Targeting microRNA-125b inhibited the metastasis of Alisertib resistance cells through mediating p53 pathway / 中华肿瘤杂志

Objective: To clarify the mechanisms involvement in Alisertib-resistant colorectal cells and explore a potential target to overcome Alisertib-resistance. Methods: Drug-resistant colon cancer cell line (named as HCT-8-7T cells) was established and transplanted into immunodeficient mice. The metastasis in vivo were observed. Proliferation and migration of HCT-8-7T cells and their parental cells were assessed by colony formation and Transwell assay, respectively. Glycolytic capacity and glutamine metabolism of cells were analyzed by metabolism assays. The protein and mRNA levels of critical factors which are involved in mediating glycolysis and epithelial-mesenchymal transition (EMT) were examined by western blot and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR), respectively. Results: In comparison with the mice transplanted with HCT-8 cells, which were survival with limited metastatic tumor cells in organs, aggressive metastases were observed in liver, lung, kidney and ovary of HCT-8-7T transplanted mice (P<0.05). The levels of ATP [(0.10±0.01) mmol/L], glycolysis [(81.77±8.21) mpH/min] and the capacity of glycolysis [(55.50±3.48) mpH/min] in HCT-8-7T cells were higher than those of HCT-8 cells [(0.04±0.01) mmol/L, (27.77±2.55) mpH/min and(14.00±1.19) mpH/min, respectively, P<0.05]. Meanwhile, the levels of p53 protein and mRNA in HCT-8-7T cells were potently decreased as compared to that in HCT-8 cells (P<0.05). However, the level of miRNA-125b (2.21±0.12) in HCT-8-7T cells was significantly elevated as compared to that in HCT-8 cells (1.00±0.00, P<0.001). In HCT-8-7T cells, forced-expression of p53 reduced the colon number (162.00±24.00) and the migration [(18.53±5.67)%] as compared with those in cells transfected with control vector [274.70±40.50 and (100.00±29.06)%, P<0.05, respectively]. Similarly, miR-125b mimic decreased the glycolysis [(25.28±9.51) mpH/min] in HCT-8-7T cells as compared with that [(54.38±12.70)mpH/min, P=0.003] in HCT-8-7T cells transfected with control. Meanwhile, in comparison with control transfected HCT-8-7T cells, miR-125b mimic also significantly led to an increase in the levels of p53 and β-catenin, in parallel with a decrease in the levels of PFK1 and HK1 in HCT-8-7T cells (P<0.05). Conclusions: Silencing of p53 by miR-125b could be one of the mechanisms that contributes to Alisertib resistance. Targeting miR-125b could be a strategy to overcome Alisertib resistance.

Analysis on missed diagnosis or misdiagnosis of anomalous origin of left coronary artery from pulmonary artery by echocardiography from one single medical center / 中华心血管病杂志

Objectives: To analyze the reasons of missed diagnosis or misdiagnosis on anomalous origin of left coronary artery from pulmonary artery (ALCAPA) by echocardiography. Methods: This is a retrospective study. Patients with ALCAPA who underwent surgical treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from August 2008 to December 2021 were included. According to the results of preoperative echocardiography and surgical diagnosis, the patients were divided into confirmed group or missed diagnosis/misdiagnosis group. The results of preoperative echocardiography were collected, and the specific echocardiographic signs were analyzed. According to the experience of the doctors, the echocardiographic signs were divided into four types, namely clear displayed, vague/doubtful displayed, no display and no notice, and the display rate of each sign was calculated (display rate=number of clearly displayed cases/total number of cases×100%). By referring the surgical data, we analyzed and recorded the pathological anatomy and pathophysiological characteristics of the patients, and the rate of missed diagnosis/misdiagnosis of echocardiography in patients with different characteristics was compared. Results: A total of 21 patients were enrolled, including 11 males, aged 1.8 (0.8, 12.3) years (range 1 month to 47 years). Except for one patient with anomalous origin of left anterior descending artery, the others were all originated from the main left coronary artery (LCA). There were 13 cases of ALCAPA in infant and children, and 8 cases of adult ALCAPA. There were 15 cases in the confirmed group (diagnostic accuracy was 71.4% (15/21)), and 6 cases in the missed diagnosis/misdiagnosis group (three cases were misdiagnosed as primary endocardial fibroelastosis, two cases were misdiagnosed as coronary-pulmonary artery fistula; and one case was missed diagnosis). The working years of the physicians in the confirmed group were longer than those in the missed diagnosis/misdiagnosed group ((12.8±5.6) years vs. (8.3±4.7) years, P=0.045). In infants with ALCAPA, the detection rate of LCA-pulmonary shunt (8/10 vs. 0, P=0.035) and coronary collateral circulation (7/10 vs. 0, P=0.042) in confirmed group was higher than that in missed diagnosis/misdiagnosed group. In adult ALCAPA patients, the detection rate of LCA-pulmonary artery shunt was higher in confirmed group than that in missed diagnosis/misdiagnosed group (4/5 vs. 0, P=0.021). The missed diagnosis/misdiagnosis rate of adult type was higher than that of infant type (3/8 vs. 3/13, P=0.410). The rate of missed diagnosis/misdiagnosis was higher in patients with abnormal origin of branches than that of abnormal origin of main trunk (1/1 vs. 5/21, P=0.028). The rate of missed diagnosis/misdiagnosis in patients with LCA running between the main and pulmonary arteries was higher than that distant from the main pulmonary artery septum (4/7 vs. 2/14, P=0.064). The rate of missed diagnosis/misdiagnosis in patients with severe pulmonary hypertension was higher than that in patients without severe pulmonary hypertension (2/3 vs. 4/18, P=0.184). The reasons with an echocardiography missed diagnosis/misdiagnosis rate of≥50% included that (1) the proximal segment of LCA ran between the main and pulmonary arteries; (2) abnormal opening of LCA at the right posterior part of the pulmonary artery; (3) abnormal origin of LCA branches; (4) complicated with severe pulmonary hypertension. Conclusions: Echocardiography physicians' knowledge of ALCAPA and diagnostic vigilance are critical to the accuracy of diagnosis. Attention should be paid to the pediatric cases with no obvious precipitating factors of left ventricular enlargement, regardless of whether the left ventricular function is normal or not, the origin of coronary artery should be routinely explored.

Comparison of long-term clinical outcomes between transvaginal mesh and pelvic floor reconstruction with native tissue repair in the treatment of advanced pelvic organ prolapse / 中华妇产科杂志

Objective:To study the long-term clinical effect of transvaginal mesh (TVM) and pelvic floor reconstruction with native tissue repair (NTR) in the treatment of advanced pelvic organ prolapse (POP).Methods:Totally 207 patients with advanced POP who were treated in Hunan Provincial Maternal and Child Health Care Hospital from Jan. 2016 to Sep. 2019 were enrolled. The patient′s pelvic organ prolapse quantification were all at degree Ⅲ or above, and they all complained for different degree of symptoms. They were divided into two groups according to the different surgical methods, TVM group and NTR group. In TVM group, the mesh was implanted through the vagina for pelvic floor reconstruction, while in NTR group, the traditional transvaginal hysterectomy combined with uterosacral ligament suspension and anterior and posterior wall repair, as well as perineal body repair were performed. The median follow-up time was 60 months, during the follow up time, 164 cases (79.2%, 164/207) had completed follow-up, including 76 cases in TVM group and 88 cases in NTR group. The perioperative data and complication rates of the two groups were compared, and the subjective and objective outcomes of the two groups at 1, 3 and 5 years were observed, respectively. The objective efficacy was evaluated by three composite criteria, namely: (1) the distance from the farthest end of the prolapse of the anterior and posterior wall of the vagina to the hymen is ≤0 cm, and the descending distance of the top is ≤1/2 of the total length of the vagina; (2) determine the disappearance of relevant POP symptoms according to “Do you often see or feel vaginal mass prolapse？”; (3) no further operation or pessary treatment was performed due to prolapse. If the above three criteria were met at the same time, the operation is successful; otherwise, it was recurrence. The subjective efficacy was evaluated by the pelvic floor distress inventory-short form 20 (PFDI-20) and pelvic floor impact questionnaire-short form 7 (PFIQ-7).Results:The median follow-up time of the two groups was 60 months (range: 41-82 months). Five years after the operation, the subjective and objective cure rates of TVM group were 89.5% (68/76) and 94.7% (72/76), respectively. The subjective and objective cure rates in NTR group were 80.7% (71/88) and 85.2% (75/88), respectively. There were significant differences in the subjective and objective cure rates between the two groups ( χ2=9.869, P=0.002; χ2=3.969, P=0.046). The recurrence rate of TVM group was 5.3% (4/76), and that of NTR group was 14.8% (13/88). There was a significant difference between the two groups ( P=0.046). The postoperative PFDI-20 and PFIQ-7 scores of the two groups were significantly lower than those before surgery, and there were significant differences of the two groups before and after surgery (all P<0.05). Postoperative mesh exposure in TVM group was 1.3% (1/76). Conclusions:The long-term outcomes between the two groups show that the subjective and objective outcomes of pelvic floor reconstruction in TVM group are significantly higher than those in NTR group, and the recurrence rate is significantly lower than that in NTR group. TVM has certain advantages in the treatment of advanced POP.

Correlation between the quartering method of nerve root subsidence sign and the cross-sectional area of the narrow segment thecal sac in patients with lumbar spinal stenosis / 中国医师杂志

Objective:To study the correlation between the quartering of nerve root subsidence sign (NRS) and the cross-sectional area (CSA) of the narrow segment thecal sac in patients with lumbar spinal stenosis (LSS).Methods:The data of 203 LSS patients in the Fourth People′s Hospital of Hengshui from January 2020 to December 2021 were retrospectively analyzed. All patients underwent MRI cross sectional scanning. The patients were divided into positive type a group ( n=62), positive type b group ( n=32), positive type c group ( n=51), and negative group ( n=58) by NRS quartering method. The minimum CSA, median sagittal diameter (PAD), and lateral recess sagittal diameter of each group were compared. The correlation between NRS quartering classification and the minimum CSA and related indicators of lumbar spinal stenosis was analyzed. Results:The minimum CSA, PAD, and sagittal diameter of the lateral recess in the positive a group, positive b group, and positive c group were all smaller than those in the negative group, while the Visual Analogue Scale (VAS) score and Oswestry Disability Index (ODI) were higher than those in the negative group; The minimum CSA, PAD, and sagittal diameter of the lateral recess in the positive b type and positive c type groups were smaller than those in the positive a type group, while the VAS score and ODI index were higher than those in the positive a type group; The minimum CSA, PAD, and sagittal diameter of the lateral recess in the positive c type group were smaller than those in the positive b type group; The VAS score and ODI index were higher than those of the positive b type group; The differences were statistically significant (all P<0.05). 203 patients were divided into 54 normal cases, 58 mild stenosis cases, 49 moderate stenosis cases, and 42 severe stenosis cases based on the minimum CSA. The coincidence rate between negative NRS and minimal CSA diagnosis as normal was 94.44%(51/54), the coincidence rate between positive type a and minimal CSA diagnosis as mild stenosis was 84.48%(49/58), the coincidence rate between positive type b and minimal CSA diagnosis as moderate stenosis was 53.06%(26/49), and the coincidence rate between positive type c and minimal CSA diagnosis as severe stenosis was 90.48%(38/42). Using the kappa consistency test, the kappa value for quantitative diagnosis of minimum CSA stenosis in NRS and LSS patients was 0.743, indicating good consistency. The kappa values for quantitative diagnosis of NRS, sagittal diameter of lateral recess, and PAD stenosis were 0.271 and 0.335, with poor consistency. NRS typing was negatively correlated with CSA and PAD ( r=-0.723, -0.581, all P<0.001), and positively correlated with VAS score and ODI index ( r=0.473, 0.640, all P<0.001). Conclusions:The NRS quartering method has a good consistency in diagnosing the severity of LSS patients and the minimum CSA of stenosis segments, suggesting that the NRS quartering method can better reflect the degree of Spinal stenosis, which can not only be used as an auxiliary indicator for qualitative diagnosis of LSS, but also has a high value in quantitative diagnosis.

Survey on iodine deficiency disorders awareness, education status and willingness of pupils in Guizhou Province / 中华地方病学杂志

Objective:To learn about the awareness, education status and willingness of iodine deficiency disorders (IDD) among elementary school students in Guizhou Province, and to provide a scientific basis for exploring intervention strategies for health education of iodine deficiency in the future.Methods:From June 2021 to May 2022, each IDD monitoring county was selected from the east, south, west, north and middle directions of Guizhou Province, and one elementary school was selected from each county. All students in two classes of Grade 5 and Grade 6 were selected in whole groups to conduct on-site questionnaire surveys in the form of anonymous examinations. The survey mainly included general demographic information and IDD awareness, education status and willingness, and binary logistic regression was used to analyze the relevant influencing factors.Results:A total of 1 259 elementary school students in Guizhou Province were investigated, the rates of awareness of IDD, acceptance of IDD publicity and education, and willingness to accept IDD publicity and education among elementary school students were 37.7% (1 900/5 036), 25.1% (316/1 259) and 69.6% (876/1 259), respectively. By binary logistic regression analysis, gender, residence, grade and father's education level were the influencing factors of pupils' awareness of iodine deficiency ( P < 0.05); residence, age and father's education level were the influential factors of elementary school students receiving iodine deficiency education ( P < 0.05); gender, residence, ethnicity and whether the child was the only child or not were the influential factors of elementary school students' willingness to accept IDD education ( P < 0.05). Conclusions:The elementary school students in Guizhou Province have insufficient knowledge about IDD. The publicity and education for iodine deficiency prevention is limited, and the students' willingness to learn is not high. The publicity, education and intervention for iodine deficiency prevention among elementary school students should be comprehensively strengthened.

Prediction of the disease burden of genital herpes in China in 1990 -2019 / 公共卫生与预防医学

Objective To analyze the current situation and trend of genital herpes disease burden in China from 1990 to 2019, and to provide a theoretical basis for the prevention and treatment of genital herpes. Methods Using the 2019 Global Burden of Disease database, the trend of the burden of genital herpes disease in China from 1990 to 2019 was analyzed using the Joinpoint software based on the indicators of incidence, disability-adjusted life years (DALY) and disability-lost life years. The ARIMA time series model was established to predict the development trend of genital herpes diseases in China from 2020 to 2024. Results From 1990 to 2019, the incidence of genital herpes in China had a downward trend. The incidence of the disease was mainly concentrated in the age group of 15-49 years old, and the DALY rate in this age group showed a significant upward trend (AAPC=0.73, P < 0.001). The age group of 50-69 years old showed a significant upward trend (AAPC=0.09, P < 0.05). The DALY rate of genital herpes in China showed an increasing trend from 1990 to 2019. Between 1990 and 2019, the overall disease burden of women in China was higher than that of men. The ARIMA model predicted that the incidence of genital herpes and DALY rate in China would continue to increase from 2020 to 2024. Conclusion The disease burden of genital herpes in China is still on the rise. It is necessary to strengthen the safe sexual behavior education and actively carry out health education among young and middle-aged people.

Value of the nomogram based on HALP score in predicting the prognosis of patients with hepatocellular carcinoma after hepatectomy / 临床肝胆病杂志

Objective To investigate the value of HALP score in evaluating the prognosis of patients with hepatocellular carcinoma (HCC) after hepatectomy and whether the nomogram based on HALP score could effectively predict the postoperative survival of patients. Methods A retrospective study was performed for the clinical data of 253 HCC patients who underwent surgical treatment in Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, from July 2013 to March 2020. The receiver operating characteristic (ROC) curve was plotted to calculate the optimal cut-off values of HALP score and other related indicators; the chi-square test was used to investigate the association between HALP score and clinicopathological features; the Kaplan-Meier method was used to plot survival curves, and the Log-rank test method was used for comparison. The univariate and multivariate Cox regression analyses were used to investigate the association of HALP score and other clinical parameters with the prognosis of patients. R3.6 was used to establish a nomogram; C-index and calibration curve were used to evaluate the predictive ability of the nomogram, and net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to compare predictive ability between the nomogram model and the conventional model. Results The Kaplan-Meier analysis showed that the high HALP group had significantly better overall survival (OS) and recurrence-free survival (RFS) than the low HALP group ( P < 0.001). The univariate Cox regression analysis showed that white blood cell count, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), alpha-fetoprotein (AFP), surgical approach, microvascular invasion, TNM stage, degree of tumor differentiation, HALP, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR) were significantly associated with OS (all P < 0.05). The variables with statistical significance in the univariate Cox regression analysis were included in the multivariate Cox regression analysis, and the results showed that ALP, AST/ALT ratio, ALP, AFP, degree of tumor differentiation, and TNM stage were independent influencing factors for OS after surgery in HCC patients (all P < 0.05). The univariate Cox regression analysis showed that GGT, ALP, AFP, microvascular invasion, TNM stage, degree of tumor differentiation, HALP, AST/ALT ratio, NLR, and MLR were significantly associated with RFS (all P < 0.05), and the multivariate Cox regression analysis showed that HALP, AST/ALT ratio, NLR, ALP, AFP, and TNM stage were independent influencing factors for RFS after surgery in HCC patients (all P < 0.05). The nomograms for OS and RFS of HCC patients were established based on the multivariate analysis. The nomogram for OS had a C-index of 0.732 (95% confidence interval [ CI ]: 0.691-0.774) and an area under the ROC curve of 0.795, 0.791, and 0.775, respectively, in predicting 1-, 3-, and 5-year survival rates, and the nomogram for RFS had a C-index of 0.677 (95% CI : 0.637-0.717) and an area under the ROC curve of 0.742, 0.733, and 0.716, respectively, in predicting 1-, 3-, and 5-year survival rates. The calibration curves of 1-, 3-, and 5-year OS were well fitted to those of 1-, 3-, and 5-year RFS. Conclusion A low level of HALP before surgery is a predictive factor for poor long-term prognosis in HCC patients undergoing surgical treatment, and the nomogram model based on HALP score is superior to the BCLC staging model and can better predict the prognosis of HCC.

Chiral separation methods and the applications in the study of chiral components of traditional Chinese medicines / 药学学报

Chirality is one of the fundamental properties of nature, and most of the important molecules in living organisms contain chiral structures. The efficacy and safety of drugs are often closely related to the chiral structure of compounds, however, there are relatively more studies on synthetic characterization, pharmacology, and toxicology of chiral small molecule chemical drugs, but relatively less studies on chiral compounds contained in natural drugs such as traditional Chinese medicines. Chiral separation, as the basis of chiral research, has a pivotal position in the study of chiral compounds. In this paper, we systematically describe the separation methods of chiral compounds from the classification of chiral splitting methods based on chromatographic and non-chromatographic methods, as well as chromatographic packing materials, chiral additives and chiral derivatization, and review the chiral compounds in natural drugs such as traditional Chinese medicines reported in the past ten years, in order to provide references for the splitting and evaluating the activity of chiral compounds, and the improvement of quality standards of traditional Chinese medicines.

Application of single-pass four-throw releasable suture drainage tube ligation technique in Ahmed glaucoma valve implantation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the application of single-pass four-throw releasable suture drainage tube ligation technique in Ahmed glaucoma valve(AGV)implantation.METHODS: A total of 78 patients(78 eyes)with refractory glaucoma who underwent AGV implantation in the People's Hospital of Leshan from May 2020 to January 2022 were retrospectively analyzed. According to the treatment, the patients were divided into the modified AGV implantation group, with 43 patients(43 eyes)treated by modified AGV implantation, ligating the drainage tube with single-pass four-throw releasable suture, and the traditional AGV implantation group, with 35 patients(35 eyes)treated by traditional AGV implantation. Followed-up for 6mo, the intraocular pressure(IOP), success rate and complications were observed at 1d, 1 and 2wk and 1 and 6mo after operation.RESULTS: Postoperative IOP at all follow-up visits was significantly lower than that before surgery in both groups(all P&#x003C;0.05). There was no significant difference in IOP between groups at all follow-up visits(all P&#x003E;0.05). The incidence of shallow anterior chamber was 5% in the modified AGV implantation group and 23% in the traditional AGV implantation group at 1wk after surgery(P&#x003C;0.05). At 6mo after operation, the overall success rate was 98% in modified AGV implantation group and 89% in the traditional AGV implantation group(P&#x003E;0.05).CONCLUSION:During AGV implantation, ligation of drainage tube with single-pass four-throw releasable suture can effectively reduce IOP and reduce the incidence of shallow anterior chamber in early postoperative stage. Furthermore, the technique is safe and efficacious.

Advances in diagnosis,prevention and treatment of flexible flatfoot in children / 中国学校卫生

Abstract@#Flexibleis an important classification of flat foot. Flatfoot occurs due to a variety of reasons and causes the medial longitudinal arch to collapse or disappear. However, many children still do not develop a normal foot arch as the grow, and a failure to intervene in a timely manner will greatly harm a child s normal mobility development. Timely detection and intervention are the key to improve the prognosis. There is a lack of uniform quantitative criteria for the diagnosis of flexible flatfoot. Currently, the commonly used diagnostic methods include physical examination, foot printing, plantar pressure test and imaging examination. This article reviews the risk factors, diagnosis, prevention and treatment of Flexible Flatfoot.

Applicability comparison between Chinese dry eye questionnaire and ocular surface disease index questionnaire among college students / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the applicability of Chinese dry eye questionnaire in college students using the ocular surface disease index(OSDI)questionnaire as a reference.METHODS: Cross-sectional study. A total of 711 college students from Nanyang Medical College were enrolled in the study and assessed for dry eye condition using OSDI questionnaire and Chinese dry eye questionnaire. The response rate of each question in the two questionnaires was counted. Cronbach α was calculated to evaluate the internal consistency of both questionnaires. Correlation between the total scores of the two questionnaires was analyzed to evaluate the criterion validity. Based on OSDI scores, the discriminant validity of Chinese dry eye questionnaire was evaluated; receiver operating characteristic(ROC)curves was plotted for Chinese dry eye questionnaire scores, area under the ROC curve(AUC)was calculated, and diagnostic thresholds and corresponding sensitivity and specificity were also analyzed.RESULT: The response rates of the 12 questions on the OSDI questionnaire were 33.2%-100.0%, while it was 100.0% for each question on the Chinese dry eye questionnaire. The Cronbach α values of OSDI questionnaire and Chinese dry eye questionnaire were 0.905 and 0.789, respectively. The Chinese dry eye questionnaire score was positively correlated with the OSDI score(rs=0.712, P&#x003C;0.001). According to OSDI questionnaire scores, dry eye severity was divided into normal group, mild dry eye group, moderate dry eye group and severe dry eye group. The scores of Chinese dry eye questionnaire in these groups were 4.00(2.00, 6.00), 9.00(7.00, 11.00), 12.00(9.00, 14.00)and 16.00(13.50, 22.00), respectively, which increased with the severity of dry eye, and the overall difference was statistically significant(P&#x003C;0.001), as well as pairwise comparison between groups(P&#x003C;0.05). The AUCs of Chinese dry eye questionnaire in distinguishing normal population from dry eye population, mild dry eye from moderate dry eye, moderate dry eye from severe dry eye were 0.862, 0.661 and 0.769, respectively, and the diagnostic thresholds were 6.5, 11.5 and 14.5, respectively.CONCLUSION:Chinese dry eye questionnaire has an equivalent reliability, validity, discriminant ability and better response rate for dry eye screening and epidemiological survey among college students in China compared with OSDI questionnaire.

Effect and Mechanism of Nongsuo Dangguiwan in Relieving Oxidative Stress in Premature Ovarian Insufficiency Rats Based on Nrf2/HO-1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Nongsuo Dangguiwan in improving ovarian oxidative stress in rats with ovarian dysfunction. MethodThirty-six adult female SD rats were randomly divided into normal group， model group， positive drug group （Femoston， 0.3 mg·kg-1）， and high-， medium-， and low-dose groups of concentrated Nongsuo Dangguiwan （2.08， 4.16， 8.32 g·kg-1）， with six rats in each group. Rats， except for those in the normal group， were injected with 80 mg·kg-1 vinyl cyclohexene dioxide （VCD） per day for 14 consecutive days to induce ovarian dysfunction. From the 15th day， rats were treated with corresponding drugs by gavage， while those in the model group received 2 mL·kg-1 saline， once daily for 28 consecutive days. The ovarian index， levels of related hormones including estradiol （E2）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and anti-mullerian hormone （AMH） in serum， as well as superoxide dismutase （SOD） activity and glutathione （GSH） content in serum were measured by enzyme-linked immunosorbent assay （ELISA）. The malondialdehyde （MDA） content in serum was detected by the thiobarbituric acid （TAB） method. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. The expression of nuclear factor E2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， SOD2， and SOD1 in ovarian tissues was detected by immunohistochemistry （IHC） and Western blot. ResultCompared with the normal group， the model group showed a significant reduction in growing follicles in the ovary， loose arrangement of granulosa cells in the follicle， decreased body weight， ovarian index， and serum AMH and E2 levels， increased LH and FSH levels （P<0.01）， reduced levels of SOD and GSH in serum （P<0.01）， and increased MDA level （P<0.01）. Compared with the model group， the groups with drug intervention showed increased ovarian index （P<0.05， P<0.01）， increased serum E2 level （P<0.05， P<0.01）， decreased FSH， AMH， and LH levels （P<0.05， P<0.01）， increased number of growing follicles in the ovary， potentiated SOD activity in serum， increased GSH content， decreased MDA content （P<0.05， P<0.01）， and up-regulated expression levels of Nrf2， HO-1， SOD2， and SOD1 proteins in ovarian tissues （P<0.05， P<0.01）. ConclusionNongsuo Dangguiwan can regulate serum hormone levels， increase the expression of Nrf2， HO-1， SOD2， and SOD1 in ovarian tissues， and improve ovarian antioxidant capacity to resist oxidative stress injury， thereby improving ovarian reserve function.

Advances in the application of nonselective β-receptor blockers in treatment of liver cirrhosis / 临床肝胆病杂志

Nonselective β-receptor blockers (NSBBs) are first-line drugs for the prevention and treatment of complications in cirrhotic patients with portal hypertension and are widely used in the primary and secondary prevention of esophagogastric variceal bleeding. In recent years, studies have shown that in patients with clinically significant portal hypertension (CSPH), NSBBs can used to prevent liver decompensation events besides variceal bleeding, such as ascites and hepatic encephalopathy. However, in patients without CSPH, current research evidence does not support the use of NSBBs. Although reliable data currently support the use of NSBBs in end-stage liver cirrhosis, there are still drug safety issues in patients with refractory ascites and spontaneous bacterial peritonitis, and further studies are needed to explore the dose and timing of administration. This article reviews the clinical research advances in the use of NSBBs (especially carvedilol) in patients with liver cirrhosis and summarizes the therapeutic window used reasonably in the whole-course management of liver cirrhosis, so as to provide a basis for clinical decision-making.

Trihalomethanes and haloacetamides as disinfection by-products in different types of drinking water of Wuxi / 环境与职业医学

Background The concentrations of disinfection by-products (DBPs) are varied by different water sources, disinfectants, or treatment processes in Wuxi, and the associated health risks are also different. Objective To understand the levels of trihalomethanes (THMs) and haloacetamides (HAcAms) in drinking water in Wuxi, and their variations by water sources, seasons, disinfectants or treatment processes, aiming to provide technical support for ensuring the safety of drinking water. Methods In dry period (December 2019) and wet period (July 2020), the finished water and tap water (from the beginning, middle, and end of the drinking water distribution network) from 12 centralized water treatment plants in Wuxi were collected to detect the concentrations of THMs and HAcAms in water samples. A purge and trap-gas chromatography-mass spectrometry method was applied to detect trichloromethane (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and tribromomethane (TBM), and a solid-phase extraction-gas chromatography-mass spectrometry method to detect dichloroacetamide (DCAcAm), trichloroacetamide (TCAcAm), bromochloroacetamide (BCAcAm), dibromoacetamide (DBAcAm), bromodichloroacetamide (BDCAcAm), dibromochloroacetamide (DBCAcAm), and tribromoacetamide (TBAcAm). Analyses and comparisons were made on the concentrations of THMs and HAcAms in drinking water by water sources (the Yangtze River/the Taihu Lake/reservoir), wet/dry seasons, disinfection methods (liquid chlorine/sodium hypochlorite), and treatment processes (conventional treatment/conventional+advanced treatment). Results A total of 96 drinking water samples were collected in Wuxi. THMs were positive in all the water samples (100%), with concentration ranging from 1.027 to 40.225 μg·L−1 and the M (P25, P75) concentration being 24.782 (17.784, 30.932) μg·L−1. None of the 4 THMs exceeded the standard limit of the Standards for drinking water quality (GB 5749-2022 ), and the order of the 4 THMs concentrations from high to low was TCM > BDCM > DBCM > TBM. Five of the 7 HAcAms were detected, the total concentration ranged from 0.137 to 3.288 μg·L−1, and the M (P25, P75) was 0.808 (0.482, 1.704) μg·L−1. The DCAcAm concentration was the highest (2.448 μg·L−1), followed by BCAcAm, while TCAcAm and DBCAcAm were not detected. The M (P25, P75) of the total concentration of THMs in the drinking water from the Taihu Lake was 33.353 (26.649, 36.217) μg·L−1, that of the Yangtze River was 27.448 (24.312, 31.393) μg·L−1, and both were higher than the level of the reservoir [16.359 (2.305, 21.553) μg·L−1] (P<0.05), while the M (P25, P75) of the total concentration of HAcAms in the drinking water from the Taihu Lake was 0.616 (0.363, 0.718) μg·L−1, which was lower than those of the Yangtze River [0.967 (0.355, 2.283) μg·L−1] and the reservoir [1.071 (0.686, 1.828) μg·L−1] (P<0.05). There were no statistically significant differences in the total concentrations of THMs and HAcAms between wet season and dry season, or between different disinfection methods (P>0.05). The M (P25, P75) concentrations of THMs and HAcAms in drinking water after advanced treatment process involving ozone, activated carbon, and membrane were 20.565 (3.316, 27.185) μg·L−1 and 0.623 (0.452, 1.286) μg·L−1 respectively, and were lower than the corresponding values after conventional treatment process, 28.740 (23.431, 35.085) μg·L−1 and 0.934 (0.490, 2.116) μg·L−1 respectively (P＜0.05). Conclusion The concentrations of THMs and HAcAms in drinking water in Wuxi are generally at a low level. The levels of controlled THMs meet the requirements of national standards, and the levels of uncontrolled HAcAms as new DBPs are up to μg·L−1. The concentrations of the two kinds of DBPs in drinking water vary by water sources. The concentrations of THMs and HAcAms produced by the advanced treatment process are lower than that by the conventional treatment process.

Actively separated microneedle patch for sustained-release of growth hormone to treat growth hormone deficiency

Growth hormone deficiency (GHD) has become a serious healthcare burden, and presents a huge impact on the physical and mental health of patients. Here, we developed an actively separated microneedle patch (PAA/NaHCO3-Silk MN) based on silk protein for sustained release of recombinant human growth hormone (rhGH). Silk protein, as a friendly carrier material for proteins, could be constructed in mild full-water conditions and ensure the activity of rhGH. After manually pressing PAA/NaHCO3-Silk MN patch to skin for 1 min, active separation is achieved by absorbing the interstitial fluid (ISF) to trigger HCO3 ‒ in the active backing layer to produce carbon dioxide gas (CO2). In rats, the MN patch could maintain the sustained release of rhGH for more than 7 days, and produce similar effects as daily subcutaneous (S.C.) injections of rhGH in promoting height and weight with well tolerated. Moreover, the PAA/NaHCO3-Silk MN patch with the potential of painless self-administration, does not require cold chain transportation and storage possess great economic benefits. Overall, the PAA/NaHCO3-Silk MN patch can significantly improve patient compliance and increase the availability of drugs, meet current unmet clinical needs, improve clinical treatment effects of GHD patients.

Intermittent heat exposure induces thoracic aorta injury in spontaneously hypertensive rats by activating the AMPK/mTOR/ULK1 pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of different manners of heat exposure on thoracic aorta injury in spontaneously hypertensive rats (SHRs) and explore the underlying mechanism.@*METHODS@#Normal 6 to 7-week-old male SHRs were randomized into control group (cage at room temperature), intermittent heat exposure group (SHR-8 group, exposed to 32 ℃ for 8 h daily for 7 days) and SHR-24 group (with continuous exposure to 32 ℃ for 7 days). After the treatments, the pathologies of the thoracic aorta of the rats were observed with HE staining, and the expressions of Beclin1, LC3B and p62 were detected with Western blotting and immunofluorescence assay; TUNEL staining was used to observe cell apoptosis in the thoracic aorta, and the expressions of caspase-3, Bax, and Bcl-2 were detected using Western blotting. The effects of intraperitoneal injections of 3-MA (an autophagy agonist), rapamycin (an autophagy inhibitor) or compound C 30 min before intermittent heat exposure on the expressions of proteins associated with autophagy, apoptosis and the AMPK/mTOR/ULK1 pathway in the aorta were examined with immunohistochemistry.@*RESULTS@#In SHR-8 group, the rats showed incomplete aortic intima with disordered cell distribution and significantly increased expressions of Beclin1, LC3II/LC3I and Bax, lowered expressions of p62 and Bcl-2, and increased apoptotic cells in the thoracic aorta (P < 0.05). Pretreatment with 3-MA obviously inhibited the expressions of autophagy- and apoptosis-related proteins, whereas rapamycin promoted their expressions. Compared with the control group, the rats in SHR-8 group had significantly down-regulated p-mTOR and up-regulated p-AMPK and p-ULK1 expression of in the aorta; Treatment with compound C obviously lowered the expressions of p-AMPK and p-ULK1 and those of LC3B and Beclin1 as well.@*CONCLUSION@#In SHRs, intermittent heat exposure causes significant pathologies and promotes autophagy and apoptosis in the thoracic aorta possibly by activating the AMPK/mTOR/ULK1 pathway.

Construction of pharmacogenomics-guided individualized medication list for elderly patients / 中国药房

OBJECTIVE To develop an individualized medication list for elderly patients by evidence-based pharmacy method， and to support clinical decisions on rational use of METHODS　Firstly， drugs with risk genetic information were screened out by systematically reviewing evidence-based pharmacy information. Secondly， researchers investigated the included drugs in lists from different data E- sources. Drugs included in three or more data sources and drugs proposed by the expert committee were then included in the medication list. Thirdly， for the drugs included in two data sources， researchers designed questionnaires to investigate the necessity of drug-related gene testing. According to the scoring results of the expert questionnaire， drugs with higher scores were included in the list. Data sources included real-world data （list of high frequency medication in hospitals， high frequency medication for elderly outpatients and inpatients in National Health Care Claims Data， drugs related to frequent medication errors and so on） and evidence-based pharmacy evidence （the websites of Clinical Pharmacogenomics Implementation Consortium， Dutch Pharmacogenetics Working Group， Food and Drug Administration and so on）. RESULTS　The study obtain 68 drugs with risk genetic information which were included in three data sources. Combined with 23 drugs proposed by the expert committee， a list containing 74 drugs was preliminarily formed after de-duplication. A total of 37 drugs included in two databases with risk genetic information were scored through the questionnaire survey to form a supplementary list of 26 drugs. This is the final composition of the list of 100 drugs developed in this study. Among them， there are 43 drugs for the central nervous system， 15 drugs for the cardiovascular system， 12 anti-tumor drugs and so on. Twelve drugs were included in six or more data sources， which mainly consisted of drugs for digestive system， all proton pump inhibitors. CONCLUSION　In this study， a list of 100 commonly used drugs which require individualized medication for the elderly was developed by evidence-based pharmacy method. The drug list will be updated in time as available evidence changes， and can provide guidance for rational use of medicines for elderly patients.

Investigation on blood lead level of workers in a lead-acid battery factory in Wuhan / 公共卫生与预防医学

Objective To investigate the occupational lead exposure and blood lead levels of workers in a lead-acid battery factory in Wuhan in 2020 and analyze the influencing factors of blood lead, and to provide reference for the blood lead intervention of the workers in the lead-acid battery factory. Methods The blood lead test results of 320 occupational lead-exposed workers in the factory were investigated and the influencing factors were analyzed. Results Among the 320 blood lead samples collected, 4 people had blood lead≥400 μg/L, accounting for 1.25%, and 89 people had blood lead≥200 μg/L, accounting for 27.81%. Among them, there were 235 males with a median blood lead of 155.10 μg/L, and 85 females with a median blood lead of 82.40 μg/L. The Wilcoxon rank sum test results of two independent samples showed that the overall blood lead level of male employees was higher than that of female employees, and the difference was statistically significant (P 50 years old. Using the Bonferroni method to adjust the significance level for pairwise comparison, it was found that there were significant differences in the blood lead concentrations between the group under 40 years old, the group of 40 - 50 years old, and the group of over 50 years old ( P < 0.016 after adjustment). The employees were classified into different workshops, including 38 samples from the administrative workshop , 40 samples from the charging workshop, and 242 samples from the assembly workshop. Using the Bonferroni method to adjust the significance level for pairwise comparison, it was found that the blood lead concentrations in the administrative workshop, the charging workshop, and the assembly workshop were statistically different ( P <0.016 after adjustment). Conclusion The age, gender, and type of work of the employees in the battery factory all have a certain impact on the blood lead level. It is necessary to continuously improve the management of the labor hygiene operation system and strengthen the self-protection level of the workers, and regularly carry out occupational hygiene inspection and health monitoring.

Progress in the role of peritubular capillary injury in kidney transplantation / 器官移植

Kidney is a highly vascularized organ and peritubular capillary network constitutes the critical component of its microvascular system. Peritubular capillaries, as the main vessels for blood supply in renal tubules and renal interstitium, involve in important physiological processes in renal tubules such as energy metabolism, substance secretion and reabsorption. In recent years, it has been demonstrated that ischemia-reperfusion injury, rejection and renal fibrosis during kidney transplantation would result in compromised structural integrity and decreased number in peritubular capillaries, thus leading to interstitial fibrosis in renal allograft, which would seriously affect the long-term stability of renal function in the renal allograft. Therefore, we reviewed the structure and function of peritubular capillary, peritubular capillary and ischemia-reperfusion injury, rejection and renal allograft fibrosis, focusing on the mechanism for peritubular capillary injury in kidney transplantation and the specific changes manifested, with the aim of providing a reference for preventing and treating perioperative complications in kidney transplantation and improving the long-term prognosis of grafts.

Accuracy of different intraocular lens power calculation formulas in cataract patients with shallow anterior chamber: a meta-analysis / 中华实验眼科杂志

Objective:To systematically compare the accuracy of intraocular lens (IOL) power calculation formulas in cataract patients with shallow anterior chamber.Methods:A comprehensive literature search was conducted in MEDLINE, EMBASE, Cochrane Library, and the Chinese databases including CNKI, Wanfang, and VIP databases.The peer-reviewed literature on the accuracy of IOL power calculation formulas in cataract patients with shallow anterior chamber was searched from the establishment of the database until August 2020.Literature screening, data extraction and quality assessment were performed according to inclusion and exclusion criteria.The mean difference ( MD) of mean absolute error (MAE) among different formulas was analyzed.Meta-analysis was performed using Revman 5.3 software. Results:Seven studies involving 499 eyes were included.The accuracy of six formulas, Barrett Universal Ⅱ, Haigis, SRK/T, Hoffer Q, Holladay 1 and Holladay 2, was evaluated.The MAE of Barrett Universal Ⅱ was significantly lower than that of Hoffer Q ( MD=0.11 D; 95% CI: 0.05-0.17 D; P<0.001), Haigis ( MD=0.08 D; 95% CI: 0.03-0.13 D; P=0.002), and Holladay 2 ( MD=-0.06 D; 95% CI: -0.11--0.01 D; P=0.020). No significant difference was found in the remaining pairwise comparisons (all at P>0.05). Conclusions:The Barrett Universal Ⅱ formula is more accurate than Hoffer Q, Haigis, and Holladay 2 formulas in predicting IOL power in cataract patients with shallow anterior chamber.