Chronic constipation is a highly debilitating condition, affecting a significant proportion of the commu-nity. Rhei Radix et Rhizoma (rhubarb) is one of the important herbal drugs used in traditional Chinese medicine (TCM) for treating constipation which includes four groups of main active components such as free anthraquinone, conjunc-tive anthraquinone, rhubarb tannin, and rhubarb polysaccharides. However, which one is response for the laxative effect of rhubarb is unknown. Therefore, we proposed a strategy for the effect-guided quality control of TCM based on disease. The effective material for laxative effect of rhubarb was firstly screened based on the constipation model. And different production locations were investigated. Then, the processing was optimized to set up a quality control of rhubarb. It was found that the bioactive component was the conjunctive anthraquinone for the laxative effect. And the raw herb from Liangshan had the best quality compared with those from Pingwu and Beichuan in Sichuan Prov-ince, China. The extraction ethanol volumes to substrate ratio of 10.34, extraction time of 24.25 min and extraction number of 4 were the best conditions for the extraction of conjunctive anthraquinone. Under the optimized condi-tions, the maximum production was 5.455 mg·g-1. This extraction procedure was used as quality control of rhubarb in the treatment of constipation.

Objective: To investigate the urban and rural differences in adverse outcomes of pulmonary tuberculosis (PTB) in patients with pulmonary tuberculosis-diabetes mellitus comorbidity (PTB-DM), so as to provide insights into improving the prevention and treatment measures for PTB-DM. Methods: Patients with PTB-DM who were admitted and discharged from 14 designated tuberculosis hospitals in Hangzhou City from 2018 to 2022 were selected. Basic information, and history of diagnosis and treatment were collected through hospital information systems. The adverse outcomes of PTB were defined as endpoints, and the proportions of adverse outcomes of PTB in urban and rural patients with PTB-DM were analyzed. Factors affecting the adverse outcomes of PTB were identified using a multivariable Cox proportional hazards regression model. Results: A total of 823 patients with PTB-DM were enrolled, including 354 (43.01%) urban and 469 (56.99%) rural patients. There were 112 (13.61%) patients with adverse outcomes of PTB. The proportions of adverse outcomes of PTB in urban and rural patients were 14.41% and 13.01%, respectively, with no statistically significant difference (P>0.05). Multivariable Cox proportional hazards regression analysis identified first diagnosed in county-level hospitals or above (HR=2.107, 95%CI: 1.181-3.758) and drug resistance (HR=3.303, 95%CI: 1.653-6.600) as the risk factors for adverse outcomes of PTB in urban patients with PTB-DM, while the treatment/observed management throughout the process (HR=0.470, 95%CI: 0.274-0.803) and fixed-dose combinations throughout the process (HR=0.331, 95%CI: 0.151-0.729) as the protective factors for adverse outcomes in rural patients with PTB-DM. Conclusions There are differences in influencing factors for adverse outcomes of PTB in urban and rural patients with PTB-DM. The adverse outcomes of PTB are associated with first diagnosed hospitals and drug resistance in urban patients, and are associated with the treatment/observed management and fixed-dose combinations throughout the process in rural patients.

Objective:To construct a nomogram model for predicting the progression-free survival (PFS) of patients with positive Rictor protein tested in lesion tissues of D2 + radical gastric adenocarcinoma resection and to analyze its predictive value. Methods:The tissue samples of 1 366 gastric adenocarcinoma patients who underwent radical resection in Shanxi Province Cancer Hospital from May 2005 to December 2020 were retrospectively collected, and the Rictor protein expression was detected by using the immunohistochemical SP method. The 676 Rictor-positive cases were grouped in a 7∶3 ratio by simple randomization, including 496 cases in the training cohort and 180 cases in the validation cohort. The correlation of Rictor protein expression and other clinicopathological factors with PFS of Rictor-positive patients was analyzed by using a multifactorial Cox proportional risk model to determine the independent influencing factors of PFS. The nomogram for predicting the 3-year and 5-year PFS rates of patients with gastric adenocarcinoma was constructed based on the independent influencing factors of PFS. The constructed nomogram was bootstrapped with 1 000 resamplings for internal validation to test the accuracy of the prediction model. The internal and external predictive efficacy of the model was further assessed by calibration curves, area under the curve (AUC) of time-dependent receiver operating characteristic (ROC) and decision curve analysis (DCA). The nomogram model was applied to score the PFS of 496 cases in the training cohort, and the X-tile software was used to obtain the best cut-off value for the score. The overall cohort, training cohort and validation cohort cases were divided into low-risk group (≤ best cut-off value) and high-risk group (> best cut-off value) according to the best cut-off value, and the Kaplan-Meier method was used to analyze the difference in PFS between the low-risk group and high-risk group.Results:Multifactorial Cox regression analysis showed that gender, age, pT stage, number of positive lymph nodes, neural invasion, tumor longest diameter, omental invasion, Clavien-Dindo classification of postoperative complications, and CGA expression were independent influencing factors for PFS of the training cohort with Rictor-positive gastric adenocarcinoma. The nomogram for predicting the 3-year and 5-year PFS rates of patients with Rictor-positive gastric adenocarcinoma was constructed based on the above indicators. The calibration curve for internal validation and external validation showed good agreement between the prediction of nomogram and actual PFS. The time-ROC curve showed that the AUC of the internally validated and externally validated models for predicting the 3-year PFS rate was 0.834 (95% CI 0.746-0.823) and 0.799 (95% CI 0.699-0.868), and the AUC for predicting the 5-year PFS rate was 0.817 (95% CI 0.718-0.821) and 0.795 (95% CI 0.675-0.895). The C index of the model for overall prediction was 0.795 (95% CI 0.764-0.825), which was better than the 8th edition of American Joint Committee on Cancer (AJCC) TNM staging [0.693 (95% CI 0.662-0.723)]; the external validation DCA showed that the C index of the model for prediction was 0.769 (95% CI 0.718-0.821). The X-tile software analysis showed that the best cut-off value for the PFS score of the training cohort model was 265.08, with 457, 337 and 120 cases in the low-risk group and 219, 159 and 60 cases in the high-risk group for the overall cohort, training cohort and validation cohort, respectively. Kaplan-Meier survival analysis showed that the median PFS time was not reached in the low-risk group for the overall cohort, training cohort and validation cohort, and the median PFS time was 24, 24 and 28 months in the high-risk group, and there were statistical differences in PFS between the low-risk and high-risk groups for each cohort (all P < 0.001). Conclusions:For the first time, a nomogram model for PFS prediction in gastric adenocarcinoma patients with Rictor-positive expression is successfully constructed, which could better distinguish between patients with low-risk and high-risk of PFS. For high-risk patients with Rictor-positive gastric adenocarcinoma, in addition to controlling tumor metastasis and postoperative complications, attention should be paid to the targeted therapy for positive expression of Rictor.

Uranium is an important radioactive actinide in nature and an important nuclear material in nuclear industry. After uranium is accidentally released into the environment, it enters the body through the respiratory tract, the digestive tract, and other ways, then enters the circulation system through blood, and is finally mainly deposited in the kidney and bone, causing a certain degree of toxicity. Therefore, efficient low-toxicity chelators are an important way to reduce radionuclide pollution, radiation damage, and chemical toxicity. This article reviews uranium deposition and harm, the detoxification mechanism of uranium chelators, and the research advances in uranium chelators and points out the development trend of uranium chelators.

Objective:To investigate the biological characteristics of triple negative breast cancer (TNBC) with low expression of HER2 (HER2-low).Methods:A total of 93 TNBC cases in Shanxi Cancer Hospital from 2017 to 2019 were collected and divided into HER2-negative and HER2-low groups according to HER2 expression status. The clinicopathological features and prognostic differences between the two groups were retrospectively analyzed and compared, and genetic detection of tumor tissues was performed to clarify somatic mutation status and differences between the two groups.Results:Ninety-three patients aged 26 to 86 years were enrolled, including 60 patients in the HER2-negative group and 33 patients in the HER2-low group. The distribution of HER2-low in luminal androgen receptor (LAR) subtype (14/23, 60.87%) and non-LAR subtype (19/70, 27.14%) was significantly different ( P=0.005). There were no significant differences in age, pT stage, histological grade, infiltration mode, lymph node metastasis and survival analysis. The expression of HER2-low in the tumor was heterogeneous, including different proportions of weak, weak to moderate intensity, and incomplete to intact membrane staining. With the change of the proportion of HER2-positive cells, the different distribution of those cells in the total tumor cells was noted, including cluster, mosaic and scattered patterns. The concentration and quality of DNA extracted from 71 of the 93 samples met the requirements for making libraries, including 43 in the HER2-negative group and 28 in the HER2-low group. Genetic mutations were mainly missense mutations, single nucleotide mutations, and point mutations in which base C was replaced by base T. There was no significant difference in genes with mutation frequency>3 times between the two groups. CTNNB1 and FGFR3 genes were only mutated in HER2-low group; while ALK, CYP2D6 and FAT1 genes were only mutated in HER2-negative group. HER2-low group included 18 HER2 1+ cases and 10 HER2 2+ cases. Genes with mutation frequency>3 times between the two groups included PIK3CA, TP53, SLX4, ATM and BRCA1. The mutation frequency of PIK3CA in HER2 2+ was significantly higher than that in HER2 1+ group ( P<0.05), and SLX4 gene was only mutated in HER2 1+ group. Conclusions:There are some differences of histological morphology and genetic variation between HER2-negative group and HER2-low group, and also differences in genetic variation between HER2 1+ and HER2 2+ in HER2-low group, which are helpful for more accurate stratification of TNBC and useful for finding the therapeutic target and precise treatment of HER2-low TNBC.

Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent proteinuria and progressive decline in renal function, and is one of the microvascular complications of diabetes. With the in-depth understanding of the pathogenesis of DN, the role of intestinal flora imbalance in the disease has been found clinically. This suggests that restoring the host′s healthy gut flora may be a means of improving DN. In fact, recent studies have shown that many of the drugs currently used to treat DN affect gut microbiota composition. In this review, intestinal flora is regarded as one of the main factors affecting the development of DN, and DN therapy targeting intestinal flora is summarized to provide new ideas for the diagnosis and treatment of DN.