Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China / 中国当代儿科杂志

OBJECTIVES@#To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China.@*METHODS@#A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.@*RESULTS@#A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance.@*CONCLUSIONS@#This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition) / 中草药·英文版

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Effects of EW-7197 on the proliferation and migration of TGF-β1 induced human Tenon fibroblasts and its mechanism / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of ALK5 inhibitor EW-7197 on the proliferation and migration of human Tenon fibroblasts(HTFs)induced by transforming growth factor-β1(TGF-β1)and its mechanism.METHODS: The cell proliferation rate was detected by MTS assay, and the optimal concentration and time of EW-7197 were explored. Then HTFs were divided into three groups: normal control group, TGF-β1 induced group and TGF-β1+EW-7197 group. Cell migration was observed by Transwell assay. The protein expression levels of Fibronectin, α-SMA, as well as the phosphorylated Smad2, Smad3(p-Smad2, p-Smad3)were measured by Western blot.RESULTS: MTS assay showed that the proliferation rate of cells treated with 6.0 μmol/L EW-7197 for 24h was the lowest(all P<0.01). Transwell assay showed that the migrated number of HTFs in TGF-β1 induced group was 228.0±17.0/field, which was significantly more than that in normal control group(149.0±15.0/field)and TGF-β1+EW-7197 group(46.0±8.0/field; all P<0.01). Western blot showed that the protein relative expression levels of Fibronectin, α-SMA and p-Smad2, p-Smad3 of HTFs in TGF-β1 induced group were significantly higher than that in normal control group and TGF-β1+EW-7197 group(all P<0.001).CONCLUSION:EW-7197 can suppress the proliferation and migration of TGF-β1-induced HTFs through TGF-β/Smad signaling pathways.

Whole view of the immune microenvironment of biliary tract cancer / 中华外科杂志

Biliary tract cancer is a group of malignancies which originate from biliary epithelium, and adenocarcinoma is the main pathological type. Although surgical resection is the only radical treatment strategy, most biliary tract cancer patients are diagnosed at locally advanced stage or with distant metastasis. Biliary tract cancer is highly resistant to the conventional chemoradiotherapy and the emerging immunotherapy including immune checkpoint inhibitors, owing to the suppressive immune microenvironment. In a whole view, this paper discussed the anti-tumor and tumor-promoting immune responses of the various immune cells and stromal cells in the immune microenvironment of biliary tract cancer, as well as their correlation with prognosis. The understanding of the whole view of immune microenvironment in biliary tract cancer patients could further inform the design of clinical trials of immunotherapy or combination therapy.

A multi-center study on evaluation of leukocyte differential performance by an artificial intelligence-based Digital Cell Morphology Analyzer / 中华检验医学杂志

Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.

Current status of surgery for portal hypertension in China: a national multi-center survey analysis / 中华器官移植杂志

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Clinical value of ultrasound-guided fine-needle aspiration biopsy in the diagnosis of thyroid cancer and assessment of cervical lymph node metastasis / 中国基层医药

Objective:To explore the clinical value of ultrasound-guided fine-needle aspiration biopsy in the diagnosis of thyroid cancer and assessment of cervical lymph node metastasis.Methods:The clinical data of 90 patients with thyroid cancer who received treatment in Zhoushan Hospital from October 2018 to April 2021 were retrospectively analyzed. All patients underwent a two-dimensional ultrasound examination and ultrasound-guided fine-needle aspiration biopsy before surgery. Taking surgical and pathological diagnosis as the gold standard, the efficiency of two-dimensional ultrasound examination versus ultrasound-guided fine-needle aspiration biopsy in the diagnosis of thyroid cancer and cervical lymph node metastasis and in the identification of benign and maligant lymph nodes were investigated. Multivariate Logistic regression analysis was performed to analyze the correlation between different ultrasound signs and the detection rate of lymph nodes. Results:Pathological results showed that among the 90 patients, 73 patients had thyroid cancer, and 17 patients had benign lesions. Ultrasound-guided fine-needle aspiration biopsy results showed that 70 patients had thyroid cancer, and 20 patients had benign lesions, including 4 cases of missed diagnosis and 2 cases of misdiagnosis. The diagnostic sensitivity, specificity, accuracy rate, and Kappa value were 94.52%, 88.24%, 93.33%, and 0.79, respectively. These were highly consistent with the surgical and pathological diagnosis (Kappa value > 0.75). Two-dimensional ultrasound revealed 69 patients with thyroid cancer and 21 patients with benign lesions, including 7 cases of missed diagnosis and 4 cases of misdiagnosis. The diagnostic sensitivity, specificity, accuracy rate, and Kappa value were 90.41%, 76.47%, 87.78%, and 0.63, respectively. Pathological results revealed that cervical lymph node metastasis occurred in 12 patients, and it did not occur in 78 patients. The diagnostic sensitivity, specificity, accuracy rate, and Kappa value of ultrasound-guided fine-needle aspiration biopsy were 83.33%, 97.50%, 95.65%, and 0.81 respectively. These were highly consistent with surgical and pathological results (Kappa value > 0.75). The diagnostic sensitivity, specificity, accuracy rate, and Kappa value of two-dimensional ultrasound examination were 75.00%, 94.87%, 92.22%, and 0.67, respectively. A total of 156 lymph nodes were detected by ultrasound-guided fine-needle aspiration biopsy, including 103 benign lymph nodes and 53 malignant lymph nodes, with a diagnostic accuracy rate of 94.17% and 96.22%, respectively. A total of 173 lymph nodes were detected by two-dimensional ultrasound, including 111 benign lymph nodes and 62 malignant lymph nodes, with a diagnostic accuracy rate of 91.89% and 91.93%, respectively. There were no significant differences in the diagnostic accuracy of benign and malignant lymph nodes between the two examination methods ( χ2 = 0.42, 0.92, both P > 0.05). Multivariate logistic regression analysis showed that hyperechoic masses, cystic lesions, and internal calcification were significantly correlated with the detection rate of lymph nodes diagnosed by two-dimensional ultrasound and ultrasound-guided fine-needle aspiration biopsy ( OR = 6.64, 5.32, 4.12, 7.07, 5.60, 5.06, all P < 0.05). Conclusion:Ultrasound-guided fine-needle aspiration biopsy has high diagnostic efficiency for thyroid cancer and cervical lymph node metastasis. Ultrasound signs of hyperechoic mass, cystic lesions, and internal calcification are significantly correlated with the detection rate of lymph nodes.

Antagonistic effect of SC79 on high glucose-induced apoptosis of RPE cells and its regulatory mechanism on AKT-XIAP signaling pathway / 中华实验眼科杂志

Objective:To investigate the antagonistic effect and potential mechanism of specific AKT activator SC79 on the apoptosis of human retinal pigment epithelial (ARPE)-19 cells induced by high glucose in vitro. Methods:The ARPE-19 cells were cultured in high glucose medium (containing 30 mmol/L glucose) plus 5, 10 or 20 μg/ml SC79, respectively.After 6-, 12- and 24-hour culture, the optimal experimental concentration and timing were determined according to cell proliferation rate.Then ARPE-19 cells were divided into four groups, normal control group cultured in normal medium containing 5.6 mmol/L glucose for 48 hours, mannitol group cultured in medium containing 5.6 mmol/L glucose and 24.4 mmol/L mannitol for 48 hours, high glucose group cultured in high glucose medium for 48 hours, and high glucose+ SC79 group cultured in normal medium containing 10 μg/ml SC79 for 12 hours plus in high glucose medium for 36 hours.The proliferation rate of APRE-19 cells was detected by MTS assay.The apoptosis rate was measured by flow cytometry.The relative expression levels of phosphorylated protein kinase B (p-Akt), X-linked inhibitor of apoptosis protein (XIAP), caspase-9, caspase-3 and its active fragments (active-caspase-3) were assayed by Western blot.The ARPE-19 cells were divided into Neg-shRNA group, AKT shRNA group and blank control group and were treated with the corresponding transfection complex and serum-free medium.The AKT mRNA expression was detected by real-time PCR.The transfected ARPE-19 cells were divided into Neg-shRNA+ SC79 group and AKT shRNA+ SC79 group and were cultured according to the culturing method of high-glucose+ SC79 group.The apoptosis rate of the two groups was tested by flow cytometry.Results:Among different concentrations of SC79 and treatment times, the proliferation rate of cells treated with 10 μg/ml SC79 for 12 hours was the highest.The proliferation rate of ARPE-19 cells in high-glucose group was significantly lower than that in normal control group, mannitol group and high-glucose+ SC79 group, and the differences were statistically significant (all at P<0.01). The apoptosis rate of cells in the high-glucose group was (52.27±3.21)%, which was significantly higher than (3.90±0.71)% in normal control group and (20.70±3.62)% in high-glucose+ SC79 group (both at P<0.01). The relative expression levels of p-Akt, XIAP, caspase-9 and caspase-3 were significantly lower and the relative expression level of active-caspase-3 was significantly higher in high glucose group than those in normal control group and high-glucose+ SC79 group (all at P<0.05). The relative expression level of AKT mRNA in normal control group, Neg-shRNA group and AKT shRNA group was 0.60±0.07, 0.59±0.03 and 0.11±0.10, respectively, showing a statistically significant difference among the groups ( F=30.44, P<0.01). The apoptosis rate of cells in the AKT shRNA+ SC79 group was significantly higher than that in high-glucose+ SC79 group and Neg-shRNA+ SC79 group (both at P<0.001). Conclusions:SC79 can partially antagonize the apoptosis of ARPE-19 cells induced by high glucose, which is related to the activation of AKT/XIAP pathway and the inhibition of the caspase family.

Analysis on the Current Situation and Influencing Factors of Ethical KAP among Clinical Researchers / 中国医学伦理学

【Objective:】 To understand the current situation and influencing factors of ethical knowledge, attitude, and practice (KAP) among clinical researchers, enhance their ethical awareness, and improve the quality of clinical researches. 【Methods:】 A self-designed questionnaire was used to conduct a convenient sampling survey of medical staff who have participated in clinical study. 【Results:】 A total of 6,021 subjects were investigated, with males accounting for 28.46% and females accounting for 71.53%. The average age of them was (37.47±11.46) years old. The total score of ethics and the mean scores of the three dimensions of knowledge, attitude and practice were (70.62±12.99), (59.63±12.50), (79.55±19.62) and (74.92±18.29), respectively. Multiple linear regression analysis showed that researchers with male, tertiary hospitals, doctors, ethics-related part-time jobs, postgraduate education, associate senior title or above, and training experience scored higher (P<0.05). 【Conclusion:】 Ethical attitudes have a significant mediating effect between knowledge and practice, accounting for 62.72% of the total effect. Researchers recognize the importance of ethics, but it is urgent to strengthen their knowledge learning and practical application.

Determination of 10 organophosphorus flame retardants in drinking water by On-line SPE-UPLC-MS/MS / 公共卫生与预防医学

Objective To establish a method for the determination of 10 organophosphorus flame retardants in drinking water by on-line solid phase extraction coupled with high performance liquid chromatography-tandem mass spectrometry (On-line SPE-UPLC-MS/MS). Methods After adding the internal standard, the water sample was filtered by Millipore filtration, and then concentrated and detected by Online SPE-UPLC-MS/MS. Samples were concentrated by C8 SPE column and separated by C18 column with acetonitrile-water-formic acid as the mobile phases gradient elution，and were detected by multiple reaction monitoring (MRM) acquisition under anion mode. Results The 10 organophosphorus flame retardants all displayed good linear relationships within a certain range of concentrations, with the correlation coefficients being more than 0.990. The method detection limits were 0.60-5.50 ng/L, and the spiked recoveries of low, medium and high concentrations were 64%-106% , 83%-104% and 85%-99%, respectively. Conclusion The method is simple, sensitive, rapid, accurate and reliable, so it is applicable for the determination of 10 organophosphorus flame retardants in drinking water.

Incidence trend of clinical characteristics and outcome of lung cancer in Ma'anshan District / 公共卫生与预防医学

Objective To investigate the incidence trend, clinical characteristics and prognosis of lung cancer in Ma'anshan area. Methods The data of 398 lung cancer patients admitted to the Department of Respiratory and Critical Care Medicine, Maanshan People's Hospital in Ma'anshan area from January 2018 to May 2022 were selected, and the composition ratio of age, sex, histology and outcome data and its change trend over time were analyzed. Results The minimum age of lung cancer patients in this area was 35 years old, the maximum age was 92 years old, and the average age was (69.94 ± 9.76) years old . The patients were mainly from 70 to 79 years old, followed by 60 to 69 years old and >80 years old . The number of patients was decreasing year by year . The patients with squamous cell carcinoma transferred from 60 to 69 years old to 70 to 79 years old, and adenocarcinoma mainly concentrated in 70 to 79 years old . The incidence of squamous cell carcinoma increased (P=0.006), while that of adenosquamous carcinoma decreased (P=0.005) . The improved discharge rate of lung cancer was increasing year by year (P<0.001) , and the cured discharge rate (P=0.044) was decreasing year by year. The improved discharge rate of men was increasing year by year (P=0.039) , while the improved discharge rate of women was decreasing and then increasing, and the improved discharge rate in 2020 was the lowest (P=0.027) . The mortality increased with age (P=0.002). Conclusion From 2018 to 2022, the number of patients in Ma'anshan area will decrease year by year . The patients were mainly in the 70-79 age group . The incidence rate of adenocarcinoma was the highest , while the incidence rate and age of squamous cell carcinoma were on the rise . The overall improvement discharge rate is increasing year by year , and the cure discharge rate is decreasing year by year. The improvement discharge rate for men is increasing year by year , and vice versa for women.

Suicide attitude and related factors of college students with mental disorders in Shaoxing City / 中国学校卫生

Objective@#To analyze the suicide attitude and influencing factors of college students with mental disorders in Shaoxing City, and to provide a basis for improving the attitude of college students with mentaldisorders towards suicide. @*Methods@#From January 2018 to December 2021, 1 100 college students, among which 110 were previously confirmed by medical institutions to have mental disorders, were selected from two schools in Shaoxing, including Shaoxing University and Yuexiu Foreign Languages College, to participate in a questionnaire survey. Univariate and multivariate Logistic regression analysis were used to identify the main factors affecting the suicide attitude of college students with mental disorders.@*Results@#Univariate analysis showed that the influence of different nature of college students with mental disorders on suicide attitude was related to age, gender, origin, suicide ideation, whether suicidal thoughts can be controlled, impulsive personality type, problem solving style, the differences were statistically significant ( χ 2/t=9.01, 15.05, 5.90, 5.86, 6.47, 4.92, 13.48, P <0.05). Multivariate Logistic regression analysis showed that age, gender, origin, suicidal ideation, uncontrolled suicidal thoughts, impulsive personality type, problem solving style were the main factors influencing the suicidal attitude of college students with mental disorders ( OR=3.13, 3.06, 2.89, 3.22, 3.25, 3.13 , 3.16, P <0.05).@*Conclusion@#problem solving and other factors. The selection of targeted treatment plan can improve the mental disorder condition of college students and promote the recovery of the disease.

Study on the correlation between opioid-induced constipation and gene polymorphism / 中国药房

OBJECTIVE To investigate the effect of gene polymorphism on opioid-induced constipation. METHODS The target genes related to opioid-induced constipation were screened out through searching guidelines， databases and evidence-based medical data， and then 100 cancer pain patients who received opioid drugs for analgesia were included as the study subjects. According to whether there were adverse effects of constipation after medication or not， they were divided into test group and control group， with 50 cases in each group. The target gene was detected by PCR or fluorescence in situ hybridization. The SNPStats program was used to carry out Hardy-Weinberg balance test and correlation analysis between gene polymorphism and opioid-induced constipation. The multivariate Logistic regression analysis was used to explore the relevant predictive factors of opioid-induced constipation， and receiver operating characteristic （ROC） curve of subjects was drawn to analyze the effectiveness of each predictive factor in predicting opioid-induced constipation. RESULTS CYP2D6， CYP3A5*3， ABCB1 and OPRM1 were selected as target genes for detection. The results of genotype detection showed that the frequency distribution of CYP2D6 （rs1065852， rs1135822， rs16947， rs28371725， rs28371735）， CYP3A5*3 （058rs776746）， ABCB1 （062rs1045642）， OPRM1 （047rs1799971） alleles were consistent with Hardy-Weinbergbalance test. The correlation analysis results showed that the proportion of genotype GG and AG in CYP3A5*3 （058rs776746， 163.com A＞G） and genotype AA and AG in OPRM1 （047rs1799971， A＞G） of patients was significantly higher in test group than that in the control group （P＜0.05）. Multivariate Logistic regression analysis showed that medication duration， CYP3A5*3 and OPRM1 gene polymorphism could be used as predictors of opioid- induced constipation in patients （P＜0.05）. The ROC curve analysis results showed that the areas under the ROC curves for medication duration and CYP3A5*3， OPRM1 gene polymorphism were 0.648， 0.640 and 0.670， respectively， with the optimal cutoff values of 124.0， 0.5 and 0.5， respectively. CONCLUSIONS Genotype GG and AG in CYP3A5*3 （058rs776746，A＞G） and genotype AA and AG in OPRM1 （047rs1799971，A＞G） are associated with opioid-induced constipation， which are expected to become clinical predictors of opioid-induced constipation， and more attention should be paid to the occurrence of constipation in patients who have been taking opioids for a long time.

Medicated Serum of Bupleuri Radix Regulates HFL1 Apoptosis and Fibroblast-myofibroblast Transition via Smad3/Rheb Axis / 中国实验方剂学杂志

ObjectiveTransforming growth factor-β1 （TGF-β1） was used to stimulate human fetal lung fibroblast 1 （HFL1） for simulating the pathological process of idiopathic pulmonary fibrosis （IPF） and thereby the effects and mechanism of medicated serum of Bupleuri Radix against IPF were investigated. MethodTGF-β1 （10 μg·L-1） was employed to stimulate HFL1， and cells were treated with medicated serum of Bupleuri Radix （5%， 10%， 15%， 20%） for 24 h. Then cell proliferation rate was determined with cell counting kit-8 （CCK-8）. Subsequently， cells were classified into the control group （20% blank serum）， TGF-β1 group （20% blank serum and 10 μg·L-1 TGF-β1）， TGF-β1 + medicated serum of Bupleuri Radix group （5% blank serum， 15% medicated serum， and 10 μg·L-1 TGF-β1）， and TGF-β1 + SIS3 group （3 μmol·L-1 SIS3， 20% blank serum， 10 μg·L-1 TGF-β1）. Based on in situ end labeling （TUNEL） staining， the apoptosis rate was examined， and mRNA expression of apoptosis-related proteins B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax） and myofibroblast marker α-smooth muscle actin （α-SMA） was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression of α-SMA， Ras homolog enriched in brain （Rheb）， and phosphorylated （p）-Smad3 was determined by immunofluorescence. Expression of Rheb， p-Smad3， and Smad3 was examined by Western blot. ResultThe cell proliferation rate of TGF-β1 group increased compared with that of the control group （P<0.05）. The cell proliferation rate of TGF+15% medicated serum of Bupleuri Radix group and TGF+20% medicated serum of Bupleuri Radix group decreased compared with that of the TGF-β1 group （P<0.01）. Compared with the control group， TGF-β1 group showed decrease in apoptosis rate， increase in mRNA expression of Bcl-2 and α-SMA， reduction in Bax mRNA expression， and rise of α-SMA and Rheb protein expression and p-Smad3 level （P<0.05）. Compared with TGF-β1 group， TGF-β1 + medicated serum of Bupleuri Radix group and TGF-β1 + SIS3 group demonstrated high apoptosis rate， low Bcl-2 and α-SMA mRNA expression， high Bax mRNA expression， and low α-SMA and Rheb protein expression and p-Smad3 level （P<0.05）. ConclusionMedicated serum of Bupleuri Radix can inhibit TGF-β1-induced HFL1 proliferation and fibroblast-myofibroblast transition and promote fibroblast apoptosis by regulating the Smad3/Rheb axis.

Clinical features and genetic analysis of a child with acute form of Tyrosinemia type I due to a novel variant of FAH gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic basis for a child with acute form of tyrosinemia type I (TYRSN1).@*METHODS@#A child with TYRSN1 who presented at the Gansu Provincial Maternal and Child Health Care Hospital in October 2020 was selected as the subject. The child was subjected to tandem mass spectrometry (MS-MS) and urine gas chromatography-mass spectrometry (GC-MS) for the detection of inherited metabolic disorders, in addition with whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing.@*RESULTS@#The child's clinical features included abdominal distension, hepatomegaly, anemia and tendency of bleeding. By mass spectrometry analysis, her serum and urine tyrosine and succinylacetone levels have both exceeded the normal ranges. WES and Sanger sequencing revealed that she has harbored c.1062+5G>A and c.943T>C (p.Cys315Arg) compound heterozygous variants of the FAH gene, which were inherited from her father and mother, respectively. Among these, the c.943T>C was unreported previously.@*CONCLUSION@#Considering her clinical phenotype and result of genetic testing, the child was diagnosed with TYRSN1 (acute type). The compound heterozygous variants of the FAH gene probably underlay the disease in this child. Above finding has further expanded the spectrum of FAH gene variants, and provided a basis for accurate treatment, genetic counseling and prenatal diagnosis for her family.

Analysis of genotypes and phenotypes of three children with Cornelia de Lange syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and results of genetic testing in three children with Cornelia de Lange syndrome (CdLS).@*METHODS@#Clinical data of the children and their parents were collected. Peripheral blood samples of the pedigrees were collected for next generation sequencing analysis.@*RESULTS@#The main clinical manifestations of the three children have included growth delay, mental retardation, peculiar facies and other accompanying symptoms. Based on the criteria proposed by the International Diagnostic Consensus, all three children were suspected for CdLS. As revealed by whole exome sequencing, child 1 has harbored NIPBL gene c.5567_5569delGAA insTAT missense variant, child 2 has harbored SMC1A gene c.607A>G missense variant, and child 3 has harbored HDAC8 gene c.628+1G>A splicing variant. All of the variants were de novo in origin.@*CONCLUSION@#All of the children were diagnosed with CdLS due to pathogenic variants of the associated genes, among which the variants of NIPBL and HDAC8 genes were unreported previously. Above finding has enriched the spectrum of pathogenic variants underlying CdLS.

Clinical comprehensive evaluation for Chinese patent medicine based on evidence-based medicine and pharma- coeconomic model / 中国药房

OBJECTIVE To conduct a c omprehensive clinical evaluation method of Chinese patent medicine ，and to provide reference for rational clinical drug use. METHODS Taking the top 10 Chinese patent medicine injections for promoting blood circulation and removing stasis in Shandong province from 2016 to 2020 collected by the National Rational Drug Use Monitoring Network as an example ，the method combining health technology assessment with objective judgement analysis is used to construct the comprehensive evaluation index system ；based on evidence-based medical evidence and pharmacoeconomic model ，the safety ， effectiveness and economy of the drug were evaluated comprehensively ，and the scores were quantified. RESULTS & CONCLUSIONS The final scores of the 10 kinds of Chinese patent medicine injections were between 26 and 37 scores. Safflower yellow for injection scored the highest score in the treatment of cerebral infarction and angina pectoris of coronary heart disease ， while Ginkgo diterpene lactone meglumine injection and Shuxuening injection had the highest scores in the treatment of coronary heart disease. The clinical comprehensive evaluation method of Chinese patent medicine based on evidence-based medical evidence and pharmacoeconomic model can clarify the comprehensive value of Chinese patent medicine in clinic ，promote rational drug use in clinic ，and provide basis for the next adjustment of medical insurance catalogue and essential medicine catalogue ，decision-making of centralized procurement of related drugs.

Determination of eight volatile halogenated hydrocarbons in drinking water by headspace thermal desorption⁃gas mass spectrometry / 上海预防医学

ObjectiveTo establish a method for the determination of 8 volatile halogenated hydrocarbons in drinking water， including vinyl chloride， trichloroethylene， tetrachloroethylene， tetrachloromethane， chloroform， dichlorobromomethane， dichlorodibromomethane， and tribromomethane by headspace thermal desorption-gas mass spectrometry. MethodsThe water sample was kept in the headspace bottle at 60 ℃ for 40 min， and the volatile matter was transferred to the cold trap，subjected to thermal desorption， then analyzed by gas chromatography-mass spectrometry. ResultsThe linear ranges were 0.2‒20.0 μg·L-1 for vinyl chloride， 0.1‒20.0 μg·L-1 for chloroform， 0.02‒20.00 μg·L-1 for tetrachloromethane， 0.2‒20.0 μg·L-1 for trichloroethylene， 0.3‒20.0 μg·L-1 for dichlorobromomethane， 0.1‒20.0 μg·L-1 for tetrachloroethylene， 0.4‒20.0 μg·L-1 for dichlorodibromomethane， and 1.0‒20.0 μg·L-1 for tribromomethane. All the correlation coefficients were more than 0.997. The respective quantitative limits were 0.162， 0.073， 0.016， 0.184， 0.270， 0.071， 0.356 and 0.813 μg·L-1， and the respective recoveries were 98.0%‒101.0%， 102.0%‒110.0%， 99.2%‒101.0%， 95.5%‒96.2%， 96.0%‒102.0%， 100.0%‒102.0%， 99.0%‒105.0%， and 94.0%‒103.0%. ConclusionThe method is simple， sensitive， rapid， accurate and reliable， so it is applicable for the determination of 8 kinds of volatile halogenated hydrocarbons in drinking water.

Melatonin alleviates hypoxia-induced injury of PC12 cells by inhibiting SOX2 expression / 国际生物医学工程杂志

Objective:To investigate the effect of melatonin (MT) on hypoxia-induced injury of PC12 cells and its mechanism.Methods:PC12 cells cultured in vitro were divided into the control, the hypoxic, and three groups of hypoxic cells combined with different doses (low, medium, and high) of MT at 12.5, 25, and 50 μmol/L, respectively. Cell viability was measured by MTT. The expression of cysteine-containing aspartate 3 (cleaved caspase-3) and SOX2 proteins was detected by Western blot. The expression of SOX2 mRNA was detected by real-time fluorescence quantitative polymerase chain reaction (PCR). The activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) were detected by the kit. The combined treatment group with the most significant effect was selected as the hypoxia+MT group, and then the effects of hypoxia+MT, hypoxia+siRNA-NC, hypoxia+siRNA-SOX2, hypoxia+MT+pcDNA, and hypoxia+MT+pcDNA-SOX2 on cell viability, apoptosis, protein expression level of cleaved-caspase-3, protein and mRNA levels of SOX2, SOD activity, and MDA levels, respectively, were investigated.Results:Compared with the control group, cell survival rate and SOD activity in the hypoxia group were significantly decreased, while cell apoptosis rate, cleaved caspase-3 protein expression level, MDA content, SOX2 mRNA, and protein expression level were significantly increased (all P<0.05). The effects of low, medium, and high levels of MT and the low expression of SOX2 could ameliorate the above changes induced by hypoxia (all P<0.05), while the overexpression of SOX2 could alleviate the effects of MT on the viability, apoptosis, and oxidative stress of hypoxia-induced PC12 cells (all P<0.05). Conclusions:MT can reduce hypoxia-induced injury to PC12 cells by inhibiting the expression of SOX2.

Comparison of the thickness of macular ganglion cell inner plexiform layer in patients with a history of laser photocoagulation versus intravitreal injection of ranibizumab for retinopathy of prematurity / 中华眼底病杂志

Objective:To compare the thickness of the macular ganglion cell inner plexiform layer (mGCIPL) in patients with a history of laser photocoagulation (LP) versus intravitreal injection of ranibizumab (IVR) for retinopathy of prematurity (ROP).Methods:A retrospective clinical study. From June 2020 to January 2021, 70 eyes of 35 children with a history of surgery for ROP in Shenzhen Eye Hospital were included in the study. Among them, 18 males had 36 eyes, and 17 females had 34 eyes. The average age was 5.54±1.04 years. There were 18 patients (36 eyes) in LP group and 17 patients (34 eyes) in IVR group. There was no significant difference in age ( t=-1.956), sexual composition ratio ( χ2=0.030), birth gestational age ( t=-1.316) and birth weight ( t=-1.060) between the two groups ( P=0.059, 0.862, 0.197, 0.297). All the eyes underwent the examination of optical coherence tomography (OCT). An elliptical region of 14.13 mm 2 centered on macular fovea was scanned according to the macular cube 512×128 model of the Cirrus HD-OCT 5000. The software was used to automatically divide macular fovea into six sectors (superior, inferior, temporal-superior, temporal-inferior, nasal-superior and nasal-inferior) and the average and minimum thickness of mGCIPL. t test was used to compared mGCIPL thickness between two groups using independent samples. Pearson correlation analysis was used to evaluate the correlation between mGCIPL thickness and age, birth gestational age, birth weight. Results:Patients in IVR group had significantly decreased mGCIPL thickness than that in LP group in the six sectors (superior, inferior, temporal-superior, temporal-inferior, nasal-superior and nasal-inferior) and the average and minimum ( t=6.484, 6.719, 7.682, 7.697, 5.151, 5.008, 7.148, 6.581; P<0.05). The thickness of mGCIPL was not significantly correlated with age, birth gestational age, birth weight ( P>0.05). Conclusion:The thickness of mGCIPL in patients with IVR treatment history is thinner than that in LP treatment.