.1%,38.7%,79.1%,and 89.8% as reported by radiologist 1 and 0,8.1%,37.8%,72.4%,and 89.6% as reported by radiologist 2,respectively.With type Ⅱ and type Ⅲ curves as the criteria for malignancy,the sensitivity of radiologists 1 and 2 was lower for cystic segregated lesions,both at 50.0%.For the masses containing solid components,radiologists 1 and 2 demonstrated low specificity,which was 57.7% and 56.5%,respectively.False-positive masses contained solid components and were mostly fibroadenomas or adnexal leiomyomas,while false-negative masses were mostly junctional cystadenomas with no or few solid components. Conclusions The O-RADS MRI risk stratification has a high diagnostic value for adnexal masses.Further evaluation and refinement are needed to reduce the false-positive rate.
Humans ; Female ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Adnexal Diseases/diagnosis* ; Ovarian Neoplasms/diagnosis* ; Ovary/pathology* ; Sensitivity and Specificity ; Middle Aged ; Adult ; Adnexa Uteri/diagnostic imaging* ; Young Adult ; Data Systems ; Aged

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.
Rats ; Animals ; Berberine/pharmacokinetics* ; Tissue Distribution ; Chromatography, Liquid ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/pharmacokinetics* ; Alkaloids/pharmacokinetics* ; Chromatography, High Pressure Liquid/methods* ; Arthritis

Objective: To propose a new staging system for presacral recurrence of rectal cancer and explore the factors influencing radical resection of such recurrences based on this staging system. Methods: In this retrospective observational study, clinical data of 51 patients with presacral recurrence of rectal cancer who had undergone surgical treatment in the Department of Gastrointestinal Surgery, Peking University People's Hospital between January 2008 and September 2022 were collected. Inclusion criteria were as follows: (1) primary rectal cancer without distant metastasis that had been radically resected; (2) pre-sacral recurrence of rectal cancer confirmed by multi-disciplinary team assessment based on CT, MRI, positron emission tomography, physical examination, surgical exploration, and pathological examination of biopsy tissue in some cases; and (3) complete inpatient, outpatient and follow-up data. The patients were allocated to radical resection and non-radical resection groups according to postoperative pathological findings. The study included: (1) classification of pre-sacral recurrence of rectal cancer according to its anatomical characteristics as follows: Type I: no involvement of the sacrum; Type II: involvement of the low sacrum, but no other sites; Type III: involvement of the high sacrum, but no other sites; and Type IV: involvement of the sacrum and other sites. (2) Assessment of postoperative presacral recurrence, overall survival from surgery to recurrence, and duration of disease-free survival. (3) Analysis of factors affecting radical resection of pre-sacral recurrence of rectal cancer. Non-normally distributed measures are expressed as median (range). The Mann-Whitney U test was used for comparison between groups. Results: The median follow-up was 25 (2-96) months with a 100% follow-up rate. The rate of metachronic distant metastasis was significantly lower in the radical resection than in the non-radical resection group (24.1% [7/29] vs. 54.5% [12/22], χ²=8.333, P=0.026). Postoperative disease-free survival was longer in the radical resection group (32.7 months [3.0-63.0] vs. 16.1 [1.0-41.0], Z=8.907, P=0.005). Overall survival was longer in the radical resection group (39.2 [3.0-66.0] months vs. 28.1 [1.0-52.0] months, Z=1.042, P=0.354). According to univariate analysis, age, sex, distance between the tumor and anal verge, primary tumor pT stage, and primary tumor grading were not associated with achieving R0 resection of presacral recurrences of rectal cancer (all P>0.05), whereas primary tumor pN stage, anatomic staging of presacral recurrence, and procedure for managing presacral recurrence were associated with rate of R0 resection (all P<0.05). According to multifactorial analysis, the pathological stage of the primary tumor pN1-2 (OR=3.506, 95% CI: 1.089-11.291, P=0.035), type of procedure (transabdominal resection: OR=29.250, 95% CI: 2.789 - 306.811, P=0.005; combined abdominal perineal resection: OR=26.000, 95% CI: 2.219-304.702, P=0.009), and anatomical stage of presacral recurrence (Type III: OR=16.000, 95% CI: 1.542 - 166.305, P = 0.020; type IV: OR= 36.667, 95% CI: 3.261 - 412.258, P = 0.004) were all independent risk factors for achieving radical resection of anterior sacral recurrence after rectal cancer surgery. Conclusion: Stage of presacral recurrences of rectal cancer is an independent predictor of achieving R0 resection. It is possible to predict whether radical resection can be achieved on the basis of the patient's medical history.
Humans ; Neoplasm Recurrence, Local/diagnosis* ; Rectal Neoplasms/therapy* ; Retrospective Studies ; Pelvis/pathology* ; Recurrence ; Treatment Outcome

Objective:To investigate the clinical and pathological characteristics and prognosis of upper tract urothelial carcinoma (UTUC) with concurrent other histological variants.Methods:The clinical data of 566 UTUC patients admitted to Peking University People's Hospital from January 2007 to April 2021 were retrospectively analyzed. Among them, 289 were males and 277 were females, with an average age of (67.3±10.0)years old. Among the patients, 97 had a history of smoking, 29 had undergone kidney transplantation, 120 had diabetes, 76 had coronary heart disease, 146 had hyperlipidemia, 271 had hypertension, and 50 had a history of chronic kidney disease. Among the UTUC cases, 366 had concurrent hydronephrosis, 55 had concurrent bladder cancer, and 43 had a history of previous bladder cancer. The distribution included 210 cases of renal pelvis carcinoma, 5 cases of carcinoma at the renal pelvis-ureter junction, 226 cases of ureteral carcinoma, and 125 cases of multifocal tumors. Patients were classified into the pure UTUC group and the UTUC with concurrent other histological variants group based on postoperative pathology, and their clinical and pathological features were compared. Logistic regression analysis was used to explore risk factors for the occurrence of histological variations in UTUC. The log-rank test was employed to compare the overall survival (OS) and cancer-specific survival (CSS) between the two groups, while Cox regression analysis was performed to investigate prognostic factors.Results:Among the 566 cases, 511 were pure UTUC and 55 were UTUC with concurrent other histological variants. Among the latter, 30 cases had squamous differentiation, 6 had glandular differentiation, 5 had mucinous differentiation, 5 had sarcomatoid carcinoma, 2 had micropapillary carcinoma, 2 had neuroendocrine carcinoma, 1 had giant cell carcinoma, and 4 had other mixed histological variations. The proportion of patients with a history of kidney transplantation was higher in the UTUC with concurrent histological variants group than that in the pure UTUC group [14.5% (8/55) vs. 4.1% (21/511)], with statistically significant difference ( P=0.003). In the UTUC with concurrent histological variants group, the proportion of postoperative high-grade tumors [98.2% (54/55) vs. 80.2% (410/511)], muscle-invasive tumors [89.1% (49/55) vs. 68.1% (348/511)], lymph node metastasis tumors [10.9% (6/55) vs. 2.3% (12/511)], and maximum tumor diameter [(3.60±2.64) cm vs. (2.96±1.98) cm] were higher than those in the pure UTUC group ( P<0.05). Multivariate logistic regression analysis showed that a history of kidney transplantation ( OR=4.991, 95% CI 1.749-13.615, P=0.002) was an independent predictive factor for the occurrence of histological variants. Follow-up was conducted for 1 to 174 months, with a median follow-up time of 32.8 months. UTUC with concurrent histological variants was significantly associated with worse OS and CSS ( P<0.05). Multivariate Cox regression analysis indicated that histological variants were an independent risk factor for OS ( HR=1.860, 95% CI 1.228-2.816, P=0.003) and CSS ( HR=2.146, 95% CI 1.349-3.412, P=0.001). Conclusions:UTUC with concurrent other histological variants exhibited higher postoperative tumor grade and stage compared to pure UTUC, and UTUC with concurrent other histological variants was an independent risk factor for worse prognosis.