[摘 要] 目的：探讨溶酶体相关膜蛋白3（LAMP3）与转录激活因子4（ATF4）在宫颈癌中的表达及其与临床病理参数的相关性。方法：采用免疫组化SP法检测正常宫颈组织、宫颈上皮内病变组织及宫颈癌组织中LAMP3与ATF4的表达情况，分析两种蛋白与宫颈癌患者临床病理参数之间的关系，并且分析两种蛋白的相关性。结果：LAMP3在正常宫颈组及高级别鳞状上皮内病变组中均为阴性或低表达，在宫颈癌中高表达率为38.3%，差异有统计学意义（χ2 = 14.113，P = 0.001）。ATF4在正常宫颈组中高表达率为26.7%，在高级别鳞状上皮内病变组中高表达率为10.0%，在宫颈癌组中高表达率为58.3%，差异有统计学意义（χ2 = 11.078，P = 0.004）。LAMP3的表达与宫颈癌FIGO分期（χ2 = 10.139，P = 0.006）、淋巴结转移（χ2 = 8.475，P = 0.004）有关，差异均有统计学意义。ATF4的表达在宫颈癌病灶大小（χ2 = 4.578，P = 0.032）、FIGO分期（χ2 = 8.971，P = 0.009）、淋巴结转移（χ2 = 7.881，P = 0.005）等方面的差异均有统计学意义。LAMP3与ATF4在宫颈癌中的表达呈正相关（r = 0.388，P = 0.002）。结论：LAMP3与ATF4在宫颈癌组织中表达升高，两者的表达程度具有相关性，且在宫颈癌的发生发展中发挥重要的促进作用，有望成为宫颈癌治疗的潜在靶点。

Objective:To explore the relationship between clinicopathological features, treatment and prognosis of patients with malignant mesothelioma, and provide theoretical basis for the prevention and treatment of malignant mesothelioma.Methods:In November 2022, the clinical data of 37 patients with malignant mesothelioma diagnosed in Qingdao Central Hospital from July 2014 to November 2022 were retrospectively analyzed, and the prognostic factors were analyzed by Kaplan-Meier and log-rank tests.Results:The median age of the 37 patients was 66 years old, all patients were confirmed by pathology. The median survival time of all patients was 30.00 months. The 1-year, 2-year, 3-year and 5-year cumulative survival rates were 70.27% (26/37), 48.65% (18/37), 16.22% (6/37) and 13.51% (5/37), respectively. Compared with different treatments, the median survival time of palliative care patients was 5.00 months, which was significantly lower than that of operation group (30.33 months), chemotherapy group (30.00 months), surgery combined with chemotherapy group (30.00 months) and chemotherapy combined with bevacizumab targeted therapy group (47.42 months) ( P<0.05). Gender, age (≥60 years old or <60 years old), smoking history, occupational exposure history, disease site, and surgical history were not factors affecting the survival of malignant mesothelioma patients ( P>0.05) . Conclusion:The clinical symptoms of malignant mesothelioma are not specific, but early initiation of treatment can still prolong survival, and chemotherapy combined with anti-vascular targeted therapy shows better therapeutic effect.

Objective:To explore the relationship between clinicopathological features, treatment and prognosis of patients with malignant mesothelioma, and provide theoretical basis for the prevention and treatment of malignant mesothelioma.Methods:In November 2022, the clinical data of 37 patients with malignant mesothelioma diagnosed in Qingdao Central Hospital from July 2014 to November 2022 were retrospectively analyzed, and the prognostic factors were analyzed by Kaplan-Meier and log-rank tests.Results:The median age of the 37 patients was 66 years old, all patients were confirmed by pathology. The median survival time of all patients was 30.00 months. The 1-year, 2-year, 3-year and 5-year cumulative survival rates were 70.27% (26/37), 48.65% (18/37), 16.22% (6/37) and 13.51% (5/37), respectively. Compared with different treatments, the median survival time of palliative care patients was 5.00 months, which was significantly lower than that of operation group (30.33 months), chemotherapy group (30.00 months), surgery combined with chemotherapy group (30.00 months) and chemotherapy combined with bevacizumab targeted therapy group (47.42 months) ( P<0.05). Gender, age (≥60 years old or <60 years old), smoking history, occupational exposure history, disease site, and surgical history were not factors affecting the survival of malignant mesothelioma patients ( P>0.05) . Conclusion:The clinical symptoms of malignant mesothelioma are not specific, but early initiation of treatment can still prolong survival, and chemotherapy combined with anti-vascular targeted therapy shows better therapeutic effect.

Objective:To investigate the teaching effect of blended teaching mode based on BOPPPS in the teaching of Natural Medicinal Chemistry.Methods:The undergraduate students of grade 2019 majoring in pharmacy of a medical college were selected as the research objects and divided into 2 groups randomly.Students in class 2 were set as the control group(n=27)and students in class 1 were set as the experimental group(n=29).The students of the two classes were taught by the same group of teachers.The control group adopted traditional teaching methods and classroom teaching as the main teaching mode combines with multimedia teaching.The experimental group received blended teaching mode based on BOPPPS.The final examination scores,teaching effects and student satisfaction of the two groups were compared and analyzed.Results:The survey results showed that the teaching effect of the blended teaching model based on BOPPPS was recognized by 96.55%of the students in the experimental group.The final examination score in the experimental group was higher than that in the control group(P＜0.05).The teaching effect of the experimental group was significantly better than that of the control group(P＜0.05),and the satisfaction of students in the experimental group was higher than that in the control group(P＜0.05).Conclusion:The application of blended teaching mode based on BOPPPS in the teaching of Natural Medicinal Chemistry can effectively stimulate students'learning interest and improve the teaching quality.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

BACKGROUND:Obesity has become a global health issue,often accompanied by complications including obesity-related muscle atrophy.While exercise has been reported to improve various obesity-related diseases,there is limited research focusing on exercise modes. OBJECTIVE:To compare the effects of moderate-intensity continuous training(MICT)and high-intensity interval training(HIIT)on obesity-related muscle atrophy in mice under the premise of the same exercise distance,providing a scientific basis for exercise interventions for obesity-related muscle atrophy. METHODS:Seventy-two male C57BL/6 mice were divided into six groups(n=12 per group):standard chow diet,standard chow diet+MICT,standard chow diet+HIIT,high-fat diet,high-fat diet+MICT,and high-fat diet+HIIT.The study evaluated the effects of 8-week treadmill training with different exercise modes on long-term high-fat diet-induced muscle atrophy by detecting muscle mass,muscle index,muscle fiber cross-sectional area,muscle lipid deposition,and the expression of muscle atrophy marker genes Murf-1 and Atrogin-1 in the gastrocnemius muscle of mice exposed to long-term high-fat diet. RESULTS AND CONCLUSION:Compared to the high-fat diet group,both MICT and HIIT improved the decrease in gastrocnemius muscle index(MICT+18.8%vs.HIIT+17.6%,not significant between the two modes),muscle fiber atrophy(MICT+15.5%vs.HIIT+13.7%,not significant between the two modes),and muscle lipid deposition(MICT-19.8%vs.HIIT-17.1%,not significant between the two modes).At the gene level,compared with the high-fat diet group,both MICT and HIIT could significantly down-regulate the expression of Murf-1(MICT-62.4%vs.HIIT-52.6%,the down-regulation caused by MICT was significantly greater than that by HIIT;P＜0.01)and Atrogin-1(MICT-43.3%vs.HIIT-29.8%,the down-regulation caused by MICT was significantly greater than that by HIIT;P＜0.01).Based on exercise mode comfort and genetic evidence,MICT mode might be more suitable for exercise interventions in obesity-related muscle atrophy.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Background: and Purpose X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is characterized by peripheral neuropathy with or without episodic neurological dysfunction. We performed clinical, neuropathological, and genetic investigations of a series of patients with mutations of the gap-junction beta-1 gene (GJB1) to extend the phenotypic and genetic description of CMTX1. Methods: Detailed clinical evaluations, sural nerve biopsy, and genetic analysis were applied to patients with CMTX1. Results: We collected 27 patients with CMTX1 with GJB1 mutations from 14 unrelated families. The age at onset (AAO) was 20.9±12.2 years (mean±standard deviation; range, 2–45 years). Walking difficulties, weakness in the legs, and pes cavus were common initial symptoms. Compared with female patients, males tended to have a younger AAO (males vs. females=15.4±9.6 vs. 32.0±8.8 years, p=0.002), a longer disease course (16.8±16.1 vs. 5.5±3.8 years, p=0.034), and more-severe electrophysiological results. Besides peripheral neuropathy, six of the patients had special episodic central nervous system (CNS) evidence from symptoms, signs, and/or reversible white-matter lesions. Neuropathology revealed the loss of large myelinated fibers, increased number of regenerated axon clusters with abnormally thin myelin sheaths, and excessively folded myelin. Genetic analysis identified 14 GJB1 variants, 6 of which were novel. Conclusions These findings expand the phenotypic and genetic spectrum of CMTX1. Although CMTX1 was found to have high phenotypic and CNS involvement variabilities, detailed neurological examinations and nerve conduction studies will provide critical clues for accurate diagnoses. Further exploration of the underlying mechanisms of connexin 32 involvement in neuropathy or CNS dysfunction is warranted to develop promising therapies.

Objective:To observe the efficacy and adverse reactions of fractional radiofrequency (FRF) in the treatment of facial acne scars.Methods:Fifty-seven patients with facial acne depressed scars were enrolled with the nature of Dreno scars as the diagnostic criteria. They were treated with lattice radiofrequency. The treatment heads were arranged in a matrix with a treatment area of 1.2 cm ×1.2 cm, an energy density of 80-100 mJ/pin, and an interval of five-seven once a week. And they were followed up and evaluated for the clinical efficacy and adverse reactions 6 months after the last treatment. Scoring was carried out according to the ECCA weight scores, and the efficacy judged according to complete improvement, significant improvement, moderate improvement, and mild improvement.Results:After 3 times of fractional radiofrequency treatment of 57 patients, the effective rate was 44 cases, accounting for 77.2%; the ECCA weight scores before and after treatment were 65.9±25.0 and 47.7±20.2, respectively; the difference was statistically significant ( t=13.92, P<0.001); At the same time of improvement, 32 cases of patients' complexion, fineness of pores, and skin elasticity had been improved to varying degrees, and patient satisfaction was high. Adverse reactions were mainly mild burning sensation, erythema and edema, and some patients had pale yellow exudate, etc, which could be relieved in 5-7 days. Conclusions:Fractional radiofrequency treatment of facial acne scars is safe and effective, with short recovery period, few adverse reactions and high patient satisfaction.