Research on Ethical Sensitivity of Medical Staff and Its Countermeasures: Take Pediatric Medical Staff as an Example / 中国医学伦理学

Ethical sensitivity is a behavioral concept emerging in recent years, which has attracted high attention from all sectors of society. Ethical sensitivity not only affects the clinical decision-making, doctor-patient relationship and medical quality of medical staff, but also provides the possibility to identify, predict and solve ethical problems in clinical. Combined with previous studies, this paper analyzed the current situation of ethical sensitivity of medical personnel in China, and took pediatric medical staff as an example to analyze the factors affecting the ethical sensitivity of medical staff from clinical practice and related theories, including age, working years, occupational categories, education level, work environment, empathy ability, etc. At the same time, this paper analyzed the causes of the ethical sensitivity of medical staff from the perspective of clinical practice and related systems, and put forward corresponding countermeasures, so as to improve the ethical sensitivity of medical staff and help to build a harmonious doctor-patient relationship.

Influencing Factors of Cross-cultural Communication between Medical Professionals and Patients and Ways to Improve Competence / 中国医学伦理学

In order to build a global community of health for all, it is necessary to deeply understand the influencing factors of cross-cultural communication between medical professionals and patients. Factors such as different health beliefs, cultural values and communication mediators influence cross-cultural communication between medical professionals and patients, and then affect the medical satisfaction and treatment compliance. Medical education should adopt the learning concept of constructivism, advocate maintaining a humble cultural attitude, incorporate more patient perspectives and adopt cross-cultural teaching mode to improve the cross-cultural communication competence of medical students and medical staff, so as to establish a relationship based on communication and understanding.

Effect of Xidi Liangxue recipe on the proliferation and apoptosis of HaCaT cells through the lncRNA NEAT1/miR-485-5p/STAT3 regulatory network / 中华皮肤科杂志

Objective:To investigate the effect of Xidi Liangxue recipe on the proliferation and apoptosis of HaCaT cells through the long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) /microRNA (miR) -485-5p/signal transducer and activator of transcription 3 (STAT3) regulatory network. Methods:HaCaT cells were induced by interleukin-17 (IL-17), and the mRNA and protein expression of lncRNA NEAT1, miR-485-5p and STAT3 was detected in IL-17-induced HaCaT cells and normal human epidermal keratinocytes (NHEK) by quantitative PCR (qPCR) and Western blot analysis, respectively. The location of lncRNA NEAT1 and miR-485-5p in IL-17-induced HaCaT cells was observed by fluorescence in situ hybridization (FISH), and the targeted regulatory relationship among lncRNA NEAT1, miR-485-5p and STAT3 was verified by double-luciferase reporter gene assay. Chinese herbs were decocted according to the Xidi Liangxue recipe, SD rats were divided into two groups to be gavaged with the above decoctions (medicated group) or physiological saline (control group) for 5 days, and then serum samples were collected from the above two groups of rats separately. The IL-17-induced HaCaT cells were divided into 4 groups: control group treated with the control sera, lncRNA-NEAT1 overexpression group transfected with lncRNA-NEAT1 overexpression vectors and treated with the control sera, Xidi Liangxue recipe group treated with the medicated sera, and Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group transfected with lncRNA-NEAT1 overexpression vectors and treated with the medicated sera. qPCR, Western blot analysis, flow cytometry, and cell counting kit (CCK8) assay were performed to determine the mRNA and protein expression of lncRNA NEAT1, miR-485-5p and STAT3, and to evaluate cell proliferation and apoptosis. The two independent samples t-test was used for comparisons between two groups, one-way analysis of variance for comparisons among multiple groups, and least significant difference (LSD) t-test for multiple comparisons. Results:The IL-17-induced HaCaT cell group showed significantly increased relative expression levels of lncRNA NEAT1 and STAT3 mRNA (1.84 ± 0.21, 2.20 ± 0.24, respectively) and significantly increased protein expression of STAT3 and p-STAT3 (1.27 ± 0.13, 2.43 ± 0.16, respectively), but significantly decreased expression level of miR-485-5p (0.32 ± 0.04) compared with the NHEK group (lncRNA NEAT1 and STAT3 mRNA: 1.00 ± 0.11, 1.00 ± 0.11, respectively, both P < 0.05; STAT3 and p-STAT3 protein: 1.00 ± 0.11, 1.00 ± 0.10, t = 2.54, 3.02, respectively, both P < 0.05; miR-485-5p: 1.00 ± 0.12, t = 2.94, P = 0.015). FISH demonstrated that miR-485-5p and lncRNA NEAT1 were co-located in the cytoplasm of HaCaT cells. The double-luciferase reporter gene assay showed that the relative activity of luciferase was significantly lower in the miR-485-5p group than in the negative control group (both P < 0.05) after the transfection with wild-type lncRNA NEAT1 or STAT3 recombinant plasmids, while there were no significant differences between the miR-485-5p group and negative control group after the transfection with mutant lncRNA NEAT1 or STAT3 recombinant plasmids (both P > 0.05). Compared with the control group, the lncRNA-NEAT1 overexpression group showed significantly increased expression of lncRNA NEAT1 and STAT3 (including STAT3 mRNA, STAT3 protein, and p-STAT3 protein) in HaCaT cells (all P < 0.05), but significantly decreased miR-485-5p expression ( P < 0.05) ; the Xidi Liangxue recipe group showed significantly decreased expression of lncRNA NEAT1 and STAT3 (all P < 0.05), but significantly increased miR-485-5p expression compared with the control group ( P < 0.05) ; significantly decreased expression of lncRNA NEAT1 and STAT3, but significantly increased miR-485-5p expression was observed in the Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group compared with the lncRNA-NEAT1 overexpression group (all P < 0.05). After 24-, 48-, and 72-hour intervention, CCK8 assay showed that the proliferative activity of HaCaT cells was significantly higher in the lncRNA-NEAT1 overexpression group than in the control group (all P < 0.05), as well as in the Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group than in the Xidi Liangxue recipe group (all P < 0.05), and the cellular proliferative activity was significantly lower in the Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group and Xidi Liangxue recipe group than in the control group (all P < 0.05). The apoptosis rate was significantly lower in the lncRNA-NEAT1 overexpression group (5.84% ± 0.28%) than in the control group (14.75% ± 0.83%, LSD- t = 3.48, P = 0.002), but significantly higher in the Xidi Liangxue recipe group (35.72% ± 3.62%) than in the control group (LSD- t = 5.34, P = 0.001) ; the Xidi Liangxue recipe + lncRNA-NEAT1 overexpression group showed significantly increased apoptosis rate (27.64% ± 2.82%) compared with the lncRNA-NEAT1 overexpression group (LSD- t = 9.06, P < 0.001) . Conclusion:The Xidi Liangxue recipe could inhibit the proliferation of IL-17-induced HaCaT cells and promote their apoptosis, which may be related to the intervention in the lncRNA NEAT1/miR-485-5p/STAT3 regulatory network.

The construction and thinking of the online open course of Knowledge and Skills of Health Education for the Army / 中华医学教育探索杂志

Military vocational education has become one of the strategies to strengthen the military in the new era. The army urgently needs to build a number of featured online courses of military vocational education. Therefore, taking the course "Knowledge and Skills of Health Education for the Army" as an example, this paper discusses the overall construction objectives, construction ideas, teaching content, curriculum and test question bank construction of the course. In addition, this paper analyzes and summarizes the problems existing in the teaching organization, implementation, and preliminary application, so as to provide ideas and construction strategies for the construction of online open courses in other military vocational education.

Effect of Ganmai Dazao Decoction on ethology of rats with PTSD and its mechanism / 中国中药杂志

This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.

Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version) / 中国中药杂志

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Extracellular Signal-regulated Kinase 1/2 Signaling Regulates Cell Invasion:a Review / 中国医学科学院学报

Extracellular signal-regulated kinase 1/2 (ERK1/2) is a serine/threoninekinase involved in the signal transduction cascade of Ras-Raf-mitogen-activated protein kinase (MEK)-ERK.It participates in the cell growth,proliferation and even invasion by regulating gene transcription and expression.The occurrence of a variety of diseases such as lung cancer,liver cancer,ovarian cancer,cervical cancer,endometriosis,and preeclampsia,as well the metastasis and disease progression,is closely associated with the regulation of cell invasion by ERK1/2 signaling pathway.Therefore,exploring the regulation of ERK1/2 signaling on cell invasion and its role in pathogenesis of diseases may help to develop more effective treatment schemes.This article introduces recent progress in the regulation of ERK1/2 signaling on cell invasion and the role of such regulation in diseases,with a view to give new insights into the clinical treatment of ERK 1/2-related diseases.

Prognostic Value of CD56 Expression in Newly Diagnosed Multiple Myeloma Patients and Its Related Factors / 中国实验血液学杂志

OBJECTIVE@#To analyze the effect of CD56 expression on the prognosis of newly diagnosed multiple myeloma (MM) patients and explore the relationship between CD56 with clinical characteristics.@*METHODS@#In this retrospective study, the clinical data and laboratory parameters of 175 newly diagnosed MM patients from February 2015 to December 2020 in the Second Hospital of Anhui Medical University were collected. The patients were divided into CD56+ and CD56- groups based on the expression of CD56, and the general data and laboratory parameters of the two groups were compared. The patients were followed up to June 30, 2021, and progression-free survival (PFS) and overall survival (OS) were recorded. PFS and OS curves of the two groups were plotted respectively, and the survival differences were compared. Univariate and multivariate Cox regression analyses were performed to analyze the effect of CD56 on the prognosis of newly diagnosed MM patients.@*RESULTS@#In 175 newly diagnosed MM patients, 57(32.6%) cases were in the CD56-group and 118 (67.4%) cases in the CD56+ group. There was significant correlation between CD56 expression and ISS stage, ECOG score, platelets, β2-microglobulin, creatinine, and extramedullary disease (all P <0.05). The incidence of extramedullary disease in the CD56- group was significantly higher than that in the CD56+ group (29.8% vs 12.7%, P =0.006). The median follow-up time of the whole cohort was 23.6 (1.0-78.6) months. The median PFS of patients in CD56+ group and CD56- group were 18.6 (1.2-77.6) and 12.2 (1.0-49.0) months, respectively, and the median OS of the two groups were 27.6 (1.4-77.7) and 19.7 (1.0-78.6) months, respectively. The 2-year PFS rate in the CD56+ group was significantly higher than that in the CD56- group (57.6% vs 36.8%, P =0.010), and the 2-year OS rate in the CD56+ group was higher than that in the CD56- group, but it didn't reach statistical significance (74.6% vs 64.9%, P =0.158). The results of univariate Cox regression analysis showed that the PFS was significantly shorter in newly diagnosed MM patients with advanced age, type IgG, high ECOG score, decreased platelet count, increased lactate dehydrogenase level, extramedullary disease, and CD56- (all P <0.05), the OS was significantly shorter in patients with high ECOG score, decreased platelet count, increased lactate dehydrogenase level, extramedullary disease, and CD56- (all P <0.05). The results of multivariate Cox regression analysis showed that advanced age, type IgG, elevated lactate dehydrogenase level, extramedullary disease, and CD56- were independent prognostic factors for poor PFS (all P <0.05); and decreased platelet count, elevated lactate dehydrogenase level, and extramedullary disease were independent adverse prognostic factors for OS (all P <0.05), while there was no significant independent correlation between CD56 and OS (P >0.05).@*CONCLUSION@#Most of the newly diagnosed MM patients have positive expression of CD56. Loss of CD56 expression was associated with unfavorable biological and clinical parameters and poor prognosis, suggesting that CD56 has important clinical value in the prognosis of newly diagnosed MM patients.

DJ1 Ameliorates AD-like Pathology in the Hippocampus of APP/PS1 Mice / 生物医学与环境科学（英文）

OBJECTIVE@#To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD.@*METHODS@#Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 +), and DJ1-knockdown group (DJ1 -). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice.@*RESULTS@#DJ1 + overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 - cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 + increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA).@*CONCLUSION@#DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.

Effects of acute normovolemic hemodilution combined with intraoperative recycled autotransfusion on blood transfusion volume and coagulation function in elderly patients undergoing cardiac surgery / 中国输血杂志

【Objective】 To explore the effects of acute normovolemic hemodilution (ANH) combined with intraoperative recycled autotransfusion on blood transfusion volume and coagulation function in elderly patients undergoing cardiac surgery. 【Methods】 A total of 94 elderly patients undergoing cardiac surgery in the hospital were enrolled and randomly divided into observation group (n=47) and control group (n=47) between March 2020 and March 2022. The observation group was given ANH combined with intraoperative recycled autotransfusion, while control group was given routine allogeneic transfusion. The blood transfusion volume, oxygenation status, immune function, inflammatory indexes and adverse reactions in the two groups were compared. 【Results】 The banked blood transfusion volume was less in observation group than control group [(1.73±0.43) U vs (5.71±1.71) U, P<0.05]. At 6 h after surgery, blood oxygen saturation (SvO2) level was higher [(74.59±7.20) % vs (67.22±6.19) %], while oxygen uptake rate (ERO2) level was lower[(0.29±0.06) % vs (0.34±0.05) %] in observation group than control group (P<0.05). At day 1 after surgery, levels of CD3+, CD4+, CD4+ /CD8+ and natural killer cells (NK) were higher [(65.11±5.14) %, (46.93±5.17) %, (1.86±0.30), (8.35±1.23) % vs (57.45±7.24) %, (43.58±4.85) %, (1.47±0.36)%, (7.34±1.38) %], while CD8+ was lower [(25.17±4.01) % vs (30.39±5.06) %] in observation group than control group (P<0.05). At day 1 after surgery, levels of serum interleukin 6/8 (IL-6/8) and tumor necrosis factor-α (TNF-α) were lower in observation group than control group [(104.51±12.55) ng/L vs (125.81±14.96) ng/L, (351.42±52.86) ng/L vs (394.27±55.78) ng/L, (254.93±49.94) ng/L vs (323.60±52.63) ng/L, P<0.05]. The incidence of adverse reactions was lower in observation group than control group (4.26% vs 17.02%), P<0.05. 【Conclusion】 Recycled autotransfusion can reduce allogeneic transfusion volume in elderly patients undergoing cardiac surgery. There is no difference in the effects on blood routine or coagulation function between recycled autotransfusion and allogeneic transfusion. Compared with allogeneic transfusion, recycled autotransfusion can significantly improve oxygenation status, relieve immunosuppression and inflammation response, and reduce the risk of adverse reactions.

Genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021 / 中华预防医学杂志

Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.

Children parents attitude and demand towards family based child sexual abuse prevention education / 中国学校卫生

Objective@#To investigate the attitudes and demands of parents of children in Luzhou towards family based child sexual abuse prevention education.@*Methods@#A self administered anonymous questionnaire survey was conducted among parents of children in Luzhou City who were selected from stratified cluster sampling. Multiple linear regression model was used to analyze parents attitudes.@*Results@#Parents attitude towards prevention of sexual assault education was positive (average score 16.70± 3.67 ). The results of multiple regression analysis showed that parents of only child ( β =0.30), parents who participated in related activities ( β =1.28), communicated with relatives and friends ( β =0.81), and lived in urban areas ( β =0.49) had more positive attitudes. In terms of parental factors, average annual family income higher than 100 000 yuan ( β =0.39), mothers of young children ( β =0.88), and parents with a high level of knowledge about sexual assault prevention education ( β =0.98), the mother being a teacher or a medical staff ( β =0.52), and educational background of the mother being high school/secondary school ( β =1.03), college/undergraduate or above ( β =1.42) were associated with more positive attitudes( P <0.01). The results of demand analysis showed that parents had high demand for child s self protection (96.86%).@*Conclusion@#Parents of young children in Luzhou City show generally positive attitude and high demand towards family based sexual abuse prevention. Knowledge training and publicity regarding child sexual abuse should be improved for children who had siblings, from rural and township areas, and whose parents with low educational background.

The biological principle of "Biao Ben Jian Zhi" / 药学学报

Along with the progress of pharmaceutical science in the past century, the theme of pharmacology has gone through pseudo agent scheme, to ligand-receptor model, and then to the theory of targeted therapy today. Due to the success of drug R&D, current drug research keeps its focus mainly on drugs with single target and precise treatment, in which the molecular mechanism is relatively clear but the therapeutic efficacy is often limited. Thus, there is a big space for exploration in the field of pharmacology. In the past 30 years, several novel chemical drugs, originated from traditional Chinese medicine, have been identified and then used in clinic, provoking a strong interest to explore new theory for pharmacology, of which the term of "Biao Ben Jian Zhi" (treating diseases by directing symptoms and root causes) has demonstrated a promising nature. We consider this concept useful for future drug discovery, drug design and clinical therapy. In this review, example drugs such as berberine, metformin and azvudine, are discussed, and "drug Cloud" (dCloud) model is introduced to elaborate the mechanism of treating diseases by directing symptoms and root causes of diseases.

Advances in the study of new BCR-ABL kinase inhibitors / 药学学报

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

Effects of intranasal administration of tripterygium glycoside-bearing liposomes on behavioral cognitive impairment of mice induced by central nervous system inflammation / 中国中药杂志

Tripterygium glycosides liposome(TPGL) were prepared by thin film-dispersion method, which were optimized accor-ding to their morphological structures, average particle size and encapsulation rate. The measured particle size was(137.39±2.28) nm, and the encapsulation rate was 88.33%±1.82%. The mouse model of central nervous system inflammation was established by stereotaxic injection of lipopolysaccharide(LPS). TPGL and tripterygium glycosides(TPG) were administered intranasally for 21 days. The effects of intranasal administration of TPG and TPGL on behavioral cognitive impairment of mice due to LPS-induced central ner-vous system inflammation were estimated by animal behavioral tests, hematoxylin-eosin(HE) staining of hippocampus, real-time quantitative polymerase chain reaction(RT-qPCR) and immunofluorescence. Compared with TPG, TPGL caused less damage to the nasal mucosa, olfactory bulb, liver and kidney of mice administered intranasally. The behavioral performance of treated mice was significantly improved in water maze, Y maze and nesting experiment. Neuronal cell damage was reduced, and the expression levels of inflammation and apoptosis related genes [tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), BCL2-associated X(Bax), etc.] and glial activation markers [ionized calcium binding adaptor molecule 1(IBA1) and glial fibrillary acidic protein(GFAP)] were decreased. These results indicated that liposome technique combined with nasal delivery alleviated the toxic side effects of TPG, and also significantly ameliorated the cognitive impairment of mice induced by central nervous system inflammation.

Wernekink Commissure Syndrome With Hallucinations and Involuntary Groping:Report of One Case / 中国医学科学院学报

Wernekink commissure syndrome is a rare midbrain syndrome with bilateral cerebellar dysfunction,eye movement disorder,and palatal myoclonus.Few cases of this syndrome have been reported in China,let alone those combined with hallucinations and involuntary groping.This paper reports the diagnosis and treatment of a case of Wernekink commissure syndrome with hallucinations and involuntary groping,aiming to enrich the knowledge about this disease for clinicians.

Exploration on ALT threshold for initiating antiviral therapy in chronic HBV-infected patients based on results of 707 liver puncture cases / 中国热带医学

@#Abstract: Objective To explore the threshold of ALT for initiating antiviral therapy in HBV infected patients, and to provide a basis for initiating antiviral therapy in chronic HBV-infected patients. Methods This retrospective cohort study recruited 707 consecutive treatment-naïve chronic hepatitis B (CHB) patients undergoing diagnostic liver biopsy in the department of infectious diseases of the Affiliated Hospital of Yan′an University from October 2013 to August 2018. Liver biopsy specimens were obtained under ultrasound guidance using Menghini 16G disposable needles. The METAVIR scoring system, which is commonly used internationally, was used to divide the patients into the group with mild liver tissue injury and the group with significant liver tissue injury, and the alanine aminotransferase (ALT) levels were measured separately. Receiver operating characteristic (ROC) curve and Mann-Whitney U test were used to evaluate the diagnostic value of ALT for significant liver tissue injury under different demographic characteristics. Results Of 707 patients, 292 (41.30%) had significant liver tissue injury confirmed by liver biopsy (METAVIR ≥A2 and/or F2). When the ULN of ALT was set to NICE criteria (30 U/L for males, 19 U/L for females), AASLD criteria (35 U/L for males, 25 U/L for females) and EASL or APASL criteria (40 U/L for males and females), CHB patients with <ULN accounted for 32.38%, 35.03% and 36.07% of significant liver tissue injury, respectively. And significant liver tissue injury in CHB patients with 1-2×ULN accounted for 41.99%, 41.85% and 50.30%, respectively. The optimal ALT critical values were 33 U/L for overall patients, 25 U/L for females, 45 U/L for males, 45 U/L for ≤30 years olds, 33 U/L for>30 years olds, 22 U/L for HBeAg negative and 31 U/L for HBeAg positive patients. Conclusions The threshold of ALT for initiating antiviral therapy in chronic HBV patients should be individualized, especially should be down-regulated for the females, olders and HBeAg-negative patients.

Rapid prediction of G protein-coupled receptor structures using nanoluciferase assay / 药学学报

Using beta-2 adrenergic receptor, 5-hydroxytryptamine and angiotensin II type 1 receptor as control, we here established a method for rapid prediction of the initial position amino acids of N-terminal, C-terminal, intracellular loops, extracellular loops and transmembrane (TM) regions in G protein-coupled receptors (GPCRs), and successfully predicted the structure of Mas-related G protein-coupled receptors X3 (MRGPRX3). To achieve this purpose, nanoluciferase (Nluc) was inserted into the different sites of these GPCRs′ sequence by sequence and ligation-independent cloning (SLIC) method, and the luminescence value were measured to distinguish the different parts of GPCRs. The results showed that luminescence values of NLuc luciferase at TM region were less than 100 000, and the values were higher than 1 000 000 at N terminal, C terminal, or extracellular loops and intracellular loops, and the values were between 100 000 and 500 000 at junction. The predicted MRGPRX3 structure was analyzed in detail and was compared with AlphaFold predicted structure. In conclusion, this method could provide useful information of GPCR structure model for the ligand virtual screening, and could provide certain experimental basis for structural pharmacology.

Long-term trend analysis of liver cancer survival rate in Qidong region, Jiangsu Province, 1972-2019 / 中华肝脏病杂志

Objective: To analyze the incidence and survival rate of liver cancer cases in the entire population in the Qidong region from 1972 to 2019, so as to provide a basis for prognosis evaluation, prevention, and treatment. Methods: The observed survival rate (OSR) and relative survival rate (RSR) of 34 805 cases of liver cancer in the entire Qidong region population from 1972 to 2019 were calculated using Hakulinen's method with SURV3.01 software. Hakulinen's likelihood ratio test was used for statistical analysis. Age-standardized relative survival (ARS) was calculated using the International Cancer Survival Standard. The Joinpoint regression analysis was performed with Joinpoint 4.7.0.0 software to calculate the average annual percentage change (AAPC) of the liver cancer survival rate. Results: 1-ASR increased from 13.80% in 1972-1977 to 50.20% in 2014-2019, while 5-ASR increased from 1.27% in 1972-1977 to 27.64% in 2014-2019. The upward trend of RSR over eight periods was statistically significant (χ (2) = 3045.29, P < 0.001). Among them, male 5-ASR was 0.90%, 1.80%, 2.33%, 4.92%, 5.43%, 7.05%, 10.78%, and 27.78%, and female 5-ASR was 2.33%, 1.51%, 3.35%, 3.92%, 3.84%, 7.18%, 11.45%, and 29.84%, respectively. There was a statistically significant difference in RSR between males and females (χ (2) = 45.68, P < 0.001). The 5-RSR for each age group of 25-34 years old, 35-44 years old, 45-54 years old, 55-64 years old, 65-74 years old, and 75 years old were 4.92%, 5.29%, 8.17%, 11.70%, 11.63%, and 9.60%, respectively. There were statistically significant differences in RSR among different age groups (χ (2) = 501.29, P < 0.001). The AAPC in Qidong region from 1972 to 2019 for 1-ARS, 3-ASR, and 5-ARS were 5.26% (t = 12.35, P < 0.001), 8.10% (t = 15.99, P < 0.001), and 8.96 % (t = 16.06, P < 0.001), respectively. The upward trend was statistically significant in all cases. The AAPC of 5-ARS was 9.82% in males (t = 14.14, P < 0.001), and 8.79% in females (t = 11.48, P < 0.001), and the upward trend was statistically significant in both. The AAPC of 25-34 years old, 35-44 years old, 45-54 years old, 55-64 years old, 65-74 years old, and 75 years old were 5.37% (t = 5.26, P = 0.002), 5.22% (t = 5.66, P = 0.001), 7.20% (t = 6.88, P < 0.001), 10.00% (t = 12.58, P < 0.001), 9.96% (t = 7.34, P < 0.001) and 8.83% (t = 3.51, P = 0.013), and the upward trend was statistically significant. Conclusion: The overall survival rate of registered cases of liver cancer in the Qidong region's entire population has greatly improved, but there is still much room for improvement. Hence, constant attention should be paid to the study on preventing and treating liver cancer.

Establishment of PCR assays and genetic polymorphism analysis of genes encoding Clostridium perfringens β2 toxin from different sources / 中华流行病学杂志

Objective: To establish and optimize PCR methods for the gene encoding of Clostridium perfringens β2 toxin (cpb2) and atypical-cpb2 (aty-cpb2), analyze the epidemiological characteristics and genetic polymorphism of the cpb2 of Clostridium perfringens in 9 Chinese areas from 2016 to 2021. Methods: The cpb2 of 188 Clostridium perfringens strains were examined by PCR; the cpb2 sequences were acquired by whole-genome sequencing to analyze the genetic polymorphism. Using Mega 11 and the Makeblastdb tool, a phylogenetic tree, and cpb2-library based on 110 strains carrying the cpb2 were produced. Using the Blastn technique, a comparison was made to discover sequence similarity between consensus-cpb2 (con-cpb2) and aty-cpb2. Results: The specificity of PCR assay for the cpb2 and aty-cpb2 was verified. The PCR results for cpb2 amplification were highly consistent with the whole-genome sequencing approach (Kappa=0.946, P<0.001). A total of 107 strains from nine regions in China carried cpb2, 94 types A strains carried aty-cpb2, 6 types A strains carried con-cpb2, and 7 types F strains carried aty-cpb2. The nucleotide sequence similarity between the two coding genes was 68.97%-70.97%, and the similarity between the same coding genes was 98.00%-100.00%. Conclusions: In this study, a specific PCR method for cpb2 toxin was developed, and the previous PCR method for detecting aty-cpb2 was improved. aty-cpb2 is the primary gene encoding of β2 toxin. There is a significant nucleotide sequence variance between the various cpb2 genotypes.