Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

Objective To investigate the epidemiological characteristics and identify the risk factors of Giardia lamblia infections among patients with colorectal cancer in Henan Province. Methods A cross-sectional study was performed for questionnaire surveys among colorectal cancer patients in Henan Cancer Hospital during the period from March to July, 2021. Patients’ stool samples were collected, and the triosephosphate isomerase (tpi) gene of G. lamblia was amplified in stool samples using nested PCR assay to characterize the parasite genotype. Univariate analysis and multivariate logistic regression analyses were employed to identify the risk factors of G. lamblia infections among colorectal cancer patients. Results A total of 307 colorectal cancer patients were investigated, including 176 males (57.3%) and 131 females (42.7%). PCR assay detected 8.1% [95% confidential interval (CI): (0.056, 0.117)] prevalence of G. lamblia infections among the study subjects, and there was no significant difference in the prevalence between men [9.1%, 95% CI: (0.057, 0.143)] and women [6.9%, 95% CI: (0.037, 0.125)] (χ² = 0.495, P = 0.482). In addition, there was no age-specific prevalence of G. lamblia infections among the participants (χ² = 1.534, P = 0.675). Multivariate logistic regression analysis identified use of septic tanks [odds ratio (OR) = 3.336, 95% CI: (1.201, 9.267)], daily use of well water [OR = 3.042, 95% CI: (1.093, 8.465)] and raising livestock [OR = 3.740, 95% CI: (1.154, 12.121)] as risk factors of G. lamblia infections among colorectal cancer patients, and the prevalence of abdominal pain was significantly greater in colorectal cancer patients with G. lamblia infections than in those without infections (P = 0.017). Among the 25 patients with G. lamblia infections, assemblage A was characterized in 24 (96.0%) cases and assemblage B in one case (4.0%). Conclusions The prevalence of G. lamblia is high among colorectal cancer patients in Henan Province, and assemblage A is the dominant genotype of G. lamblia. Use of septic tanks, daily use of well water and raising livestock are risk factors of G. lamblia infections among patients with colorectal cancer.

Objective:To understand the current situation of hospice care attitude among nursing students in Tibet university, to analyze the factors affecting nursing students' attitude towards hospice care; put forward the intervention measures to promote the development of hospice care ability.Methods:From June to August, 2019, 194 nursing undergraduates from Medical College of Tibet University were surveyed by questionnaire, including the Chinese version of the Frommelt Hospice care attitude scale (Fatcod-B), the Caring Ability evaluation scale (CAI), and the general nursing students questionnaire. SPSS 24.0 was used to transcribe and statistically analyze the data.Results:The total score of the hospice care attitude of nursing students was (93.56±7.42), the average score of items was (3.22 ± 0.25), and the highest score of caring attitude was (3.68 ± 0.56), the attitude dimension score of communication with terminal patients was the lowest (2.66 ± 0.42). The ability of nursing students to care for others, the degree of death topic discussion and the experience of other people's death can influence their palliative care attitude.Conclusions:The attitude of the undergraduate nursing students in Tibet is above the middle. Palliative care, and the nursing students' caring ability and communication ability should be improved by strengthening the practical experience and education and training, so as to promote the development of the students' palliative care ability.

Objective:To understand the iodine nutritional status of Tibet residents and provide a scientific basis for prevention and treatment of iodine deficiency disorders in Tibet.Methods:A cross-sectional survey was conducted in 67 counties (districts) of 7 cities of Tibet. Each county (district) was divided into 5 sampling areas according to its east, west, south, north and middle location, and 1 township (town) was selected from each sampling area. Four administrative villages were selected from each township (town), and 15 household's salt samples were sampled for salt iodine detection. Twenty pregnant women and 1 primary school were selected from each township (town). Forty non-boarding children aged 8-10 years (half male and half female) were selected from each primary school, urine samples were collected for urinary iodine detection. Thyroid volume was also measured in children aged 8 to 10 years in 3 cities.Results:In 2018, the median of salt iodine in Tibet was 25.33 mg/kg (22 136 samples). The coverage rate of iodized salt, the qualified rate of iodized salt and the consumption rate of qualified iodized salt were 97.75% (21 637/22 136), 87.00% (18 824/21 637) and 85.04% (18 824/22 136), respectively. The difference between 7 cities were statistically singnificant ( P < 0.01). Naqu City had the lowest levels [92.03% (2 923/3 176), 69.41% (2 029/2 923), 63.89% (2 029/3 176)]. The median of urinary iodine of 13 516 children aged 8-10 years was 187.0 μg/L. The urinary iodine of boys was 188.6 μg/L, girls was 185.6 μg/L. The median of urinary iodine of 2 920 pregnant women was 165.6 μg/L. The differences in urinary iodine of pregnant women in different pregnancy periods were statistically significant ( H=13.33, P < 0.01). The urinary iodine of pregnant women was the highest in early pregnancy (178.9 μg/L) and the lowest in late pregnancy (162.3 μg/L). The goiter rate of children aged 8-10 years was 1.01% (34/3 364). The goiter rate of children in different cities was different (χ 2=59.28, P < 0.01), and Changdu had the highest (4.25%, 17/400). Conclusions:In 2018, the consumption rate of qualified iodized salt among Tibet residents is relatively low, and the comprehensive prevention and control measures of iodine deficiency disorders need to be further strengthened. We should strengthen the monitoring of iodine nutrition level of pregnant women at different stages of pregnancy, strengthen health education and raise the awareness of prevention and treatment of iodine deficiency disorders among residents.

Objective:To investigate and analyze the current situation, screening, clinical characteristics, prevention and treatment of bleeding esophageal varices in cirrhotic patients with portal hypertension in Tibet region.Methods:Clinical data of cirrhotic patients with portal hypertension through March 2017 to February 2020 from Tibet region were collected and analyzed retrospectively.Results:511 cases with liver cirrhosis were included in the study, of which 185 cases (36.20%) had compensated cirrhosis and 326 cases (63.80%) had decompensated cirrhosis. Further analysis of the etiological data of liver cirrhosis showed that 306 cases (59.88%) were of chronic hepatitis B, 113 cases (22.11%) of alcoholic liver disease, and 68 cases (13.31%) of chronic hepatitis B combined with alcoholic liver disease. Among patients with compensated liver cirrhosis, 48 cases (25.95%) underwent endoscopic examination of which 33 diagnosed as high-risk variceal bleeding. However, none of these 33 cases had received non-selective β-blocker therapy, and only four patients had received endoscopic variceal banding therapy. Among patients with decompensated liver cirrhosis, 83 cases (25.46%) had a history of upper gastrointestinal bleeding, 297 cases (91.10%) had ascites, 23 cases (7.05%) had hepatic encephalopathy, and 3 cases (0.92%) had hepatorenal syndrome. Among the patients with a history of upper gastrointestinal bleeding, 42 cases (50.60%) had received secondary preventive treatment for bleeding esophageal varices, including 39 cases of endoscopic treatment, 1 case of endoscopic combined drug treatment, 3 cases of interventional treatment, and 2 cases of surgical treatment.Conclusion:Chronic hepatitis B and alcoholic liver diseases are the main causes of liver cirrhosis in Tibet region. Moreover, this region lacks screening, prevention and treatment for bleeding esophageal varices in cirrhotic patients with portal hypertension. Therefore, it is necessary to increase the screening of high-risk groups to prevent and improve the first-time bleeding, and promote multidisciplinary team to prevent and treat re-bleeding.

Objective: To screen out active ingredients, and predict the anti-cancer targets of Ligustri Lucidi Fructus-Astragali Radix based on the "herbs-active ingredient-action targets" network. Method: The traditional Chinese medicine (TCM) system pharmacology platform (TCMSP) was employed to screen out the active ingredients and putative targets of anti-cancer of glossy privet fruit and astragalus. DisGeNET database and Online Mendelian Inheritance in Man (OMIM database) were employed to predict the targets for treating cancer, and then "herbs-active ingredients-key targets" network was constructed by using Cytoscape software. The omicshare platform was employed to match the putative targets of ingredients and the targets for treating cancer. Finally, the protein interaction network of key targets was constructed by using String database, and the analysis of biological functions and pathways of them was carried out by using DAVID database. Result: Totally 33 drug active ingredients were screened out, involving a total of 203 targets, and 14 of them were related to cancer. These 14 key targets played an therapeutic role in treating cancer by regulating target proteins, such as ERBB2, AR, SRC, EGFR, ESR1, as well as proteoglycans in cancer, cancer pathways, microRNAs in cancer and other pathways. Conclusion: The therapeutic mechanism of Ligustri Lucidi Fructus-Astragali Radix reflects the multi-component, multi-target, and multi-pathway characteristics of TCMs, providing the scientific basis for further study and the material basis of Ligustri Lucidi Fructus-Astragali Radix against cancer.

BACKGROUNDAcute abdominal pain is a common symptom of emergency patients. The severity was always evaluated based on physicians' clinical experience. The aim of this study was to establish an early risk stratification method (ERSM) for addressing adults with acute abdominal pain, which would guide physicians to take appropriate and timely measures following the established health-care policies.

METHODSIn Cohort 1, the records of 490 patients with acute abdominal pain that developed within the past 72 h were enrolled in this study. Measurement data and numeration data were compared with analysis of variance and Chi-square test, respectively. Multiple regression analysis calculated odd ratio (OR) value. P and OR values showed the impacts of factors. ERSM was established by clinical experts and statistical experts according to Youden index. In Cohort 2, data from 305 patients with acute abdominal pain were enrolled to validate the accuracy of the ERSM. Then, ERSM was prospectively used in clinical practice.

RESULTSThe ERSM was established based on the scores of the patient's clinical characteristics: right lower abdominal pain + 3 × diffuse abdominal pain + 3 × cutting abdominal pain + 3 × pain frequency + 3 × pain duration + fever + 2 × vomiting + 5 × stop defecation + 3 × history of abdominal surgery + hypertension history + diabetes history + hyperlipidemia history + pulse + 2 × skin yellowing + 2 × sclera yellowing + 2 × double lung rale + 10 × unconsciousness + 2 × right lower abdominal tenderness + 5 × diffuse abdominal tenderness + 4 × peritoneal irritation + 4 × bowel sounds abnormal + 10 × suspicious diagnosis + white blood cell count + hematocrit + glucose + 2 × blood urea nitrogen + 3 × creatine + 4 × serum albumin + alanine aminotransferase + total bilirubin + 3 × conjugated bilirubin + amylase. When the score was <18, the patient did not need hospitalization. A score of ≥18 and <38 indicated that the patient should be under observation or hospitalized. A score of ≥38 and <50 indicated the need for an emergent operation. A score of ≥50 indicated the need for admission to the Intensive Care Unit. The area under the receiver operating characteristic curve of the ERSM in Cohorts 1 and 2 were 0.979 and 0.988, respectively.

CONCLUSIONSThis ERSM was an accurate and reliable method for making an early determination of the severity of acute abdominal pain. There was the strong correlation between scores of ERSM and health-care decision-making.

Abdominal Pain ; diagnosis ; Adult ; Aged ; Aged, 80 and over ; Chi-Square Distribution ; Cohort Studies ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; ROC Curve ; Risk Assessment ; methods ; Risk Factors ; Young Adult

Aged ; Central Nervous System Neoplasms ; pathology ; Humans ; Lymphoma, Non-Hodgkin ; pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged

This study was aimed to establish a stable animal model of left ventricular hypertrophy (LVH) to provide theoretical and experimental basis for understanding the development of LVH. The abdominal aorta of male Wistar rats (80-100 g) was constricted to a diameter of 0.55 mm between the branches of the celiac and anterior mesenteric arteries. Echocardiography using a linear phased array probe was performed as well as pathological examination and plasma B-type natriuretic peptide (BNP) measurement at 3, 4 and 6 weeks after abdominal aortic constriction (AAC). The results showed that the acute mortality rate (within 24 h) of this modified rat model was 8%. Animals who underwent AAC demonstrated significantly increased interventricular septal (IVS), LV posterior wall (LVPWd), LV mass index (LVMI), cross-sectional area (CSA) of myocytes, and perivascular fibrosis; the ejection fraction (EF), fractional shortening (FS), and cardiac output (CO) were consistently lower at each time point after AAC. Notably, differences in these parameters between AAC group and sham group were significant by 3 weeks and reached peaks at 4th week. Following AAC, the plasma BNP was gradually elevated compared with the sham group at 3rd and 6th week. It was concluded that this modified AAC model can develop LVH, both stably and safely, by week four post-surgery; echocardiography is able to assess changes in chamber dimensions and systolic properties accurately in rats with LVH.
Animals ; Aorta, Abdominal ; pathology ; Constriction, Pathologic ; complications ; Disease Models, Animal ; Echocardiography ; methods ; Enzyme-Linked Immunosorbent Assay ; Heart ; physiopathology ; Hypertrophy, Left Ventricular ; blood ; etiology ; pathology ; Male ; Myocardium ; pathology ; Natriuretic Peptide, Brain ; blood ; Rats, Wistar ; Time Factors

Water soluble extract (WSE) is an important index for the quality evaluation of Astragali Radix (AR). In this study, the WSE of the wild AR from Shanxi province (SX) and the cultivated AR from Gansu Province (GS) were compared. The WSEs of two types of AR were determined according to the appendix of Chinese pharmacopoeia. Then the WSEs were subjected to NMR analysis, and the obtained data were analyzed using HCA, PCA, OPLS-DA, microarray analysis, and Spearman rank analysis. In addition, the Pearson correlation of differential metabolites were also calculated. The results showed that the WSE content of GS-AR (37.80%) was higher than that of SX-AR (32.13%). The main constituent of WSE was sucrose, and other 18 compounds, including amino acids, organic acids, were also detected. Multivariate analysis revealed that SX-AR contained more choline, succinic acid, citric acid, glutamate, taurine and aspartate, while GS samples contained more sucrose, arginine and fumaric acid. In addition, the Pearson correlations between different metabolites of the two types of AR also showed apparent differences. The results suggested that the WSE of two types of AR differs not only in the content, but also in the chemical compositions. Thus, the cultivation way is important to the quality of AR. This study supplied a new method for the comparison of extract of herbal drugs.
Arginine ; analysis ; Aspartic Acid ; analysis ; Choline ; analysis ; Citric Acid ; analysis ; Drugs, Chinese Herbal ; analysis ; chemistry ; Fumarates ; analysis ; Glutamic Acid ; analysis ; Magnetic Resonance Spectroscopy ; Multivariate Analysis ; Phylogeography ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Succinic Acid ; analysis ; Sucrose ; analysis ; Taurine ; analysis