Construction of Evidence Body for Revision of Safety Information on Package Inserts of Chinese Patent Medicines in Post-marketing： Taking Xiaoke'an Capsules as an Example / 中国实验方剂学杂志

ObjectiveTo construct the evidence body for revision of safety information on package inserts of Chinese patent medicines in post-marketing by taking Xiaoke'an capsules as an example， so as to provide reference for the revision of instructions of Chinese patent medicines in post-marketing. MethodThe construction of the evidence body was guided by the theory of traditional Chinese medicine（TCM） and the Technical Guiding Principles for Revision of Safety Information Items in Instructions for TCMs After Marketing， and 8 categories and 25 specific items were taken as the main body of the evidence body， and information inclusion， integration， screening and improvement were carried out， then expert demonstrations were conducted， and finally modifications were made based on the opinions of the Center for Drug Evaluation to complete the revision of the safety information in the instructions of Xiaoke'an capsules. Result［Adverse reactions］ of Xiaoke'an capsules was revised to "monitoring data show that the following adverse reactions can be seen with this product：individual hypoglycemic reaction reports". ［Contraindications］ was revised to "contraindicated for those allergic to this product and its ingredients". ［Precautions］ was revised to "（1）pregnant women should use with caution， （2）elderly people should consult a physician， （3）people with spleen deficiency and dampness， spleen and stomach deficiency and cold， or those who eat less and have diarrhea should use with caution， （4）this product contains ginseng， should not be taken at the same time with TCM prescriptions or patent medicines containing veratrum and Wulingzhi， （5）pay attention to monitoring blood sugar during medication， （6）if any other discomfort occurs during medication， you should seek medical attention in time". The warning was revised to "use with caution by pregnant women， and pay attention to regular monitoring of blood sugar". ConclusionIn accordance with the content and process of the evidence body for the revision of safety information in the instructions， the revision of the safety information in the instructions of Xiaoke'an capsules has been completed， providing a strong basis for the rational and safe use of medication in the clinic.

Adrenal cortical carcinoma in children: a clinicopathological analysis of 25 cases / 中华病理学杂志

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of adrenal cortical carcinoma (ACC) in children. Methods: Twenty-five children with ACC diagnosed in the Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from March 2014 to August 2022 were retrospectively analyzed. The related literature was reviewed. Results: A total of 25 children with ACC were collected, including 11 males and 14 females, with a male to female ratio of 1.0∶1.3. The patient ages ranged from 8 months to 14 years (median, 4 years). Eighteen cases with clinical data had functional tumors (18/22, 81.8%) presenting with virilization or precocious puberty (15/18), symptoms related to hypercortisolism (8/18) or endocrine symptoms mixed with both (5/18), while 3 cases (3/22, 13.6%) had unknown clinical data. The clinical manifestations of four patients with nonfunctional tumors were an abdominal mass and/or abdominal pain, walking instability and others. Grossly, the average maximum diameter of the tumor was 9.4 cm. Most of the tumors were nodular and partially encapsuled. The cut surfaces were gray or gray brown, soft with hemorrhage. Histologically, the tumor cells were diffusely distributed, separated by a vascular-rich network. The tumor cells were large, with distinct nucleoli, abundant eosinophilic or clear cytoplasm, and round or oval nuclei. The mitotic index was high, and atypical mitoses were common. Necrosis, calcification, capsule invasion or/and venous invasion were present. In some cases, the tumor invaded the surrounding soft tissues or kidneys. Immunohistochemically, the tumor cells were diffusely positive for syn and SF1 and focally positive for α-inhibin, Melan A and Calretinin, but negative for CgA. Ki-67 proliferation index ranged from 2%-90%. TP53 gene status was examined in 7 cases, in which mutations were detected in 4 cases. Follow-up data was obtained in 21 patients, among whom 18 received chemotherapy and 3 received radiotherapy. Distant metastasis occurred in 13 patients. Median progression-free survival (PFS) was 11.2 months and median overall survival (OS) was 54.7 months. Patients aged less than 5 years had a better prognosis for OS (P<0.05) than the older ones (≥5 years), but a similar PFS (P>0.05). Male patients and Ki-67 proliferation index <15% had a better prognosis tendency for OS, but there was no statistically significant difference (P>0.05). Conclusions: ACC in children is a rare, often functional tumor associated with Li-Fraumeni genetic syndrome and has a poor prognosis. Diagnosis and differential diagnosis require a combination of morphological, phenotypic and clinical analysis.

A long-term evaluation of periodontal phenotypes before and after the periodontal-orthodontic-orthognathic combined treatment of lower anterior teeth in patients with skeletal Angle class Ⅲ malocclusion / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the changes of periodontal phenotype (width of keratinized gingiva, thickness and height of alveolar bone) of lower anterior teeth in patients with skeletal class Ⅲ malocclusion before and after the periodontal-orthodontic-orthognathic combined treatment.@*METHODS@#In the study, 20 patients with skeletal class Ⅲ malocclusion (6 males and 14 females) completed the periodontal-orthodontic-orthognathic combined treatment were included from March 2017 to June 2022, with 39 central incisors, 40 lateral incisors and 40 canines. The mean age was (25.40±4.27) years (20-34 years). The mean follow-up time was (3.70±1.05) years from the beginning of periodontal corticotomy regenerative surgery (PCRS) to the end of the combined treatment. Cone-beam computed tomography (CBCT) was used to measure the thickness, area and height of alveolar bone by the same researcher, taken before the PCRS (T0), 6 months after the PCRS (T1), 12 months after the PCRS (T2), before the orthognathic surgery (T3), and after the periodontal-orthodontic-orthognathic combined treatment (T4). The periodontal clinical parameters were used to evaluate changes in the soft tissue by another researcher, measured before the PCRS (T0) and after the combined treatment (T4). Changes of soft and hard tissue were evaluated by the periodontal phenotype.@*RESULTS@#The width of keratinized gingiva increased significantly (all P < 0.001) in lower anterior teeth, the central incisors, lateral incisors and canines increased by (1.82±1.57) mm, (2.03±1.48) mm and (2.05±1.27) mm, respectively. The proportion of thick periodontal biotype in the central and lateral incisors increased significantly (all P < 0.001), while the changes of periodontal biotypes in the lower canines were not obvious. The thickness of labial alveolar bone of lower anterior teeth all increased significantly after periodontal corticotomy regenerative surgery and the combined treatment (all P < 0.001). The area of labial alveolar bone of lower anterior teeth also increased significantly after the combined treatment (all P < 0.001). The whole area of labial and lingual alveolar bone of central and lateral incisors increased (P < 0.001), while the whole area of canines remained the same. All The height of the alveolar bone increased (all P < 0.001) on the labial side after the treatment.@*CONCLUSION@#The periodontal phenotypes of lower anterior teeth were significantly improved after the periodontal-orthodontic-orthognathic combined treatment in patients with skeletal Angle class Ⅲ malocclusion. The improvement was long-termly stable, and the periodontal risk was reduced.

Establishment and Clinical Application of Flow Cytometric Immunobead Array in Detecting Plasma von Willebrand Factor Antigen / 中国实验血液学杂志

OBJECTIVE@#To establish a novel flow cytometric immunobead array (FCIA) for detecting plasma von Willebrand factor antigen (vWF:Ag), and to analyze the clinical value of FCIA in predicting the prognosis of patients with ischemic stroke (IS).@*METHODS@#Anti-human vWF monoclonal antibody SZ29 IgG was coated on microspheres overnight, the diluted plasma was added after blocking, then incubated with FITC-conjugated sheep-anti-human vWF IgG polyclonal antibody, and finally detected by flow cytometry. The plasma vWF in 21 case of von Willebrand disease (vWD) and 105 controls (CTL) were detected by FCIA and ELISA, so as to carry out methodological assessment. Plasma vWF:Ag of 61 IS patients was detected by FCIA and the data of prognosis followed-up for 2-year were collected.@*RESULTS@#The linear fitting of FCIA was good (R2=0.99) without significant difference between FCIA and ELISA. The Bland-Altman bias was 1.12% with 95% limits of agreement that spanned from -45.06% to 47.30%, and the slope of the linear regression was 0.97 (r=0.86, P＜0.01). Importantly, the FCIA method was faster than ELISA, and superior to the ELISA in the detection of low levels of vWF:Ag. The levels of vWF:Ag, vWF:GPIbR and vWF:CB in IS patients were significantly higher than those in healthy controls (Z=8.36, 8.71, 6.22, respectively, P＜0.01).@*CONCLUSION@#The FCIA for detecting plasma vWF:Ag is not only an effective supplement to ELISA, but also the efficiency is faster and more sensitive, thus improves the diagnosis of type 3 vWD. Elevated levels of vWF: Ag in IS patients indicate the poor recovery of daily activities and prognosis.

Clinical Significance of FGFR1 Gene Abnormalities in Blood Tumors / 中国实验血液学杂志

OBJECTIVE@#To study the potential significance and clinical application of FGFR1 gene abnormality in the diagnosis, clinical features, pathological mechanism and treatment in hematological tumors.@*METHODS@#Clinical data of total of 29 patient with chromosome of 8 short arm (8P) abnormality who had more comprehensive medical history from 2013 to 2018 were collected. The karyotype analysis of bone marrow chromosomes in patients was carried out by using chromosome R band banding technique. FGFR1 gene was detected by using fluorescence in situ hybridization (FISH).@*RESULTS@#Seven cases of FGFR1 gene abnormalities were decteted, including 3 cases of FGFR1 gene amplification, 2 cases of translocation, and 2 cases of deletion. Five patients with FGFR1 gene amplification or deletion not accompaned with eosinophilia, moreover the chromosome was a complex karyotype with poor prognosis; Two cases of FGFR1 gene translocation were non-complex chromosomal translocation and one of which survived for 6 years after bone marrow transplantation, the other chromosome karyotype showed no rearrangement of 8 short arm. However, FGFR1 gene rearrangement was confirmed by FISH analysis, which was a rare insertional translocation.@*CONCLUSION@#FGFR1 gene amplification or deletion often occur in cases with complex karyotype, which not accompany eosinophilia, moreover have poor prognosis. The patients with FGFR1 gene translocation accompany eosinophilia which is consistent with the clinical characteristics of myeloid / lymphoid neoplasms with FGFR1 abnormality. Karyotype analysis combined with FISH method can improve the detection of abnormal clones.

Establishment of Flow Cytometric Immunobead Array for Detecting Plasma Von Willebrand Factor Activity and Its Clinical Application in the Prognosis of Ischemic Stroke / 中国实验血液学杂志

OBJECTIVE@#To establish a novel flow cytometric immunobead array (FCIA) for detecting plasma von Willebrand factor activity (vWF:GPIbR) and apply it in ischemic stroke (IS).@*METHODS@#Microspheres coated with anti-human platelet glycoprotein Ibα (GPIbα) monoclonal antibody SZ151 IgG, were incubated with recombinant fragment of GPIbα, then added ristocetin and plasma, finally incubated with FITC-conjugated sheep-anti-human vWF IgG polyclonal antibody, and detected by flow cytometry. vWF antigen (vWF:Ag), vWF:GPIbR, and vWF collagen binding assay (vWF:CB) were also included for evaluating vWF levels in IS patients.@*RESULTS@#The intra-assay coefficient variations (CVs) and inter-assay CVs of FCIA were 7.7% and 13.5%, respectively. The slope of the linear regression was 0.9739 (r=0.855, P<0.001), and the Bland-Altman bias was 9.95%, indicating a good correlation between FCIA and ELISA. The FCIA had better sensitivity, specificity and accuracy as compared with those by ELISA (P<0.05). The levels of vWF:Ag, vWF:GPIbR and vWF:CB in IS patients were significantly higher in comparison with those in healthy controls (H=7.8, 6.4, 6.2, respectively, P<0.01), the level of vWF:GPIbR in IS patients positively correlated with levels of vWF:Ag, high-sensitivity C-reactive protein, Autar score and hospitalization time.@*CONCLUSION@#The FCIA for detecting plasma vWF:GPIbR is more specific and accurate than ELISA. The vWF:GPIbR is involved in the paroxysm of IS, which could be used to evaluate the risk of thrombosis in IS patients.

Myricetin blocks the activation,proliferation and secretion of cardiac fibroblasts induced by TGF-β / 医学研究生学报

Objective It is rarely reported whether myricetin inhibits the activation and function of cardiac fibroblasts and thereby prevents myocardial fibrosis. This study was to investigate the effects of myricetin on the activation,proliferation and secretion of cardiac fibroblasts and its possible molecular mechanisms. Methods Fibroblasts isolated from 1-3 days old rats were cultured and their activation,proliferation and secretion were induced with the transforming growth factor (TGF). The fibroblasts were incubated with myricetin at different concentrations of 1,3,10,30 and 100 μmol/L for 24 hours followed by detection of their proliferation with the CKK8 kit,the transcription levels of fibrotic factors by RT-PCR and the expression levels of α-SMA and signal proteins by immunoflu-orescence staining and Western blot,respectively. Results The expression of α-SMA was significantly up-regulated in the cardiac fi- broblasts of the rats in the TGF-β,30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups as compared with that in the control group (P<0.05) but down-regulated in the 30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups in com-parison with that in the TGF-β group (P<0.05). At 48 hours,the transcription levels of collagenⅠ,collagenⅢ,fibronectin and con-nective tissue growth factor were markedly higher in the TGF-β,30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups than in the control group (P<0.05) but lower in the 30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups than in the TGF-β group (P<0.05). The phosphorylation levels of smad2 and smad3 were remarkably elevated in the TGF-β,30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups and the expression of smad4 reduced in the TGF-β group as com-pared with the control group (P<0.05). The levels of smad2,smad3 and smad4 were all significantly decreased in the 30 μmol/L myr-icetin+TGF-β and the 100 μmol/L myricetin+TGF-β groups in comparison with the TGF-β group (P<0.05). Conclusion Myricetin suppresses the activation,proliferation and secretion of cardiac fibroblasts induced by TGF-β via inhibiting the smad signaling pathway.

Expression miRNAs in cancer associated fibroblasts of gastric cancer and their effects on the migration and invasion / 临床与实验病理学杂志

To investigate various microRNAs (miRNAs) expression levels in cancer associated fibroblasts (CAFs) of gastric cancer,and to explore the effects of miRNA214 in CAFs on the invasion and migration of gastric cancer cells.Methods The primary CAFs were isolated from human gastric tumor tissues,while the normal fibroblasts (NFs) were from adjacent normal gastric mucosa tissues.Real-time quantitative PCR (RT-PCR) was performed to detect the expression level of miRNAs in CAFs and NFs.The interaction model in vitro between CAFs and MGC-803 (a gastric cancer cell line) was established by Transwell chamber,and then the effects of miRNA-214 in CAFs on MGC-803 invasion and migration were analyzed.Results It was found that the expression level of 18kinds of miRNAs in CAFs was different.Moreover,the expression level of miRNA-214 in CAFs was most observably decreased compared with NFs.Further studies indicated that over-expression of miRNA-214 in CAFs could markedly inhibit the migration and invasion ability of gastric cancer cells in vitro.Conclusion The expression of miRNAs was different between CAFs and NFs,and the miRNA-214 expression in CAFs is markedly reduced compared with NFs.The over-expression of miRNA-214in CAFs could significantly inhibit the migration and invasion ability of gastric cancer cells.Therefore,miRNA-214 in CAFs might act as a tumor suppressor in gastric cancer progression.

Progress in PD-1/PD-L1 inhibitors combined with other approaches in the treatment of non-small cell lung cancer / 肿瘤

Recent insight into onco-immunology has led to the breakthrough in immunotherapy of non-small cell lung cancer (NSCLC). Specifically, the immune checkpoints such as programmed death-1 (PD-1)/ programmed death ligand-1 (PD-L1) have brought a new era in the treatment of NSCLC. To further improve the overall survival and benefit broader population, the multiple potential combinations with other therapeutic strategies based on PD-1/PD-L1 inhibitors are in clinical development. However, the screening of appropriate population, the monitoring of toxicity, and determination of the end point in the clinical trial are a series of challenges to be faced with. This article reviews the progress in PD-1/PD-L1 inhibitors as backbone to synergistically combine with the existing cancer treatments, including molecularly targeted therapy, chemotherapy, radiotherapy and other immunotherapy in NSCLC.

Differences between system-affiliated hospitals and freestanding hospitals and determinants of hospital integration in Shanghai / 上海第二医科大学学报

Objective To explore the differences in health care quality,scale,output,efficiency,cost and financial condition between freestanding secondary hospitals and system-affiliated secondary hospitals in Shanghai,and analyse the determinants of hospital integration. Methods Eleven upper secondary hospitals in Shanghai integrated between 2000 and 2004 were selected,and another 40 secondary hospitals (including 30 upper secondary hospitals and 10 middle secondary hospitals) without integration were served as controls. Using related data of 1999,Mann-Whitney U test was performed to analyse the differences between these two groups,and Logistic regression analysis was conducted to explore the determinants of hospital integration. Results There were significant differences in health care quality,scale,and output between these two groups (P0.05). It was revealed by Logistic regression analysis that health care quality,scale,output,and financial condition were determinants of integration. Conclusion System-affiliated secondary hospitals have advantages over freestanding hospitals in health care quality,scale,output and financial condition,and those with better health care quality,larger scale,larger output and better financial condition are more likely to be integrated by tertiary hospitals.

Effect of public hospitals vertical integration on scale economy in Shanghai / 上海第二医科大学学报

Objective To study the effect of public hospitals vertical integration on scale economy in Shanghai. MethodsA total of 401 samples of 67 hospitals from 1999 to 2004 in Shanghai were collected.Median regression was performed to estimate the multi-output cost function and marginal cost of discharge patients,and scale economies were calculated.Results The independent variables Beds,W,X1,X23,Region,Level,Y03,and Y04 were all predictors of cost.Conclusion Both integrated tertiary and secondary hospitals had scale economy before and after integration.Integration enhanced the output and improved the efficiency of integrated secondary hospitals.To some extent,patients were dispersed to secondary hospitals.

The SWOT analysis and strategic considerations for the present medical devices' procurement / 中国医疗器械杂志

In this paper, the SWOT analysis method is used to find out the internal strength, weakness, exterior opportunities and threats of the present medical devices' procurements in hospitals and some strategic considerations are suggested as "one direction, two expansions, three changes and four countermeasures".