Poly-G for tumor matched samples chronicles the evolution of human colorectal cancer / 中华肿瘤杂志

Objective: To analyze poly-guanine (poly-G) genotypes and construct the phylogenetic tree of colorectal cancer (CRC) and provide an efficient and convenient method for the study of intra-tumor heterogeneity and tumor metastasis pathway. Methods: The clinicopathological information of patients with primary colorectal cancer resection with regional lymph node metastases were retrospectively collected in the Department of General Surgery, General Hospital of Tianjin Medical University from January 2017 to December 2017. The paraffin sections of the paired tumor samples were performed consecutively, and multi-region microdissection was performed after histogene staining. The phenol-chloroform extraction and ethanol precipitation scheme was used to obtain DNA, and Poly-G multiplex PCR amplification and capillary electrophoresis detection were performed. The correlation between Poly-G mutation frequency and clinicopathological parameters was analyzed. Based on the difference of Poly-G genotypes between paired samples, the distance matrix was calculated, and the phylogenetic tree was constructed to clarify the tumor metastasis pathway. Results: A total of 237 paired samples were collected from 20 patients including 134 primary lesions, 66 lymph node metastases, 37 normal tissues, and Poly-G mutation was detected in 20 patients (100%). The mutation frequency of Poly-G in low and undifferentiated patients was (74.10±23.11)%, higher than that in high and medium differentiated patients [(31.36±12.04)%, P<0.001]. In microsatellite instability patients, the mutation frequency of Poly-G was (68.19±24.80)%, which was higher than that in microsatellite stable patients [(32.40±14.90)%, P=0.003]. The Poly-G mutation frequency was not correlated with age, gender, and pathological staging (all P>0.05). Based on Poly-G genotype difference of the paired samples, the phylogenetic trees of 20 patients were constructed, showing the evolution process of the tumor, especially the subclonal origins of lymph node metastasis. Conclusion: Poly-G mutations accumulate in the occurrence and development of CRC, and can be used as genetic markers to generate reliable maps of intratumor heterogeneity in large numbers of patients with minimal time and cost expenditure.

Risk factors of transfusion-related circulating overload in inpatients and their relationship with clinical outcome / 中国输血杂志

【Objective】 To investigate the risk factors of transfusion-related circulating overload (TACO) in hospitalized patients and to analyze its impact on clinical outcome. 【Methods】 The clinical data of 295 patients with blood transfusion admitted to our hospital from June 2020 to June 2022 were retrospectively analyzed. The patients were divided into TACO group (n=23) and control group (n=272) according to the incidence of TACO. The risk factors of TACO were analyzed by Logistic regression, and the differences of hospital stay and mortality between the TACO group and the control group were compared. 【Results】 TACO occurred in 23 of 295 patients, accounting for 7.80% of all transfusion reactions. The incidence of TACO in different transfusion components was different. Elder age, history of heart failure, history of chronic kidney disease, large mean blood transfusion volume, positive fluid balance [OR(95%CI)): 2.022 (1.212-3.372), 1.917(1.258-2.922), 1.719 (1.155-2.560), 2.252 (1.256- 4.039), 2.221 (1.358-3.633)] were the main risk factors for TACO (P<0.05). 【Conclusion】 Elder age, history of heart failure, history of chronic kidney disease, large blood transfusion volume and positive fluid balance were risk factors for TACO, and TACO was associated with increased length of stay and mortality during hospitalization.

pH and GSH dual-responsive silybin nano-micelles for inhibition of breast cancer activity and metastasis in vitro / 药学学报

The clinical tumor therapy was greatly challenged due to the complex characteristics of tumor microenvironment, however, which also provide arena for novel therapeutic strategies. In this study, poly(2-ethyl-2-oxazoline)-poly(lactic acid)-SS-poly(β-amino ester (PEOz-PLA-SS-PBAE) triblock copolymers with pH and GSH double response were synthesized, polymer micelles were prepared by thin film hydration method for loading of silybin to improve its antitumor activity. The critical micelle concentration was determined by pyrene fluorescence method as 1.8 μg·mL-1. The particle size was 155.30 ± 1.80 nm as determined by dynamic light scattering, with polydispersity index of 0.168 ± 0.004. The drug loading and entrapment efficiency of the micelles were determined by HPLC as (5.48 ± 0.04)% and (68.52 ± 0.48)%, respectively. The in vitro drug release profiles showed that the micelles have low pH sensitivity and high GSH responsiveness, and exhibited sustained release profiles. The good biocompatibility of the material was proved by measuring the hemolysis rate and cytotoxicity of the blank micelle. The cytotoxicity and apoptosis rate of tumor cells showed that the drug loaded PEOz-PLA-SS-PBAE micelles had significant inhibitory effect and apoptosis-inducing effect on MDA-MB-231 cells. The results of wounding healing assay and Transwell invasion test showed that the drug loaded PEOz-PLA-SS-PBAE micelles could significantly inhibit the metastasis of MDA-MB-231 cells. The PEOz-PLA-SS-PBAE drug-loaded micelles prepared in this study have good inhibitory effect on tumor growth and anti-tumor metastasis in vitro, which lays the foundation for the further application of silybin.

Effects of KCNQ1OT1 Gene Knockout Combined with Bruceine D on Proliferation, Migration, and Invasion of Breast Cancer MDA-MB-231 Cells / 肿瘤防治研究

Objective To explore the effect of KCNQ1OT1 gene knockout combined with bruceine D on the proliferation, migration, and invasion of breast cancer MDA-MB-231 cells. Methods Cell Counting Kit-8, wound healing, and Transwell invasion assay were used to detect the effects of bruceine D and siKCNQ1OT1 on the viability, migration, and invasion of MDA-MB-231 cells. Effect of bruceine D and siKCNQ1OT1 on the expression of KCNQ1OT1 in MDA-MB-231 cells was detected by qRT-PCR. Western blot was used to detect the effect of bruceine D and siKCNQ1OT1 on the expression of EMT-related proteins and CDC42, p-MKK7, MKK7 proteins in MDA-MB-231 cells. Results Bruceine D and siKCNQ1OT1 could significantly inhibit the viability, migration, and invasion of MDA-MB-231 cells, and the inhibitory effect was enhanced when they were combined (all P < 0.05); bruceine D downregulated the expression of KCNQ1OT1 in MDA-MB-231 cells (all P < 0.05); bruceine D combined with siKCNQ1OT1 significantly decreased CDC42, p-MKK7, N-cadherin, and Vimentin expression in MDA-MB-231 cells and increased the expression of E-cadherin (all P < 0.05). Conclusion Bruceine D combined with siKCNQ1OT1 significantly inhibit the proliferation, migration, invasion, and EMT of human breast cancer MDA-MB-231 cells, and its molecular mechanism may be related to the blocking of CDC42/MKK7 signaling pathway.

Femtosecond laser assisted phacoemulsification combined with anterior vitrectomy for the treatment of pediatric cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical outcomes of femtosecond laser-assisted cataract phacoemulsification combined with anterior vitrectomy in the treatment of pediatric cataracts.METHODS: Retrospective study. A total of 10 patients(17 eyes)diagnosed as pediatric cataract in Foshan Aier Eye Hospital from January 2021 to September 2022 were collected, including 5 males(9 eyes)and 5 females(8 eyes), with an age of 3～9(4.50±1.20)years old. All children underwent femtosecond laser assisted phacoemulsification combined with anterior vitrectomy. The visual acuity, intraocular pressure and pigment deposits of intraocular lens(IOL)surface, synechia and hyperplasia of posterior capsule lens at 1wk, 1 and 6mo postoperatively were observed during the 6mo follow-up.RESULTS: All surgical procedures were successful, and there was no serious complication intraoperatively or postoperatively. BCVA(LogMAR)was 0.63±0.18 preoperatively and 0.42±0.10, 0.32±0.09, and 0.22±0.08 at 1wk, 1 and 6mo postoperatively(all P&#x003C;0.001). There was no difference in the comparison of intraocular pressure at different times of surgery(P=0.125). There was no statistically significant difference in the incidence of IOL surface pigment deposits, synechia, and posterior capsule lens hyperplasia at different times after surgery(P&#x003E;0.05). The incidence of IOL surface pigment deposits at 1wk, 1 and 6mo after surgery was 3 eyes(18%), 1 eye(6%), and 1 eye(6%), respectively, the incidence of synechia was 0 eye, 1 eye(6%), 2 eyes(12%), and the incidence of posterior capsule lens hyperplasia was 0 eye, 0 eye, and 2 eyes(12%), respectively.CONCLUSION: Femtosecond laser-assisted cataract phacoemulsification combined with vitrectomy for the removal of the anterior vitreous can effectively prevent anterior capsular tear and the occurrence of posterior capsule opacification.

Practice of structured electronic medical record design and quality management / 中华医院管理杂志

In order to assist in the standardization and maturity evaluation of national hospital information interconnection, and further standardize the application and management of hospital medical record data, a hospital carried out the practice of design of structured medical records and the corresponding quality management from April 2021. Based on the six sigma quality management method, the hospital had developed universal templates for electronic medical records and a list of candidate electronic medical record templates. The problems faced by medical record data had been analyzed, and improvement strategies had been proposed from three levels: template design, software functionality and management services. The clinical departments were guided to design and develop various structured electronic medical record templates for specialties and specialized diseases, and established a medical record template design and quality management method. The hospital had ultimately designed a total of 614 structured electronic medical record templates that met the actual needs of the hospital. This practice enhanced the scalability of structured templates and quality of the data, and achieved localization and specialization of medical record templates while meeting the requirements of information interconnection and sharing, providing reference for promoting the interconnection and sharing of electronic medical records of hospitals in China.

A retrospective study correlating the prognoses and hospitalization costs of stroke survivors with dysphagia / 中华物理医学与康复杂志

Objective:To seek any correlation between and prognosis and hospitalization costs of stroke survivors with dysphagia.Methods:The records of 1370 stroke survivors admitted to the rehabilitation departments of 3 public hospitals in Weifang were studied. Of them, 499 (36.4%) were diagnosed with dysphagia and 871 were not. Binary logistic regression and multiple linear regression were employed to analyze the correlation between dysphagia and the occurrence of pneumonia, modified Rankin Scale (mRS) scores, modified Barthel index (MBI) scores, length of stay and total hospitalization cost.Results:After adjusting for confounding factors, the risk of pneumonia in the dysphagia group was 2.4 times higher. At discharge, the risk of an mRS≥3 was 3.3 times greater and that of an MBI score <60 was 1.7 times greater with dysphagia. Multiple stepwise linear regression showed that dysphagia was significantly associated with higher mRS scores at discharge, lower MBI scores, and longer hospital stays. The standardized regression coefficients predict that after the length of stay, dysphagia is the strongest predictor of the cost of hospitalisation, followed by ADL ability, pneumonia, supratentorial, haemorrhagic stroke and CCI.Conclusions:Dysphagia is a significant predictor of the hospitalization costs of stroke patients. It is recommended to identify and treat dysphagia as early as possible to improve the prognosis of such patients and reduce the economic burden.

Effect of "Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion on the expression of Fas/FADD/Caspase-8 of death receptor pathway in rats with primary ovarian insufficiency / 中国针灸

OBJECTIVE@#To explore the effect of "Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion on the ovarian function in the rats with primary ovarian insufficiency (POI) and the potential effect mechanism based on the Fas/FADD/Caspase-8 of death receptor pathway.@*METHODS@#Forty-eight female SD rats were randomly divided into a blank group, a model group, a medication group and an acupuncture group, with 12 rats in each group. Except in the blank group, the rats in the other groups were intraperitoneally injected with cyclophosphamide to establish the POI model. In the acupuncture group, after successful modeling, the intervention was given with "Zhibian" (BL 54)-to- "Shuidao" (ST 28) needle insertion, once daily, 30 min in each intervention; and the duration of intervention was 4 weeks. In the medication group, estradiol valerate tablets were administered intragastrically, 0.09 mg•kg-1•d-1, for 4 weeks. The general situation and the estrous cycle of the rats were compared among groups. Using ELISA, the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) in the serum were detected. HE staining was adopted to observe the morphological changes of ovarian tissue of rats. The protein expression of Fas, FADD and Caspase-8 in ovarian tissue was detected with immunohistochemistry and Western blot.@*RESULTS@#After modeling, except the rats of the blank group, the rats of the other groups had dry fur, lost hair, low spirits, reduced food intake, increased urination and loose stool. After intervention, the stool became regular gradually in the acupuncture group and the medication group. The percentage of estrous cycle disturbance was increased in the rats of the model group when compared with the blank group (P<0.01); in comparison with the model group, the percentages of estrous cycle disturbance were reduced in the acupuncture group and the medication group after intervention (P<0.01). When compared with the blank group, the body mass and E2 content in the serum were lower (P<0.01), the levels of FSH and LH in the serum and the protein expression levels of Fas, FADD and Caspase-8 were increased (P<0.01) in the model group. Compared with the model group, the body mass and E2 contents in the serum were higher (P<0.01), the levels of FSH and LH in the serum and the protein expression levels of Fas, FADD and Caspase-8 were reduced (P<0.01) in the acupuncture group and the medication group.@*CONCLUSION@#"Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion can effectively improve the ovarian function of POI rats, and its effect mechanism may be related to regulating the serum sex hormone levels, reducing the expression of Fas, FADD and Caspase-8 in ovarian tissue and retarding apoptosis of ovarian cells.

Effect of acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) on the expression of apoptosis-related factors in rats with premature ovarian insufficiency based on oxidative stress / 中国针灸

OBJECTIVE@#To explore the possible mechanism of acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) on premature ovarian insufficiency (POI) from the perspective of oxidative stress.@*METHODS@#Sixty female SD rats were randomly divided into a blank group, a model group, a sham acupuncture group, a medication group, and an acupuncture group, 12 rats in each group. Except the blank group, the rats in the remaining groups were intraperitoneally injected with cyclophosphamide to establish the POI model. After the model was successfully established, the rats in the acupuncture group were treated with acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28), with a depth of about 12 mm, and the needle was retained for 30 min; the acupuncture was given once a day, for a total of 4 weeks. The rats in the sham acupuncture group were treated with blunt-head needle to tap the skin surface of "Zhibian" (BL 54), without penetrating the skin, once a day for 4 weeks. The rats in the medication group were treated with estradiol valerate by gastric gavage for 4 weeks. After the intervention, the level of reactive oxygen species (ROS) in the ovarian tissue was detected by fluorescence probe; the expression of c-Jun N-terminal kinase (JNK), forkhead box O1 (FoxO1), tumor suppressor gene protein 53 (p53) and p53 up-regulated modulator of apoptosis (Puma) mRNA and protein in ovarian tissue were detected by real-time fluorescence quantitative PCR and Western blot.@*RESULTS@#Compared with the blank group, the level of ROS and the expression of JNK mRNA, p-JNK protein, FoxO1, p53, Puma mRNA and protein in the ovarian tissue in the model group were increased (P<0.01). Compared with the model group, the level of ROS and the expression of p-JNK protein, FoxO1, p53, Puma mRNA and protein in the ovarian tissue in the sham acupuncture group were slightly reduced, but the difference was not statistically significant (P>0.05). The level of ROS and the expression of JNK mRNA, p-JNK protein, FoxO1, p53, Puma mRNA and protein in the ovarian tissue in the acupuncture group and the medication group were reduced (P<0.01).@*CONCLUSION@#Acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) could improve the level of oxidative stress, down-regulate the expression of apoptosis-related factors JNK, FoxO1, p53 and Puma induced by oxidative stress, and inhibit the premature failure of ovarian reserve function caused by apoptosis of ovarian granulosa cells in POI rats.

Anti-tumor Mechanisms of Bruceine D： A Review / 中国实验方剂学杂志

Malignant tumors seriously threaten human life and health. Radiotherapy and chemotherapy are the conventional methods for the clinical treatment of advanced tumors. The prognosis and efficacy are still far from satisfactory due to the radiotherapy has serious adverse effects on the body and the chemotherapy often causes problems such as tumor resistance and cell proliferationinhibition. Therefore， the search for new， safe， and effective anti-tumor drugs and the elucidation of their molecular mechanisms are effective measures for clinical treatment of tumors and improvement of patients' quality of life. Active ingredients derived from Chinese herbal medicines and natural products have gradually become a hot spot in the research and development of anti-tumor drugs due to their multi-target and multi-channel anti-tumor pharmacological activity characteristics and their advantages such as less adverse reaction on the body. Bruceine D is a class of tetracyclic triterpenoids extracted from the fruit of the Chinese herbal medicine Bruceae Fructus， with anti-inflammatory， anti-malarial， anti-parasitic， and other pharmacological activities， and its anti-tumor activity is particularly significant. Pharmacological studies have found that bruceine D can regulate various cellular physiological activities such as proliferation， apoptosis， invasion， and migration of lung cancer， liver cancer， pancreatic cancer， intestinal cancer， and other cancer cells by targeting different signaling pathways. Bruceine D can be used in combination with other chemotherapeutic drugs to improve the sensitivity of tumor cells to chemotherapeutic drugs， thereby reducing the adverse effect of chemotherapy. Clinical application practice has shown that Bruceae Fructus oil emulsion injection containing bruceine D has significant advantages in the efficacy and safety of tumor treatment. Although there are many studies on the antitumor pharmacological activity of bruceine D and its clinical efficacy is significant， the specific antitumor molecular mechanism of bruceine D is still unclear， and there is a lack of systematic review on the existing antitumor mechanism of bruceine D. Therefore， based on the research on bruceine D in China and abroad in recent years， this paper reviewed the anti-tumor effect and related molecular mechanisms of bruceine D from six aspects， namely， tumor cell proliferation， apoptosis， metastasis and invasion， glucose metabolism process， autophagy， and chemotherapy sensitivity. This paper is expected to provide a pharmacological basis and scientific reference for the antitumor drug development and clinical application of bruceine D.

Preparation，characterization，in vitro drug release property and cytotoxicity of Periplaneta americana extract-loaded spider fibroin membrane / 中国药房

OBJECTIVE To prepare spider fibroin membrane loaded with Periplaneta americana extract， and investigate its characterization， in vitro drug release property and cytotoxicity. METHODS Using natural spider silk collected from Chilobrachys guangxiensis as raw material， P. americana extract as model drug， the drug-loaded spider fibroin membrane （hereinafter referred to as drug-loaded membrane） was prepared by solvent casting method. The material matrix spider fibroin membrane without P. americana extract （hereinafter referred to as blank membrane） was prepared with same method. The membrane structure was characterized by static water contact angle， Fourier infrared chromatography， X-ray diffraction and scanning electron microscopy from different angles； drug release characteristics in artificial saliva were simulated in vitro to evaluate the drug sustained-release performance. MTT assay was adopted to validate the cytotoxicity of drug-loaded membrane. RESULTS The drug-loaded membrane was prepared， and the static water contact angle was less than 90°， which was less than that of blank membrane. The drug-loaded membrane showed the characteristic absorption peak to polypeptide of P. americana extract at 1 500-1 700 cm－1. X-ray diffraction and scanning electron microscopy also proved that the drug was successfully loaded into the pellicle. The release time of the pellicle in artificial saliva was more than 200 min. The MTT test results showed that the cell proliferation rates of blank membrane and drug-loaded membrane were 84.6% and 79.4% （both greater than 70%）， respectively， without significant potential cytotoxicity. CONCLUSIONS Drug-loaded membrane prepared with natural spider silk has a certain sustained-release effect in artificial saliva， which can be further developed as a drug sustained-release carrier with excellent biological characteristics and biocompatibility.

Status and Prospect of Management Policy and System for High-level Pathogenic Microorganism Laboratories in China / 中山大学学报(医学科学版)

High-level pathogenic microorganism laboratories are strategic scientific and technological forces of national biosafety， so it is significant to improve the policy and system management and strengthen the safety supervision. This paper reviewed the current status of management policy and system of high-level pathogenic microorganism laboratories， summarized the problems and challenges in terms of safety laws and regulations， supervision mechanism， hierarchical and classified management， standards and norms， legal person responsibility system， occupational access system and personnel training system. This paper also proposed targeted policy suggestions that might underlie the biosafety management of high-level pathogenic microorganism laboratories in China.

Outcome analysis of pregnancy termination and expectant treatment in pregnant women with suspected invasive placenta accreta spectrum disorders in the second trimester / 中华妇产科杂志

Objective: To investigate the maternal and fetal outcomes of expectant treatment and early termination of pregnancy in pregnant women with suspected invasive placenta accreta spectrum disorders (PAS) in the second trimester. Methods: A retrospective cohort study was performed on 51 pregnant women with suspected invasive PAS (ultrasound score ≥10) evaluated by ultrasound with gestational age <26 weeks and confirmed as invasive PAS by intraoperative findings or postoperative pathology in Peking University Third Hospital from January 2015 to January 2022. According to the informed choice of pregnant women and their families, they were divided into expectant treatment group (37 cases) and mid-term termination group (14 cases). The general clinical data and outcome indexes of the two groups were analyzed by χ2 test, Mann-Whitney U rank sum test, logistic regression and linear regression. Results: (1) General clinical data: among 51 pregnant women who were assessed as suspected invasive PAS by ultrasonography in the second trimester, invasive PAS was finally diagnosed by intraoperative findings and postoperative pathology, among which 46 cases (90%) were placenta percreta and 5 cases (10%) were placenta increta. (2) Outcome indicators: univariate analysis showed that there were no statistically significant differences in the intraoperative blood loss (median: 2 200 vs 2 150 ml), the proportion of blood loss >1 500 ml [73% (27/37) vs 9/14], the hysterectomy rate [62% (23/37) vs 8/14], the rate of intensive care unit (ICU) admission [78% (29/37) vs 9/14] between the expectant treatment group and the mid-term termination group (all P>0.05). Multivariate analysis showed that the rate of intraoperative blood loss >1 500 ml (aOR=0.481, 95%CI: 0.017-13.958; P=0.670), hysterectomy (aOR=0.264, 95%CI: 0.011-6.569, P=0.417) and ICU admission (aOR=1.327, 95%CI: 0.048-36.882, P=0.867) between the two groups showed no statistical differences. (3) Outcome analysis: all 37 cases in the expectant treatment group had live births and no early neonatal death. Five pregnant women (14%, 5/37) in the expectant treatment group underwent emergency cesarean section in the course of expectant treatment. In the mid-term termination group, all pregnancies were terminated by operation, including 9 cases of hysterectomy and 5 cases of placental hysterectomy. There was 1 fetal survival (gestational age of termination: 27+4 weeks) and 13 fetal death in the mid-term termination group. Conclusions: Pregnant women who are diagnosed as suspected invasive PAS, especially those with placenta percreta, have the risk of uterine rupture and emergency surgery in the course of expectant treatment. However, early termination of pregnancy does not reduce the risk of intraoperative blood loss and hysterectomy.

A risk prediction model of cervical cancer developed based on nested case-control design / 中华流行病学杂志

Objective: To construct a cervical cancer risk prediction model based on nested case-control study design and Yinzhou Health Information Platform in Ningbo, and provide reliable reference for self-risk assessment of cervical cancer in local women. Methods: In local women aged 25-75 years old who had no history of cervical cancer registered in Yinzhou before October 31, 2018, a follow up was conducted for at least three years, the patients who developed cervical cancer during the follow up period were selected as the case group and matched with a control group at a ratio of 1∶10. The prediction indicators before the onset was used in model construction. Variables were selected by Lasso-logistic regression, the variables with non-zero β were selected to fit the logistic regression model and Bootstrap was used for internal validation. The discrimination of the model was evaluated by area under the receiver operating characteristic curve(AUROC), and the calibration was evaluated by calibration curve and Hosmer-Lemeshow test. Results: The prediction indicators included in the final model were age, smoking status, history of cervicitis, history of adenomyosis, HPV testing, and thinprep cytologic test. The AUROC calculated in the internal validation was 0.740 (95%CI:0.739-0.740), and the calibration curve was almost identical with the ideal curve, P=0.991 in Hosmer-Lemeshow test, indicating that the model discrimination and calibration were good. Conclusions: In this study, a simple and practical cervical cancer risk prediction model was developed. The model can be used in general population with strong interpretability, good discrimination and calibration in internal validation, which can provide a reference for women to assess their risk of cervical cancer.

CHD1 deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer / 亚洲男科学杂志(英文版)

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.

Analysis on health status and influencing factors of 1353 mercury workers in Xinjiang / 中华劳动卫生职业病杂志

Objective: To investigate the health status of workers exposed to occupational mercury, and to provide the theoretical basis for formulating reasonable health monitoring and targeted protection measures. Methods: In November 2021, 1353 mercury-exposed workers who underwent occupational health examination in a hospital in Xinjiang Uygur Autonomous Region from 2018 to 2021 were collected as research subjects. By analyzing their blood pressure, electrocardiogram, blood routine, liver function and urine β2-microglobulin and urinary mercury in different gender, age, length of service, industry and enterprise scale, and the health status. And the influencing factors of urinary mercury were evaluated. Results: Among 1353 workers exposed to mercury, there were 1002 males (74.1%), the average age was (37.2±9.8) years old, and the length of service was 3.1 (2.0, 8.0) years. The abnormal rates of physical examination, blood pressure, electrocardiogram, blood routine, liver function, urinary β2-microglobulin and urinary mercury were 73.9% (1000/1353), 12.3% (166/1353), 30.2% (408/1353), 59.9% (810/1353), 32.5% (440/1353), 15.2% (205/1353) and 2.2% (30/1353), respectively. The abnormal rates of blood pressure, blood routine, liver function, urinary β2-microglobulin and urinary mercury in male workers were higher than those in female workers (P<0.05). The abnormal rates of workers' blood pressure and physical examination results increased with the increase of age and length of service, while the abnormal rate of electrocardiogram results were opposite (P<0.05). There were statistically significant differences in the abnormal rates of blood pressure, blood routine, urinary β2-microglobulin and physical examination results among workers of different enterprises and different industries (P<0.05). Multivariate logistic regression analysis showed that the workers with age ≥30 years old, microminiature enterprises, abnormal physical examination results and urinary β2-microglobulin were the susceptible population with abnormal urinary mercury (P<0.05) . Conclusion: The occupational health status of mercury workers in Xinjiang Uygur Autonomous Region is not optimistic, and the health monitoring of microminiature enterprises and older workers should be improved to effectively protect the physical and mental health of workers.

Systematic comparison of two kinds of Bufonis Venenum derived from different Bufo gargarizans subspecies based on metabolomics and antitumor activity / 中国中药杂志

This paper compared the differences between two kinds of Bufonis Venenum produced by Bufo gargarizans gargarizans and B. gararizans andrewsi, and verified the rationality of the market value orientation of Bufonis Venenum based on the zebrafish mo-del. Twenty batches of Bufonis Venenum from Jiangsu province, Hebei province, Liaoning province, Jilin province, and Liangshan, Sichuan province, including B. gargarizans gargarizans and B. gararizans andrewsi, were collected. The UHPLC-LTQ-Orbitrap-MS combined with principal component analysis was used to compare the differences between two kinds of Bufonis Venenum. According to the limiting conditions of VIP>1, FC<0.5 or FC>2.0, and peak total area ratio>1%, 9 differential markers were determined, which were cinobufagin, cinobufotalin, arenobufagin, resibufogenin, scillaredin A, resibufagin, 3-(N-suberoylargininyl)-arenobufagin, 3-(N-suberoylargininyl)-marinobufagin, and 3-(N-suberoylargininyl)-resibufogenin. The content of 20 batches of Bufonis Venenum was determined according to the Chinese Pharmacopoeia(2020 edition) by high-performance liquid chromatography, and the 2 batches of Bufonis Venenum, CS7(8.99% of total content) and CS9(5.03% of total content), with the largest difference in the total content of the three quality control indexes of the Chinese Pharmacopoeia(bufalin, cinobufagin, and resibufogenin) were selected to evaluate their anti-liver tumor activity based on the zebrafish model. The tumor inhibition rates of the 2 batches were 38.06% and 45.29%, respectively, proving that only using the quality control indexes of the Chinese Pharmacopoeia as the value orientation of Bufonis Venenum market circulation was unreasonable. This research provides data support for the effective utilization of Bufonis Venenum resources and the establishment of a rational quality evaluation system of Bufonis Venenum.

Clinical application value of Huanglian Jiedu Pills in improving syndrome of excess heat and fire toxin based on phase Ⅱ clinical trial study on plasma ATP, 4-HNE, and ACTH levels / 中国中药杂志

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.

Content analysis and quality evaluation of main active components and mineral elements of Cynomorium songaricum in different habitats / 中国中药杂志

To clarify the content characteristics of the main active components and mineral elements of Cynomorium songaricum under different habitat conditions, and further explore the relationship between the quality of C. songaricum and habitats, this study took C. songaricum from 25 different habitats in China as the research object, and measured the contents of 8 main active components and 12 mineral elements separately. Diversity analysis, correlation analysis, principal component analysis and cluster analysis were carried out. The results showed that the genetic diversity of total flavonoids, ursolic acid, ether extract, potassium(K), phosphorus(P) and zinc(Zn) in C. songaricum was high. The coefficient of variation of crude polysaccharide, ether extract, gallic acid, protocatechuic aldehyde, catechin, epicatechin, calcium(Ca), sodium(Na), magnesium(Mg), sulfur(S), iron(Fe), manganese(Mn), selenium(Se) and nickel(Ni) were all over 36%, indicating that the quality of C. songaricum was significantly affected by habitats. There were strong synergistic and weak antagonistic effects among the contents of the 8 active components, and complex antagonistic and synergistic effects among the contents of the 12 mineral elements. Principal component analysis revealed that crude polysaccharide, ursolic acid, catechin, epicatechin and total flavonoids could be used as the characteristic components to evaluate the quality of C. songaricum, and Na, copper(Cu), Mn and Ni were the characteristic elements to evaluate the quality of C. songaricum. In cluster ana-lysis, the second group with the main active components as cluster center had better quality in terms of the content of active substances, and the second group with the mineral elements as cluster center had higher utilization potential in the exploitation of mineral elements. This study could provide a basis for resource evaluation and breeding of excellent varieties of C. songaricum in different habitats, and provide a reference for cultivation and identification of C. songaricum.

Mechanism of Xiaoer Chiqiao Qingre Granules in clearing heat and removing food stagnation in suckling rats with fever and food accumulation based on metabolomics / 中国中药杂志

Children's fever is often accompanied by food accumulation. Traditional Chinese medicine believes that removing food stagnation while clearing heat of children can effectively avoid heat damage. To systematically evaluate the efficacy of Xiaoer Chiqiao Qingre Granules(XRCQ) in clearing heat and removing food accumulation and explore its potential mechanism, this study combined suckling SD rats fed with high-sugar and high-fat diet with injection of carrageenan to induce rat model of fever and food accumulation. This study provided references for the study on the pharmacodynamics and mechanism of XRCQ. The results showed that XRCQ effectively reduced the rectal temperature of suckling rats, improved the inflammatory environment such as the content of interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ(IFN-γ), white blood cells, and monocytes. XRCQ also effectively repaired intestinal injury and enhanced intestinal propulsion function. According to the confirmation of its efficacy of clearing heat, the thermolytic mechanism of XRCQ was further explored by non-targeted and targeted metabolomics methods based on LTQ-Orbitrap MS/MS and UPLC-QQQ-MS/MS. Non-target metabolomics analysis of brain tissue samples was performed by QI software combined with SIMCA-P software, and 22 endogenous metabolites that could be significantly regulated were screened out. MetaboAnalyst pathway enrichment results showed that the intervention mechanism was mainly focused on tyrosine metabolism, tricarboxylic acid cycle, inositol phosphate metabolism, and other pathways. At the same time, the results of targeted metabolomics of brain tissue samples showed that XRCQ changed the vitality of digestive system, and inhibited abnormal energy metabolism and inflammatory response, playing a role in clearing heat and removing food stagnation from multiple levels.