Interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes / 中国药房

OBJECTIVE To study the interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes. METHODS In vitro ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1，8-cineole （0.25， 0.5 μmol/L） on the level of Fe2+ in pancreatic β cells were investigated. The effects of 1，8-cineole （0.5 μmol/L） combined with ferroptosis inducer Erastin （20 μmol/L） and ferroptosis inhibitor Ferrostatin-1 （20 μmol/L） on the protein expressions of glutathione peroxidase-4 （GPX4） and cyclooxygenase-2 （COX2） were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1，8-cineole （50， 200 mg/kg） on the pathological morphology of pancreatic tissue， the content of iron as well as the protein expressions of GPX4 and COX2 were investigated. RESULTS The results of the cell experiment showed that compared with the model group， pretreatment with 1，8-cineole significantly reduced intracellular Fe2+ levels and upregulated GPX4 protein expression， while downregulated COX2 protein expression in pancreatic β cells （P＜0.05）. After combining with Ferrostatin-1， the expression trends of the above two proteins were the same， while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group， after intervention with 1，8-cineole， the structure of the pancreatic islets in mice recovered intact and their morphology improved； the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly （P＜0.05）， while protein expression of GPX4 was increased significantly （P＜0.05）. CONCLUSIONS 1，8-cineole could ameliorate pancreatic β cell injury induced by diabetes， the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.

Quality evaluation of Chinese and global guidelines/consensus for TDM of anti-TNF-α agents in patients with inflammatory bowel disease / 中国药房

OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring （TDM） of anti-tumor necrosis factor-α （TNF-α） in patients with inflammatory bowel disease （IBD） in China and globally. METHODS PubMed， Embase， CNKI， Wanfang data， VIP， and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data， the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included， 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions （scope and aims， participants， rigor of formulation， clarity of expression， application， and editorial independence） were 90.43%， 41.98%， 52.55%， 85.49%， 19.00%， and 76.85%， respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios， threshold ranges， strategy adjustments， detection methods， and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally， the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair， with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs， and interpret and apply results of TDM in combination with specific clinical treatment goals.

Association between exposure to multiple metals and lung function in welders by multi-pollutant statistical models / 环境与职业医学

Background Welders' exposure to welding fumes with multiple metals leads to decreased pulmonary function. Previous studies have focused on single metal exposure, while giving little attention to the impact of metal mixtures. Objective To assess the association between metal levels in urine and blood of welders and pulmonary function indicators, and to identify key metals for occupational health risk assessment. Methods Questionnaire surveys, lung function tests, urine and blood sampling were conducted among welders and control workers in a shipyard in Shanghai. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the concentrations of 12 metals such as vanadium, chromium, and manganese in urine and blood. Spearman correlation was applied to analyze the correlations between the metals in urine and blood. Multiple linear regression, weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) were used to analyze the relationships between mixed metal exposure and pulmonary function parameters, such as forced vital capacity (FVC), forced vital capacity as a percentage of predicted value (FVC%), forced expiratory volume in the first second (FEV1), forced expiratory volume in the first second as a percentage of predicted value (FEV1%), and forced expiratory volume in the first second/forced vital capacity (FEV1/FVC). Results This study enrolled 445 subjects, including 322 welders (72.36%) and 123 controls (27.64%). The mean age of the 445 participants was (37.64±8.80) years, and 87.19% participants were male. The welders had significantly higher levels of urinary cadmium (0.88 vs 0.58 μg·L−1), blood chromium (5.86 vs 5.06 μg·L−1), and blood manganese (24.24 vs 21.38 μg·L−1) than the controls (P<0.05). The Spearman correlation coefficients between the metals in urine and blood ranged from −0.46 to 0.68. After adjustment for confounders, the multiple linear regression indicted that the urine molybdenum of the welders was negatively correlated with FVC and FEV1. There were also negative correlations between the molybdenum in blood and FVC, FVC%, FEV1, and FEV1%, and between the copper in blood and FEV1/FVC. The WQS model showed that FEV1 and FVC decreased by 0.112 L and 0.353 L with each quartile increase of metal mixture concentrations in urine and blood among the welders respectively, and the leading contributors were copper, zinc, vanadium, and antimony. The BKMR model showed a negative overall effect of metal mixtures in urine and blood among the welders on FVC, FVC%, FEV1, and FEV1%, and the univariate exposure response-relationship between the molybdenum concentration in urine or blood and FVC, FVC%, FEV1, or FEV1% had an approximately linear decreasing trend. Meanwhile, there may be an interaction of cadmium with manganese, nickel, or vanadium, and an interaction of vanadium with iron, molybdenum, zinc, or copper, when different metals in urine among the welders interacted with FEV1%. Conclusion Exposure to multiple metals in welders leads to a decline in lung function, with molybdenum, antimony, copper, and zinc as the leading contributors.

Circumlimbal suture and laser burns:Comparison between two different chronic glaucoma models / 中南大学学报(医学版)

Objective:Glaucoma is a multifactorial optic neuropathy with a high rate of irreversible visual loss,and its pathogenesis is complex and still unclear.Elevated intraocular pressure(IOP)is well recognized as the sole modifiable risk factor for the development of glaucoma in the majority of cases.This study aims to compare 2 different methods of inducing chronic ocular hypertension by circumlimbal suture or by laser burns in degree and lasting time of the IOP,different status of the retina and retinal ganglion cells(RGCs),and changes of the microstructure of neurons. Methods:The chronic ocular hypertension models were induced by 2 different ways.One kind of the models was built by unilateral circumlimbal suture(10/0)implantation(suture group),another kind of model was built by laser burns at trabecular meshwork and episcleral veins(laser group).The untreated contralateral eye served as the control group.Changes in IOP were observed and regularly monitored in the 2 groups of rats.HE staining was applied to observe the retinal and optic nerve pathology.Transmission electron microscope(TEM)was used to observe the mitochondrial morphology.RGCs were specifically labeled with Brn3b antibody and counted.The expression of caspase-3 was detected by Western blotting to clarify the apoptosis of RGCs. Results:Compared with the control group,IOP were significantly increased in the suture group and the laser group(both P<0.05).The suture group induced a 1.5-fold elevation of IOP,and sustained for 8 weeks.The laser group induced a 2-fold elevation of IOP for 12 weeks.Both methods could cause RGCs loss(both P<0.05),which were verified by pathology and immune staining of Brn3b.The expressions of caspase-3 were also increased(both P<0.05).The mitochondrial morphology became more fragment,which changed from long shape to round and small one under TEM in 2 models.For comparison,the pathology changes of retinal structure in suture group were not obviously than those in the laser group. Conclusion:Circumlimbal suture can build an effective model of chronic elevated IOP and induce glaucomatous pathologic changes similar to those in the laser photocoagulation,but the pathologic changes are milder than those in laser photocoagulation.Compare with translimbal laser photocoagulation,equipment and skill demand for circumlimbal suture is less.

Nucleophosmin acetylation and construction and expression of its modified sites mutants in breast cancer / 解剖学报

Objective To determine the acetylation level of nucleophosmin(NPM)in female breast cancer and to discuss its function through mutation of modified lysine sites.To construct positive and negative NPM mutants on its acetylated lysine sites and to express them in breast cancer cells.Methods Acetylation level and acetylated lysine sites of NPM in three breast cancer tissues and para-carcinoma tissues were detected by acetylome technology;NPM mutants were constructed by site-directed mutagenesis PCR,specific PCR products were digested by DpnI and transformed into Escherichia coli(E.coli)to obtain specific plasmids for mutants;The accuracy of mutants were verified by double restriction enzyme digestion and sequencing;The mutants were expressed in BT-549 cells by transient transfection and verified by RT-PCR method.Protein expression and acetylation level of NPM were validated by Western blotting;Function of NPM acetylation was analyzed by proteomic detection and bioinformatic analysis.Results The 27th and 32nd lysine of NPM were highly acetylated in breast cancer tissues,which were 2.76 and 2.22 times higher than those in adjacent normal tissues,respectively;The NPM mutants showed the same molecular weight as that of wild type NPM and contained expected mutation sites;Corresponding NPM mRNA levels of BT-549 cells transfected with NPM mutants were significantly increased.With the increase of wild type NPM expression level,NPM acetylation level increased,while decreased after 27th lysine underwent negative mutation.NPM acetylation can significantly change the expression levels of 101 proteins in BT-549 cells,which are enriched in regulation of cellular macromolecule biosynthesis,DNA-template transcription,RNA biosynthesis and RNA metabolism process.Conclusion NPM is highly acetylated in breast cancer and can play a key role in cellular macromolecule biosynthesis,DNA-templated transcription,RNA biosynthesis and RNA metabolism process.

Application and progress of cyclosporine A in ocular surface diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Cyclosporine A, a cyclic polypeptide, exhibits potent immunosuppressive activity and exerts its effects through various mechanisms including immunosuppression, anti-inflammatory, inhibition of apoptosis, promotion of epithelial healing and goblet cell function recovery, enhancement of tear secretion, and close association with ocular surface disease repair. Owing to its significant efficacy, inhibition of disease recurrence and few side effects, the clinical application of cyclosporine A in the management of ocular surface diseases, including dry eye, corneal graft rejection following penetrating keratoplasty, vernal keratoconjunctivitis, noninfective keratitis and herpes simplex virus keratitis, has witnessed a substantial rise in recent years. Nevertheless, variations exist in the management of ocular surface inflammatory diseases when utilizing distinct concentrations and dosage forms of cyclosporine A. Therefore, the paper provides an overview of impacts of cyclosporine A on ocular surface diseases.

A Practical Randomized Controlled Study on Effectiveness of TCM Syndrome Differentiation Treatment for Subsolid Pulmonary Nodules / 肿瘤防治研究

Objective To explore the therapeutic effect of traditional Chinese medicine (TCM) on subsolid nodule (SSN). Methods A practical randomized controlled study method, including 254 SSN patients was adopted. The patients were divided into the TCM (102 cases) and follow-up (152 cases) groups. The follow-up group received regular check-ups in accordance with the guidelines, and the TCM group received TCM syndrome differentiation treatment for 24 weeks. The two groups were compared in terms of the changes in their SSN diameter, SSN number, TCM symptom score, and overall therapeutic effect before and after treatment. Adverse reactions and safety indicators were also recorded. Results The TCM group showed a significantly higher effective rate of treatment (16.7%) than the follow-up group (2.6%) (P<0.01). Compared with their condition before treatment, the TCM group showed no significant changes in their SSN diameter and number but presented considerably reduced fatigue, yellow and red urine symptoms, and overall TCM symptom score (P<0.05). The follow-up group exhibited significantly increased diameter and number of SSN (P<0.01). The follow-up group showed the significantly higher increase in SSN diameter after treatment than the TCM group (P<0.05). Moreover, the follow-up group showed significantly higher fatigue, depression, yellow and red urine symptom scores, and overall TCM symptom score than the TCM group (P<0.05 or P<0.01). Conclusion TCM treatment for SSN has a distinct clinical efficacy, reduces the malignant risk of SSN and improves clinical symptoms of SSN patients, and is safe and feasible.

Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors / 药学学报

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

miRNA derived from mesenchymal stem cells and its derivatives in treatment of pathological scar / 中国组织工程研究

BACKGROUND:Stem cell therapy has become an emerging method of treating pathological scars.miRNAs are involved in scarring mechanisms,and the targeted action of some stem cell sources of miRNA is mediated by exosomes. OBJECTIVE:To review the biological properties of miRNA derived from mesenchymal stem cells and its derivatives,the mechanism of treatment of scarring through anti-inflammation,suppression of excessive tissue reconstruction and antioxidation. METHODS:The first author used a computer in September 2023 to retrieve the relevant literature published from January 2000 to September 2023,searching for"stem cell,exosome,miRNA,keloid"in English,and"stem cells,exosome,keloid"in Chinese,eventually incorporating 74 papers for analysis. RESULTS AND CONCLUSION:(1)miRNAs with high expression of exosomes derived from mesenchymal stem cells increase the proportion of M2-type macrophages by promoting the polarization of macrophages,target the regulation of transforming growth factor β,transforming growth factor β receptors or related signaling pathways,inhibit the expression of pro-inflammatory factors,promote the expression of anti-inflammatory factors and other mechanisms to inhibit inflammation and thus suppress scar lesions.(2)miRNAs with high expression of exosomes derived from mesenchymal stem cells can reduce the secretion of matrix metalloproteinases,regulate the balance between matrix metalloproteinase inhibitors and matrix metalloproteinases,inhibit the proliferation and migration of fibroblasts and myofibroblasts,directly reduce the production of collagen and other mechanisms,and ultimately lead to the normal degradation of extracellular matrix,thereby inhibiting excessive tissue remodeling and cicatricial lesions.(3)miRNAs with high expression of exosomes from mesenchymal stem cells can improve the resistance of scar fibroblasts to oxidative stress by regulating reactive oxygen species and hypoxia-inducing factors,and then regulate the proliferation and apoptosis of scar fibroblasts to inhibit scar lesions.(4)Exosomes derived from mesenchymal stem cells have good prospects for scar treatment.Studies on this aspect can find mirnas that regulate inflammatory cells,inflammatory factors,signaling pathways,matrix metalloproteinases,fibroblasts,reactive oxygen species,hypoxia-inducing factors and other key factors from the three aspects of inflammation,tissue remodeling and oxidative stress.Then,by inducing mesenchymal stem cells with high expression of the above miRNA,exosomes were extracted,and finally verified and clinical trials were carried out.

The role of comprehensive intervention measures in improving the patho-gen detection rate of hospitalized patients before antimicrobial therapy / 中国感染控制杂志

Objective To understand the pathogen detection of hospitalized patients before antimicrobial therapy in a hospital through implementation of comprehensive intervention measures,and provide reference basis for the de-velopment of targeted measures.Methods Hospitalized patients who received therapeutic antimicrobial agents in this hospital were selected as the research subjects.Patients who were hospitalized from January to May 2022 were selected as the pre-intervention group,comprehensive intervention measures were taken from June to October 2022,and those who were hospitalized from November 2022 to March 2023 were selected as the post-intervention group.The pathogen detection rate before antimicrobial therapy,sterile specimen detection rate,antimicrobial use rate,de-tection rate of key multidrug-resistant organisms of patients before and after the intervention were analyzed.Results Compared to before intervention,the proportion of pathogen detection rate before antimicrobial therapy(62.09％vs 74.04％),detection rate of healthcare-associated infection diagnosis-related pathogens(62.82％vs 92.73％),and sterile specimen detection rate(35.17％vs 41.06％)of hospitalized patients after intervention all increased signifi-cantly,with statistically significant differences(all P＜0.05).After intervention,pathogen detection rate before the combination use of key antimicrobial agents was not statistically different from before intervention(93.33％vs 90.48％,P＞0.05),while antimicrobial use rate was lower than before intervention(39.93％vs 44.95％,P＜0.05).There was no statistically significant difference in the detection rate of key multidrug-resistant organisms be-fore and after intervention(all P＞0.05).Conclusion Adopting scientific and rational intervention measures can improve the pathogen detection rate,provide a reference basis for the rational use of antimicrobial agents.There was no significant improvement in the pathogen detection rate before the combination use of key antimicrobial agents and the detection rate of key multidrug-resistant organisms,indicating that relevant measures still need to be further optimized.

Career development of targeted admission medical students:A seven-year follow-up analysis based on four medical colleges / 中国卫生政策研究

Objective:Utilizing a seven-year panel data set of a targeted admission medical student cohort,this study aims to examine their career development and provide insights for retaining healthcare talent in township health centers and village clinics in the central and western rural areas of China.Method:Starting from 2015,cohorts of targeted and general clinical graduates from four medical colleges in central and western China were selected and tracked for their career progression.Results:The targeted graduates'standardized residency training and medical licensing examination pass rates were similar to those of general clinical graduates.They advanced more quickly in professional titles and positions,with 82.5%becoming attending physicians and 16.2%obtaining positions in the seventh year after graduation.However,their monthly income was significantly lower than that of general clinical graduates,and this income discrepancy expanded annually.As of December 2022,among the 493 targeted graduates who completed their contracts,38.5%stayed in grassroots positions.Of those who left,60%moved to county-level or higher public hospitals,7.9%pursued further studies,and 27.7%were unemployed.Conclusion:Targeted graduates are well-trained and advance rapidly in their careers,but their lower income significantly impacts their willingness to remain at the grassroots level.After completing their service period,about one-third of the targeted graduates choose to stay in grassroots positions.

miR-125a targeting transcription factor atonal homolog 8 is involved in the progression of lung adenocarcinoma / 中国医科大学学报

Objective To investigate the effect of transcription factor atonal homolog 8(ATOH8)and miR-125a on lung cancer progres-sion and its potential upstream regulatory mechanism.Methods ATOH8 expression levels in lung adenocarcinoma and their correlation with survival rate were analyzed using the online database UALCAN.miR-125a expression levels in lung adenocarcinoma and their rela-tionship with lung cancer progression were also analyzed using the UALCAN database.Total RNA extracted from lung adenocarcinoma tumors and adjacent normal tissues was used to perform real-time PCR in order to analyze these expression levels.The effect of ATOH8 overexpression on lung adenocarcinoma cell survival was detected using CCK-8 assays.A miR-125a mimic and inhibitor were transfected into lung adenocarcinoma cells,and ATOH8 expression levels were detected by real-time PCR and Western blotting.Results Statistical analysis showed that ATOH8 was significantly down-regulated in lung adenocarcinoma tissues(P＜0.01)and ATOH8 overexpression significantly reduced the survival of lung adenocarcinoma cells(P＜0.05).Furthermore,the five-year survival rate of patients with high ATOH8 expression levels was significantly increased(P＜0.05).miR-125a can bind to the 3'untranslated regions(3'UTR)of ATOH8 and significantly inhibit its expression levels(P＜0.05).However,miR-125a was significantly up-regulated in lung adenocarcinoma patients with a history of smoking,middle and advanced stage,and lymphatic metastasis(P＜0.05).Conclusion ATOH8,as a poten-tial tumor suppressor gene,can inhibit lung adenocarcinoma cell survival and affect the five-year survival rate of patients.miR-125a expression levels were closely related to smoking history,tumor stage,and lymphatic metastasis.Overall,the inhibiting effect of miR-125a against ATOH8 is a potential reason for abnormal ATOH8 expression in lung adenocarcinoma.

Establishment and of preliminary verification of automatic auditing rules for routine coagulation assays / 中国医学装备

Objective:To establish auto verification rules for the routine coagulation assays,and to provide reference for clinical laboratories to improve the quality and efficiency of results verification.Methods:A total of 24,510 specimens of sodium citrate anticoagulation routine coagulation test from the laboratory departments of eight hospitals including the First Medical Center,Chinese PLA General Hospital during January to March 2020 were collected and randomly divided into a rule establishment group and a rule verification group,with 6,670 specimens in the rule establishment group,including 2,056 Delta checks,and 17,840 specimens in the rule validation group,including 3,210 Delta checks.The activities of prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(Fib),thrombin time(TT),D-dimer(DD)and/or antithrombin(AT)were detected by Stago STA R Max automatic coagulation analyzer and supporting reagents.Taking the manual verification results as the standard,the auto verification and manual false negative rate(invalid verification),false positive rate(invalid interception),pass rate,positive coincidence rate,negative coincidence rate,verification consistency rate and specimen turnaround time(TAT)of the two groups were calculated.Results:The auto verification rules and the application process were preliminarily established,including internal quality control,alarm information,auto verification scope,critical value and deviation value inspection.In the rule establishment group,the single item pass rate was 82.6%-92.4%,and the overall pass rate was 73.8%.The consistency rate between auto verification and manual verification was 98.2%,and the positive coincidence rate and negative coincidence rate were 24.4%and 73.8%,respectively.In the rule verification group,the single item pass rate was 86.4%-91.5%,and the overall review pass rate was 71.5%.By simulating the application of auto verification rules,the average TAT of two hospitals among the eight hospitals was shortened by 1.5 hours and 2.1 hours,respectively.Conclusion:The application of auto verification rules can reduce workload of manual verification,and significantly shorten the TAT,and improve the report efficiency of the laboratory.

False-positive HIV-1 nucleic acid testing results in patients with severe thalassemia after receiving cell and gene therapy / 中华检验医学杂志

A 11-year old female patient with severe thalassemia, receipt a lentivirus-based cell and gene therapy (CGT) therapy in Shenzhen Children′s Hosptial on July 27th, 2021. At the two follow-up visits after discharge, patient were continuously tested positive for HIV screening through HIV Ag/Ab Combo assay (chemiluminescence Immunoassay), and the viral load results of HIV-1 nucleic acid testing (NAT) were both>5 000 copies/ml. The patient can be diagnosed with HIV infection according to the National Guideline for Detection of HIV/AIDS(2020 Revised Edition). The thorough investigation findings and supplementary experiment results indicated that the false-positive HIV-1 NAT results was caused by cross-reactivity between the target sites detected by conventional HIV-1 NAT reagents and the lentiviral vectors fragments integrated into the genome of patient′s hematopoietic stem/progenitor cells. In conclusion, it is important for laboratories to select appropriate HIV-1 NAT testing platforms which won′t cause cross-reactivity for the testing of samples from patients who have been treated with HIV-derived vectors. It is also recommended to design and develop NAT testing platforms with multiple target regions labeled by different fluorescents for HIV NAT supplementation experiment to reduce the risk of false-positive diagnoses of HIV infection.

Analysis of the current situation, advantages and difficulties of standardized management of Investigator Initiated Clinical Trials / 中华医学科研管理杂志

Objective:To assess the current situation, advantages, and difficulties of standardized management in Investigator-Initiated Clinical Trials (IIT).Methods:This article summarized the requirements and policies for clinical research management, the development of clinical research domestically and internationally, the achievements and advantages of clinical research management development in China, and the main problems and difficulties with the standardized IIT management in China, and compiled the experiences and models of several medical institutions in IIT management.Results:While China has a large number of clinical medical publications and is ranked high in the world, the quality of the publications needs to be further improved. Domestic management requirements for IIT were gradually improving, providing a basis for medical institutions to implement standardized management throughout the lifecycle of IIT, and achieve certain progress. However, there were still challenges in the departmental divisions, the unification of management standards, whole-process management and quality control, the scientific review, high-risk project management, and registration.Conclusions:Drawing on the excellent experience of domestic medical institutions, measures including identifying a primary responsible department, establishing unified supervision and inspection standards, and implementing a whole life cycle management may help overcome the challenges in IIT management and improve the quality and efficiency of IIT management.

JIA Yingjie's Experience in the Diagnosis and Treatment of Esophageal Cancer / 浙江中医药大学学报

[Objective]To summarize the clinical experience of Professor JIA Yingjie,a renowned traditional Chinese medicine practitioner in the treatment of esophageal cancer.[Methods]Through clinical following up,collect and analyze Professor JIA's understanding of the etiology and pathogenesis of esophageal cancer and related medication,and a case of was attached as evidence.[Results]Professor JIA believes that the pathogenesis of esophageal cancer can be summarized as"phlegm coagulation and Qi stagnation"in the early stage,"primitive deficiency"in the late stage as a whole,"phlegm and blood stasis intermingle,Qi and blood stasis obstruct the diaphragm"in local areas,phlegm,Qi,and blood stasis solidify and poison transform into cancer turbidity,and block and form tumors.Clinical differentiation and treatment should always focus on"Qi",with a particular emphasis on regulating the"Qi mechanism".The lungs,spleen and liver are in sync,and dynamic differentiation and treatment should be carried out based on the characteristics of the patient's tongue and pulse.Medication should emphasize the use of"strengthening the body resistance righting"and"dispelling pathogenic factors"to achieve the dissipation of blood stasis,the elimination of cancer toxins and the opening of the diaphragm.[Conclusion]Based on the characteristics of esophageal cancer and the patient's physical constitution,Professor JIA combines disease and syndrome differentiation in treating esophageal cancer,providing a certain reference value and new path for clinical medication.

Clinical features of severe acute respiratory syndrome coronavirus 2 Omicron variant infection in children: an analysis of 201 cases / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection.@*METHODS@#A retrospective analysis was performed on the medical data of 201 children with coronavirus disease 2019 (COVID-19) who were hospitalized and diagnosed with SARS-CoV-2 Omicron variant infection in Quanzhou First Hospital from March 14 to April 7, 2022. Among the 201 children, there were 34 children with asymptomatic infection and 167 with symptomatic infection. The two groups were compared in terms of clinical features, results of experimental examinations, and outcome.@*RESULTS@#Of all the 201 children, 161 (80.1%) had a history of exposure to COVID-19 patients and 132 (65.7%) had a history of COVID-19 vaccination. Among the 167 children with symptomatic infections, 151 had mild COVID-19 and 16 had common COVID-19, with no severe infection or death. Among the 101 children who underwent chest CT examination, 16 had ground glass changes and 20 had nodular or linear opacities. The mean time to nucleic acid clearance was (14±4) days for the 201 children with Omicron variant infection, and the symptomatic infection group had a significantly longer time than the asymptomatic infection group [(15±4) days vs (11±4) days, P<0.05]. The group vaccinated with one or two doses of COVID-19 vaccine had a significantly higher positive rate of IgG than the group without vaccination (P<0.05). The proportions of children with increased blood lymphocyte count in the symptomatic infection group was significantly lower than that in the asymptomatic infection group (P<0.05). Compared with the asymptomatic infection group, the symptomatic infection group had significantly higher proportions of children with increased interleukin-6, increased fibrinogen, and increased D-dimer (P<0.05).@*CONCLUSIONS@#Most of the children with Omicron variant infection have clinical symptoms, which are generally mild. The children with symptomatic infection are often accompanied by decreased or normal blood lymphocyte count and increased levels of interleukin-6, fibrinogen, and D-dimer, with a relatively long time to nucleic acid clearance. Some of them had ground glass changes on chest CT.

Clinical Value of Translocator Protein Gene in Evaluating the Efficacy of FLT3-ITD/DNMT3A R882 Double-Mutated Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML).@*METHODS@#Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation).@*RESULTS@#The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011).@*CONCLUSION@#TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.

Study on the neuroprotective mechanism of mesenchymal stem cells combined with low⁃intensity transcranial ultrasound therapy in TBI rats / 安徽医科大学学报

Objective@#To investigate the neuroprotective effect of mesenchymal stem cells (MSC) combined with low⁃intensity transcranial ultrasound (LITUS) treatment on traumatic brain injury (TBI) . @*Methods@#Seventy⁃two SD rats were randomly divided into four groups , namely , control group , TBI group , MSC injection group , and combined treatment group , with 18 rats in each group. TBI model was established by applying a pneumatic controlled cortical impingement instrument. Within 24 h after surgery , MSC was injected into the injury site by microinjector and microinjector pump using in situ injection. After injection , the injury site was treated with LITUS for 28 consecutive days using an ultrasound stimulator. The modified neurological functioning score ( mNSS) was performed on rats in each group at 1 , 3 , 7 , 14 , 21 and 28 days postoperatively , and then the brains were extracted to detect pathological changes at the injury site and the mRNA and protein expression of brain⁃derived neurotrophic factor (BDNF) , growth associated protein⁃43 ( GAP⁃43) , postsynaptic density protein⁃95 ( PSD⁃95 ) and glial fibrillary acidic protein(GFAP) by HE staining , immunohistochemistry , Western blot and RT⁃PCR.@*Results@#Compared with the control group , the mNSS score increased in the TBI group (P < 0. 05) , the expression of GAP⁃43 and PSD⁃95 decreased , and the expression of GFAP increased ( P < 0. 05 ) ; Compared with the TBI group , the mNSS score of MSC group was lower (P < 0. 05) , the expression of BDNF , GAP⁃43 , PSD⁃95 increased , and the expression of GFAP decreased (P < 0. 05) ; mNSS scores were lower in the combined treatment group than those in the MSC group (P < 0. 05) , the expression of BDNF , GAP⁃43 , PSD⁃95 increased , and the expression of GFAP decreased (P < 0. 05) .@*Conclusion@#The mechanism by which MSC combined with LITUS exerts neuroprotective effects in TBI may be related to the promotion of BDNF , GAP⁃43 , and PSD⁃95 expression and reduction of GFAP expression.

The role of cAMP /Epac / Rap1 signaling pathway regulate the secretion of IL-1 β, TNF-α, BDNF from NG2 cell and the effect of Jujuboside A / 安徽医科大学学报

Objective@#To investigate whether the cyclic adenosine monophosphate (cAMP) / exchange proteins directly activated by cAMP (Epac) / ras-related protein 1 ( Rap1 ) signalling pathway is involved in the intervening mechanisms of interleukin-1 β (IL-1 β) ，tumor necrosis factor-α (TNF-α) ，brain-derived neurotrophic factor (BDNF) and Jujuboside A(JuA) secretion by NG2 cells． @*Methods@#NG2 cells were cultured in vitro and the experiment was divided into control group ，pertussis toxin ( PTX) group ，ESI-09 group，JuA group and positive drug group．The effect of different concentrations of JuA on the survival rate of NG2 cells was detected by CCK-8 method，and the expression of IL-1 β , TNF-α , BDNF，cAMP，Epac，Rap1 mRNA and protein in each group was detected by RT-PCR and Western blot. @*Results@#Compared with the control group，the PTX group decreased the expression of IL-1 β and TNF-α mRNA and protein (P＜0. 01) and increased the expression of cAMP and BDNF mRNA and protein (P＜0. 01) ; the ESI-09 group increased the expression of IL-1 β and TNF-α mRNA and protein (P < 0. 05) and decreased the expression of BDNF，Epac and Rap1 mRNA and protein expression (P＜0. 01) ; the JuA group and positive drug group increased IL-1 β , TNF-α , BDNF，cAMP，Epac，Rap1 mRNA and protein expression (P＜0. 01) ．@*Conclusion @#The cAMP / Epac / Rap1 signaling pathway is involved in the secretion of IL-1 β , TNF- α , and BDNF by NG2 cells．JuA may act on cAMP / Epac / Rap1 signaling pathway to affect the secretion of BDNF by NG2 cells.