The influence of application-audit system for doctoral enrollment on scientific research ability and employment development of medical graduate students / 中华医学教育探索杂志

Objective:To investigate and analyze the differences of PhD student scientific research ability, employment and development among types of postgraduate students that admitted by various of doctoral admissions under the perspective of medical students to assess and optimize the existing applications-audit system (AAS).Methods:A self-compiled questionnaire was used to investigate the opinions of medical students at different grades and types on the AAS related issues. Excel and SPSS were used to perform frequency statistics, chi-square test and independent sample t-test. Results:The PhD enrolled from AAS tended to complete the paper-publication at first and second year (38.71%, 12/31; 35.48%, 11/31), while unified enrollment (UE) tended to complete in the second year (33.33%, 10/30) and seven-year degree (SYD) in the third year (40.54%, 15/37) ( P=0.021). In terms of the value of the materials required in the application stage to the doctoral research, 74.19%(23/31) of AAS students and 48.65%(18/37) of SYD students believed that scientific research results were the most helpful to the doctoral research process, while UE believed that English helped the most (26.67%, 8/30), with significant differences among groups ( P=0.002). In terms of fair recognition of enrollment in the application system, 71.53% (304/425) of graduate students believed that AAS for doctoral enrollment was fair. The institution ( P=0.001) and type of master's degree ( P=0.001) significantly affected graduate students' recognition of the fairness of AAS. Conclusion:The degree and speed of dissertation completion of the AAS PhD are prior, reflecting the advantages of AAS in the cultivation of medical doctors' scientific academic ability and achievements. The AAS plays a significant role in enhancing the reserve of high-level scientific researchers in China, and has a high recognition and influence in medical students. In the future, the application examination system will be optimized to create the most suitable way for doctoral enrollment in China.

The effect of "ten needles in the stomach" treatment on sleep perception for the patients with spleen-gastric damp-heat insomnia based on the theory of "stomach upset, sleep restlessness" / 国际中医中药杂志

Objective:To explore the effect of "ten needles in the stomach" on sleep perception of patients with spleen-gastric damp-heat insomnia based on the theory of "stomach discord, then sleep restlessness", to provide references for clinical diagnosis and treatment.Methods:The study subjects were 300 patients with insomnia from the sleep department and outpatient department of Shijiazhuang Traditional Chinese Medicine Hospital. According to the random number method, they were divided into the stomach ten needle group, the diazepam group, and the stomach ten needle plus diazepam group, with 100 in each group. Among them, the stomach ten needles group received "stomach ten needles" acupuncture treatment, the diazepam group was given diazepam therapy, and the stomach ten needles plus diazepam group was given diazepam combined with "stomach ten needles" acupuncture treatment. The Pittsburgh Sleep Quality Index (PSQI) scores, the self-rating disease symptom scale (SCL-90) scores, nighttime polysomnography (PSG) monitoring indicators, and the mean sleep latency (MSL) values were compared before and after treatment in the three groups. The difference in clinical efficacy between the two groups were observed.Results:The total effective rate was 94.0% (94/100) in the combined group, 77.0% (77/100) in the diazepam group, and 85.0% (85/100) in the stomach ten needle group. There were significant differences among the three groups ( χ2=11.56, P<0.01). After treatment, the daytime dysfunction, hypnotic drugs, sleep disturbance, sleep efficiency, sleep time, sleep time, sleep quality score and total score of the combined group were significantly lower than those in the diazepam group and the stomach ten needle group ( F=5.70, 3.65, 5.23, 6.37, 3.66, 6.19, 7.54, 6.40, all Ps<0.01); The scores of SCL-90 and MSL were significantly lower than those in the diazepam group and stomach ten needle group ( F=8.97, 7.53, all Ps<0.01). In the combined group, NWAK [(1.36 ± 0.87) times vs. (2.69 ± 1.15) times, (2.11 ± 1.05) times, F=5.88], SOL [(13.62 ± 5.85) min vs. (25.06 ± 9.42) min, (19.78 ± 7.63) min, F=6.49], N1/TST [(5.69 ± 1.09)% vs. (12.65 ± 2.58)%, (8.49 ± 2.45)%, F=5.13], N2/TST [(51.07 ± 10 2.06)% vs. (58.36 ± 2.18)%, (55.61 ± 2.04)%, F=9.86] were significantly lower than those in the diazepam group and stomach ten needle group ( P<0.01), SE [(90.33 ± 2.89)% vs. (85.39 ± 2.75)%, (87.53 ± 2.69)%, F=8.36], TST [(449.32 ± 23.65) min vs. (421.66 ± 25.33) min, (431.26 ± 25.98) min, F=8.26], REM/TST [(23.87 ± 4.52)% vs. (14.52 ± 3.87)%, (18.36 ± 3.25)%, F=5.34], N3/TST [(18.69 ± 2.02)% vs. (10.31 ± 1.64)%, (14.89 ± 1.74)%, F=7.69] were significantly higher than those in the diazepam group and stomach ten needle group ( P<0.01). Conclusion:Based on the "stomach discord, sleep restlessness" theory, the ten needles on the stomach can treat insomnia and improve psychological state and sleep quality, with the functions of clearing the damp and heat of the middle joker, regulating the lifting and lowering of qi in the middle.

Effects of shift work on adipokines, inflammatory factors, and insulin sensitivity in non-overweight/obese women / 中华内分泌代谢杂志

Objective:To observe the effect of shift work on the stability of the circadian clock and insulin sensitivity in non-overweight/obese individuals with normal blood glucose, and explore underlying connection.Methods:Female shift working nurses in the Department of Blood Transplantation and non-shift working nurses in the Health Management Center in the First Affiliated Hospital of Zhengzhou University were divided into shift worker group (SW group) and non-shift worker group (NSW group). Serum inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α)], adipokines (adiponectin, leptin, chemerin, visfatin), and melatonin levels were measured using enzyme linked immunosorbent assay (ELISA). Realtime fluorescence quantitative PCR was performed to detect peripheral blood circadian clock genes circadian locomotor output cycles protein kaput(Clock) and brain and muscle ARNT-like protein 1(Bmal1). Cortisol and fasting insulin were measured by chemiluminescent microparticle immunoassay, and HbA 1C was measured by capillary electrophoresis. In addition, visceral fat area (VFA) was assessed with bioelectrical impedance analyzer, and mid-sleep time composite phase deviations (CPD) was calculated based on the International Physical Activity Short Questionnaire. Results:SW group had lower serum level of melatonin ( P=0.023) and higher cortisol ( P=0.001) than the NSW group, and altered mRNA expression of Clock and Bmal1 ( P=0.034, P=0.047). Fasting blood glucose and HbA 1C in the SW group, although in the normal range, had been higher than in the NSW group ( P=0.011, P=0.033). Although body mass index was normal in SW group, VFA had been higher than that of the NSW group ( P=0.010). And homeostasis model assessment for insulin resistance (HOMA-IR), IL-6, TNF-α, leptin, chemerin, and visfatin were significantly higher in the SW group than NSW group ( P=0.033, P=0.012, P=0.001, P=0.011, P=0.021, P=0.007). In addition, adjusting for body mass index and activity factors revealed a significant positive correlation between CPD and VFA ( r=0.434, P=0.049), inflammatory factors IL-6 ( r=0.514, P=0.017) and TNF-α ( r=0.700, P<0.001) and pro-inflammatory adipokines leptin ( r=0.473, P=0.030), chemerin ( r=0.439, P=0.047), visfatin ( r=0.521, P=0.015). Conclusion:Shift work can affect circadian clock, with increased visceral adiposity, pro-inflammatory adipokines, inflammatory factors and decreased insulin sensitivity in women without overweight/obese.

Gene Mutation and Overexpression of Newly Diagnosed Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients.@*METHODS@#Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH).@*RESULTS@#Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression.@*CONCLUSION@#There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.

Effect analysis of trajectory screw technique in fragility fracture of pelvic ring / 中国骨伤

OBJECTIVE@#To assess the clinical efficacy of minimally invasive technology with trajectory screw fixation for fragility fractures of pelvic(FFP).@*METHODS@#A retrospective case control study was performed to analyze the clinical data of 35 patients with FFP who were treated and followed up between January 2016 and December 2019. There were 12 males and 23 females, aged from 65 to 99 years with an average of(75.4±7.8) years old. There were 13 cases of type Ⅱb, 7 cases of type Ⅱc, 8 cases of type Ⅲa, 2 cases of type Ⅲb, 2 cases of type Ⅲc, 1 case of type Ⅳb, and 2 cases of type Ⅳc according to Rommens FFP comprehensive classification. All patients received the treatment of minimally invasive technology with trajectory screws fixation. According to the different methods of anterior pelvic ring fixation, FFP patients were divided into two groups:12 cases were fixed with the pedicle screw rod system in the anterior pelvic subcutaneous internal fixator (INFIX) group;23 cases were fixed with hollow screws of the pubic symphysis, superior ramus of pubis or acetabular anterior column in the screw group. The operation time, intraoperative blood loss, intraoperative fluoroscopy times, length of hospital stay, cost of internal fixation, pre- and post-operative visual analogue scale(VAS) were compared between the two groups. The fracture reduction quality was evaluated according to the Matta criteria, and the clinical function was evaluated by the Majeed functional scoring system respectively.@*RESULTS@#All patients were followed up for 12 to 39(16.5±5.4) months after surgery. There was no statistically significant difference in the operation time, intraoperative blood loss, intraoperative fluoroscopy time, and length of hospital stay between the two groups(P>0.05). As for the cost of internal fixation, the cost of internal fixation in the screw group [2 914 (2 914, 4 371) yuan] was significantly lower than that of the INFIX group [6 205 (6 205, 6 205) yuan] (P<0.05). No significant difference was observed in the incidence of postoperative complications between the two groups (P>0.05). There was no significant difference in VAS assessment at admission, 1 week, and 3 months after surgery between the two groups(P>0.05). However, the VAS assessment at 1 week and 3 months after surgery of the two groups were significantly better than those at admission(P<0.05). There was no significant difference in the quality of fracture reduction after the operation and the efficacy evaluation at the last follow-up between the two groups(P>0.05).@*CONCLUSION@#For the treatment of fragility fractures, minimally invasive technology with trajectory screw fixation can achieve good clinical efficacy. It has the advantages of being relatively minimally invasive, less bleeding, relieving the pain. It deserves clinical application.

Effect of Toxoplasma gondii Chinese 1 genotype infections on brain iron metabolism in mice / 中国血吸虫病防治杂志

Objective To investigate the effect of Toxoplasma gondii Chinese 1 genotype infections on host brain iron metabolism and brain damages. Methods Twenty C57BL/6 mice, each weighing 15 to 17 g, were randomly divided into the control and infection groups, of 10 mice in each group. Each mouse in the infection group was injected intraperitoneally with 4 000 tachyzoites of the TgCtwh3 isolate with Chinese 1 genotype, while each mouse in the control group was injected with an equal amount of sterile phosphate-buffered saline (PBS). All mice were sacrificed 6 day post-infection and brain tissues were sampled. The iron levels were measured in mouse brain specimens using inductively coupled plasma mass spectrometry (ICP-MS). The differentially expressed genes were determined between the experimental and control groups using RNA chips and Gene Ontology (GO) term enrichment analysis of differentially expressed genes was performed. The mRNA expression of Toxoplasma gondii surface antigen 1 (TgSAG1) gene and some Zrt- and Irt-like protein (ZIP) family member coding genes was detected by quantitative real-time PCR (qPCR) assay. The ultrastructure of the hippocampus dentate gyrus in mouse brain specimens was observed using optical and electronic microscopy. The glutathione peroxidase 4 (GPx4) expression was determined using Western blotting, and malondialdehyde (MDA) level was measured using thiobarbituric acid (TBA) test. In addition, the optical density (OD) of vascular endothelial growth factor (VEGF) protein was measured using immunohistochemistry. Results Optical microscopy showed cell necrosis in the hippocampus dentate gyrus of mouse brain specimens in the infection group, and electronic microscopy cytoplasmic vacuolization, nuclear atrophy and necrosis, disruption of cristae mitochondriales and increased autophagosome levels in the mouse brain hippocampus specimens in the infection group. The iron level was significantly greater in mouse brain specimens in the infection group than in the control group [(32.92 ± 0.90) μg/g vs. (37.72 ± 1.10) μg/g; t = 3.397, P < 0.01]. RNA chips revealed 721 up-regulated genes and 276 down-regulated genes in mouse brain specimens between the infection and control groups, and the differentially expressed genes were significantly enriched in metal ion binding ability (molecular function). Elevated expression of metal element transporter ZIP2 mRNA (t = 8.659, P < 0.05), reduced GPx4 expression [(1.046 ± 0.025) vs. (0.720 ± 0.101); t = 3.129, P < 0.01], increased MDA level [(4.37 ± 0.33) nmol/mgprot vs. (5.93 ± 0.54) nmol/mgprot; t = 2.451, P < 0.05], and up-regulated mean OD of VEGF protein [(0.348 3 ± 0.017 8) vs. (0.490 6 ± 0.010 5); t = 6.641, P < 0.01] were found in mouse brain specimens in the infection group than in the control group. Conclusions Chinese 1 genotype T. gondii infection results in iron accumulation in brain tissues, reduced antioxidant ability and elevated levels of oxidative stress in mice, suggesting that T. gondii infection may cause brain damages through affecting iron metabolism in host brain tissues.

Oxidative Damage to BV2 Cells by Trichloroacetic Acid: Protective Role of Boron via the p53 Pathway / 生物医学与环境科学（英文）

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-β production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.

Laparoscopic surgery in colon cancer patients with end-stage renal disease / 中华普通外科杂志

Objective:To explore the efficacy and safety of laparoscopic colon cancer surgery for patients with end-stage renal disease .Methods:Thirty-one end-stage renal disease patients (continuous hemodialysis) underwent laparoscopic colon cancer surgery from Jan 2014 to May 2019 in Tianjin First Central Hospital compared to 35 colon cancer patients with normal renal function.Result:Compared with the control group, the operation time in laparoscopic group was longer[(187±20) min vs. (174±21) min, t=2.381, P=0.020], the intraoperative blood loss was more[90 (80-110) ml vs. 50(40-60) ml, Z=-6.580, P<0.001], the postoperative drainage volume was more[(417±89) ml vs.(208±67) ml, t=10.858, P<0.001], the postoperative hospitalization time was longer[(13.68±2.10) d vs.(9.09±1.65) d, t=9.918. P<0.001], and the total hospitalization costs were higher[9.2 (8.8-9.6) ten thousand yuan vs. 6.1 (5.8-6.5) ten thousand yuan, Z=-6.976, P<0.001]. There was no significant difference in overall morbidity between the two group (23% vs. 9%, P=0.170). Sixty-one patients (92%) were followed up for a median time of 6 months. One case of liver metastasis was found in each group. Conclusion:Laparoscopic colon cancer surgery can be a safe and effective procedure in patients with end-stage renal disease .

Analysis and Suggestions on National Drug Quality Disclosure System / 中国药房

OBJECTIVE：To provide reference for further improving the national drug quality disclosure system. METHODS ： The national drug quality disclosure system was analyzed in respects of general information ，implementation procedure ， implementation situation and effects ，and existing problems. The improvement suggestions were put forward. RESULTS & CONCLUSIONS：The national drug quality disclosure system had gone through the bulletin stage ，notice stage and announcement stage. At present ，it had become drug regulatory measure with timely release ，rigorous procedures and sanctions. The process of national drug quality disclosure included five steps ，ie. informing the sampling enterprises of the fact that the drugs were unqualified，controlling the risk of unqualified drugs ，providing legal relief to the notified units ，preparing the contents of the national drug quality notice ，and releasing the national drug quality notice to the public. In recent years ，National Medical Products Administration had made greater efforts to release the national drug quality notice. The release of the national drug quality notice has played an important role on forcing drug manufacturers to improve drug quality and enhance the credibility of drug regulatory departments. However ，there are also some problems ，such as the non-conforming report is not delivered in time ，the tracing time for suspected counterfeit TCM pieces is too long ，and the provincial drug regulatory bureau does not strictly control the first trial of complaints. It is suggested that National Medical Products Administration strengthen the training ，review and punishment of provincial drug regulatory departments ；at the same time ，provincial drug regulatory departments also need to strengthen responsibility and business capacity-building ，pay attention to relevant work and strengthen daily supervision.

Research Progress in Genetic Research of Fatigue / 中国实验方剂学杂志

Fatigue refers to the manifestation of disorders in the process of carrying out or maintaining random activities， which can be regarded as an independent disease or as a symptom in a variety of chronic diseases. The high incidence of fatigue has seriously affected people's physical and mental health， and the prevention and treatment of fatigue has become an important problem to be solved urgently. The pathogenesis of fatigue mainly includes energy consumpation， accumulation of metabolites， abnormal secretion of neurotransmitters， decline of mitochondrial function， dysfunction of hypothalamus pituitary adrenal axis， etc. At present， there is no unified understanding about the pathogenesis of fatigue at home and abroad. The gene research of fatigue is the current research frontier. Gene expression profiling provides a new method for the study of the mechanism of fatigue. The combination of gene chip technology and traditional Chinese medicine（TCM） theory is expected to bring a breakthrough in the study of the pathogenesis of fatigue. In the study of fatigue gene chip， messenger RNA（mRNA） and microRNA（miRNA） are the common research objects， but few explorations are focused on the gene expression rule of fatigue by a specific signaling pathway and the effective regulation targets of TCM for treating fatigue. In recent years， the dysfunction of reward and inhibition mechanism in the central nervous system has become a research hotspot. In particular， gamma amino butyric acid （GABA） and dopamine （DA） have attracted much attention as the main substances of inhibition and reward mechanism， respectively. GABA and DA are used as inhibition and reward mechanisms to maintain the balance， and the body will not feel fatigue. Once the balance is broken， the fatigue will be formed. At the same time， DA and GABA receptors can also regulate cyclic adenosine monophosphate signaling pathway（cAMP） to affect fatigue. The research on key genes in GABA/DA balance mechanism and related cAMP signaling pathway by gene chip technology is expected to reveal the pathogenesis of fatigue in depth. The gene chip method is used to detect the changes of key genes in GABA/DA pathway and the related cAMP signaling pathway in the fatigue population and the normal population， so as to further explore the pathogenesis of fatigue. In this paper， the key genes in GABA/DA balance mechanism and cAMP signaling pathway related to fatigue were summarized by using the review method， so as to provide the basis for further study on the pathogenesis of fatigue and effective prevention and treatment from the perspective of genetics.

Effect of Microelectronic Electromyography Bridge on Motor Function of Extensor Carpi Radialis Longus in Patients with Cervical Spinal Cord Injury / 中国康复理论与实践

Objective:To observe the effect of microelectronic EMG bridge (EMGB) training on the motor function of extensor carpi radialis longus in patients with complete cervical 5 spinal cord injury. Methods:From March, 2016 to March, 2017, 20 patients with complete cervical 5 spinal cord injury were randomly divided into control group (n = 10) and experimental group (n = 10). The control group received routine wrist extensor muscle training, and the experimental group received EMGB training in addition, for 180 days. The motor function of the affected limb was evaluated by sEMG of extensor carpi radialis longus, Manual Muscle Test (MMT), Wolf Motor Function Test (WMFT) and Spinal Cord Lesion Independence Measure (SCIM). Results:After treatment, the peak value and average value of sEMG of extensor carpi longus of both sides increased in both groups (t > 2.510, P < 0.05), the peak value and average value of the left side were higher (t > 2.759, P < 0.05), and the peak value of the right side was higher (t = 2.691, P < 0.05) in the experiment group than in the control group, however, there was no significant difference in average value of the right side between two groups (t = 2.063, P = 0.054). The scores of MMT increased in both groups (t > 2.569, P < 0.05), and were higher in the experimental group than in the control group (t > 2.278, P < 0.05). The scores of WMFT and SCIM increased in both groups (t > 3.839, P < 0.05), however, there was no significant difference between two groups (t < 1.498, P > 0.05). Conclusion:EMGB training could improve the motor function of extensor carpi radialis longus in patients with complete cervical 5 spinal cord injury.

Effect of CDK1 Interferes with the Regulation of PLK1, Aurora B and TRF1 on the Proliferation of Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of CDK1 interference regulation of PLK1, Aurora B and TRF1 on the proliferation of leukemia cells.@*METHODS@#The human myelogenous leukemia cell line HL-60 was selected as the research object, and the effect of TRF1 expression and its changes on cell proliferation and cycle was investigated by regulating intracellular CDK1 expression. The objects were divided into 5 groups, including control group, shRNA-NC group, CDK1-shRNA group, pcDNA group and pcDNA-CDK1 group. RT-PCR was used to detect the CDK1 expression of cells in each group; colony formation was used to detect the proliferation of the cells. Western blot was used to detect the expression of CDK1, PLK1, Aurora B, TRF1, and cyclin p53, p27, cyclinA.@*RESULTS@#The phosphorylation level of PLK1, Aurora B and the expression of TRF1 in the CDK1-shRNA group were significantly down-regulated as compared with those in the control group (P<0.05). Compared with the control group, the cells in CDK1-shRNA group showed lower clone formation rate, the increasing of cycle-associated proteins p53 and p27 and the decreasing of cyclinA expression (P<0.05). It was shown that interfered CDK1 expression could inhibit the proliferation of HL-60 cells and prolong the time that they enter mitosis, thereby extending the cell cycle. Compared with the control group, the overexpressed CDK1 in the pcDNA-CDK1 group made the phosphorylation level of PLK1, Aurora B, and TRF1 expression increase significantly (P<0.05), also the colony formation rate (P<0.05). The cycle-related proteins p53 and p27 was down-regulated, while cyclinA expression was up-regulate significantly (P<0.05). The results indicted that overexpressed CDK1 could stimulate adverse reactions, thereby promoting the proliferation of HL-60 cells and shortening the cell cycle.@*CONCLUSION@#Knocking out CDK1 can inhibit the phosphorylation of PLK1 and Aurora B and negatively regulate TRF1, thereby inhibiting the proliferation of leukemia cells.

Current focus issues in diagnosis and treatment of intrahepatic cholangiocarcinoma / 国际外科学杂志

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor with strong invasion and poor prognosis. ICC originates from the bile duct and locates in the liver, so it is classified as either primary liver cancer or cholangiocarcinoma, which the classification is indeterminate and the pathological typing is still debatable. The mechanism of ICC induced by many high-risk factors is still unclear. There are no characteristic manifestations in early symptom and no specific tumor markers, and the diagnosis of ICC mainly depends on imaging examination, which enhanced CT and MRI are the most important evaluation method. TNM staging of ICC is of great significance to guide the treatment, nevertheless, the division of T stage updated by AJCC 8th Edition is still controversial. Radical surgery is the only way to cure ICC currently, but there are still many controversies on definition of R0 resection and the scope of lymph node dissection. The application of local therapy and the rapid development of immunity and targeted therapy bring new hope for the transformation therapy of locally advanced patients, however, the efficacy needs to be verified by multi center large sample clinical studies. To grasp the current focus issues in diagnosis and treatment of ICC timely will be an important direction of basic and clinical research of ICC in the future.

Advances in the biosynthesis of pentostatin / 生物工程学报

Pentostatin is a nucleoside antibiotics with a strong inhibitory effect on adenosine deaminase, and is widely used in the clinical treatment of malignant tumors. However, the high cost hampers its application. In the past 10 years, the biosynthesis of pentostatin were focused on strain breeding, optimization of medium composition and fermentation process. To date, there are no reviews summarizing the elucidated biosynthetic mechanism of pentostatin. This review starts by introducing the various chemical route for production of pentostatin, followed by summarizing the mechanisms of pentostatin biosynthesis in different microorganisms. Finally, challenges for biosynthesis of pentostatin were discussed, and strategies for regulating and improving the microbial synthesis of pentostatin were proposed.

Discussion on the Quality Risk Reminder Mechanism of Drug Sampling and Testing in China / 中国药房

OBJECTIVE：To provide a reference for further improvi ng the quality risk reminder mechanism of the drug sampling and testing （called“the Reminder ”as for short ）in China ，and strengthening the drug quality management. METHODS ： The quality risk management situation of the drug sampling and testing were summarized ，and the legal nature ，main content and working procedures of the Reminder were analyzed. The latest data of the Reminder in 2020 were taken as an example to analyze the role of the Reminder in the investigation of potential drug quality risks ，and made the suggestions for existing problems. RESULTS & CONCLUSIONS ：Based on legal standards ，China’s drug regulatory departments had carried out exploratory research on drugs that may have quality and safety risks due to drug quality control blind spots or deviations of manufacturing enterprises ， and divided them into serious risks and general risks according to the severity of the problems found ，and implemented hierarchical management. The Reminder was an administrative measure for general drug quality risks based on the principle of persuasion first ， and did not have sanctions. Its main content covered all the information required for risk investigation and rectification （basic drug information， suggested risk information ， contact information ， risk discovery methods ， troubleshooting and rectification requirements，and responsibilities of local provincial drug regulatory departments ）. It involved five responsible parties ，ie. the inspection institution ，China Institute for Food and Drug Control ，National Medical Products Administration ，the provincial food and drug administration of the relevant manufacturing enterprises and the relevant manufacturing enterprises. Through the mode of closed-loop management ，the benign interaction between regulatory authorities and manufacturing enterprises could been realized. In 2020，National Medical Products Administration issued 312 reminders to 286 manufacturers，with an accuracy of 87.91％，which was scientific and targeted. The manufacturer had carried out a series of rectification measures for the contents of the Reminder ， including carrying out process verification ，revising internal control standards and strengthening production process control. However， there were also some problems ， such as the rationality of the prompt contents being questioned by the manufacturer and the i nsufficient investigation of the manufacturer. It is suggested that the manufacturers correctly understand the nature and value of the Reminder. The inspection agency should further improve the scientific pertinence of the problems found ，while the drug regulatory department should focus on the troubleshooting of the problems found ，so as to jointly promote the improvement of drug quality.

Analysis of clinical effects of iliolumbar fixation in treating U-shaped sacral fractures / 中国骨伤

OBJECTIVE@#To evaluate the efficacy of iliolumbar fixation in the treatment of U-shaped sacral fractures.@*METHODS@#A retrospective study was conducted on the 14 complex U-shaped sacral fractures which had been treated from January 2014 to December 2019, involved 10 males and 4 females, aged 24 to 48 (35.4±6.5) years. Fracture healing time, nerve function, clinical function and complications were observed in the patients.@*RESULTS@#All patients were followed up for 9 to 16(26.0±5.9) months. The complete weight-bearing time for bone healing was(12.4±2.0) weeks. One case of surgical incision infection occurred after operation, and one case of sacrum nailspenetrated to the outer plate of sacrum. No complications such as pressure ulcers, loosening or rupture of internal fixation occurred. According to Gibbons scoring, the neurological function recovered from preoperative 2.9±0.9 to postoperative 2.1±1.1, there were statistically significant differences between preoperative and postoperative (@*CONCLUSION@#Sacral lumbar fixation is an effective method for the treatment of U-shaped sacrum fractures. It has the advantages of strong internal fixation and satisfactory functional recovery.

Molecular epidemiology and virulence characteristics of polymyxin-resistant Klebsiella pneumonia / 中华传染病杂志

Objective:To analyze the molecular epidemiology and virulence characteristics of polymyxin-resistant Klebsiella pneumoniae ( K. pneumoniae). Methods:From 2011 to 2016, 1 376 strains of K. pneumoniae were isolated from various clinical specimens of hospitalized patients in First Affiliated Hospital of Wenzhou Medical University. Agar dilution method was used to screen out the polymyxin-resistant strains.Polymerase chain reaction (PCR) was used to detect the genes related to polymyxin resistance, and real-time fluorescence quantitative PCR was used to detect the relative mRNA expression level of drug resistant genes. Pulsed-field gel electrophoresis, multilocus sequence typing and Galleria mellonella larvae infection model were performed to analyze the molecular epidemiological and virulent characteristics. Results:A total of 14 strains (1.02%) of polymyxin-resistant K. pneumoniae were detected among 1 376 K. pneumoniae isolates. Subsequent sequencing identified mutations leading to amino-acid changes (K2E, F28C) in MgrB of 10 isolates and D150G in PhoQ of nine isolates, and genes such as mcr and crrB were not detected in all drug-resistant strains. Compared with standard strains, the relative expression levels of pmrH and pmrD mRNA of these drug resistant strains were increased. Analysis of the molecular epidemiology indicated that the 14 drug-resistant strains were divided into nine clones. Galleria mellonella larvae infection model revealed polymyxin-resistant K. pneumoniae isolates had higher virulence. Conclusions:Polymyxin-resistant K. pneumoniae has mutations in mgrB and phoQ genes, and mgrB mutation may play a key role in the change of virulence profiles. The homology among the polymyxin-resistant K. pneumoniae stains in this study is low.

Strategy for surgical treatment of intrahepatic cholangiocarcinoma / 国际外科学杂志

Intrahepatic cholangiocarcinoma (ICC) is a high malignant tumor, which has strong invasive, high postoperative recurrent and metastatic, and poor prognosis. Surgical resection is still the most preferred treatment for patients with ICC. The multi-disciplinary team strategy should be adopted in the treatment of ICC, which active surgery is the first choice. Radical resection and routine regional lymph node dissection with effective postoperative adjuvant therapy can improve the patient′s survival and prognosis. Neoadjuvant chemotherapy is recommended as a downstaging option for initially unresectable patients with ICC so that part of patients can obtain the opportunity of R0 resection. The recurrent ICC patients should be treated in a multidisciplinary mode.

Verification on the Developmental Toxicity of Short-term Exposure to Phenol in Rats / 生物医学与环境科学（英文）

Objective@#To verify the health advisory for short-term exposure to phenol.@*Methods@#The method of this validation experiment was the same as the US Environmental Protection Agency (EPA) methodology for toxicology experiments used to determine phenol drinking water equivalent level (DWEL). Pregnant female Sprague-Dawley rats were administered phenol in distilled water by gavage at daily doses of 15, 30, 60, 120, and 240 mg/kg body weight (b.w.) from implantation (the 6th day post-mating) to the day prior to the scheduled caesarean section (the 20th day of pregnancy). The following information was recorded: general behavior; body weight; number of corpus luteum, live birth, fetus, stillbirth, and implantation; fetal gender; body weight; body length; tail length; and abnormalities and pathomorphological changes in the dams.@*Results@#In the 60 mg/kg b.w. dose group, the mortality of pregnant rats increased with increasing doses, suggesting maternal toxicity. Fetal and placental weights decreased as phenol dose increased from 30 mg/kg b.w., and were significantly different compared those in the vehicle control group, which suggested developmental toxicity in the fetuses. However, the phenol-exposed groups showed no significant change in other parameters compared with the vehicle control group ( > 0.05).@*Conclusion@#Despite using the same method as the US EPA, a different NOEAL of 15 mg/(kg·d) was obtained in this study.

Epidemiological characteristics of pre-hospital mortality due to acute myocardial infarction from 1999 to 2016 in Tianjin city / 中华预防医学杂志

To explore the epidemiological characteristics, trends and relevant factors of pre-hospital mortality due to acute myocardial infarction (AMI) from 1999 to 2016 in Tianjin city, based on mortality surveillance information and household registration population information. Standardized mortality rates were calculated using the year 2000 world standard population. From 1999 to 2016, the research result showed that the pre-hospital crude mortality rates of AMI were 39.47/100 000 to 90.64/100 000 and the standardized mortality rates were 30.92/100 000 to 53.90/100 000. The proportion of pre-hospital AMI deaths was 73.96%-81.92% (t=1.09, P>0.05) within the same period. Aged, female, rural residents, unmarried, divorced, widowed, low education level, and outdoor workers have a relative higher proportion of pre-hospital AMI mortality.