Comprehensive analysis of insulin products complex disulfide bonds structure by high resolution mass spectrum / 药学学报

The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Selection of chemical markers for identification of different species of Juniperri Caulis et Folium based on UPLC-Q-TOF-MS/MS metabonomics technology / 药学学报

In this study, untargeted metabolomics technology based on ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) was used to analyze and identify the overall chemical components of Juniperri Caulis et Folium. Chemical markers for the identification of different Juniperri Caulis et Folium species were screened by integrated principal component analysis and partial least squares discriminant analysis. A total of 58 chemical components were detected and 46 of them were identified, including 26 flavonoids, 8 organic acids and their derivatives, 4 phenylpropanoids, 3 terpenoids, and 5 other components. Among them, methylsyringin and ekersenin were identified for the first time. In the positive ion mode, 12 markers were screened, and in the negative ion mode, 13 markers were screened for species identification. In summary, UPLC-Q-TOF-MS/MS metabonomics technology combined with chemometrics method can effectively reveal the chemical composition differences of different Juniperri Caulis et Folium species, and provide reference for its species identification and quality control.

Mechanism of Fructus Lycii against dry eye: an analysis based on network pharmacology and experimental verification / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the mechanism of fructus lycii in treating dry eye based on network pharmacology and experimental verification.METHODS: Taking “fructus lycii” as key words, the active ingredients and target of fructus lycii were searched by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Gene targets related to dry eye(DE)were searched by GeneCards and OMIM databases. The target genes of fructus lycii and DE were imported into Venn software to obtain the intersection target map of them. After that, the data were imported into the String database to obtain the PPI protein-protein interaction network diagram. Using Cytoscape3.7.2 software, the PPI protein-protein interaction network diagram was constructed for active ingredients, target sites and related diseases of fructus lycii. The Bioconductor platform and R language were used for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis. And the key targets in the pathogenesis of DE were verified by experiments.RESULTS: Through TCMSP, 45 types of effective chemical components of fructus lycii, 174 target genes corresponding to active components and 131 common target genes with DE were screenedout. In accordance with the network topology of “drug-composition-disease-target”, 27 main effective components of fructus lycii were found in the treatment of DE. The PPI network was analyzed according to the high degree value, which is the key targets of fructus lycii for DE treatment, mainly including AKT1, VEGFA, CASP3, IL1B, JUN, PTGS2, CXCL8, etc. According to GO enrichment analysis, 166 biological functions and processes of fructus lycii for DE treatment were obtained. KEGG enrichment analysis showed that 31 signaling pathways were involved. Additionally, experimental verification displayed that the protein expressions of AKT1, interleukin-6(IL-6), tumor necrosis factor(TNF-α)and IL-17 in conjunctiva tissue of the DE model group were significantly increased.CONCLUSIONS: Through network pharmacology, this study confirmed that the treatment of DE by fructus lycii is a complex process involving multi-components, multi-targets and multi-pathways, and that the treatment of DE by fructus lycii is mainly regulated by anti-inflammatory and apoptosis-related molecules.

A novel and low-toxic peptide DR3penA alleviates pulmonary fibrosis by regulating the MAPK/miR-23b-5p/AQP5 signaling axis

Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH2) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH2) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.

Disease burden attributable to alcohol consumption in China in1990 and 2019 / 公共卫生与预防医学

Objective To compare and analyze the disease burden caused by drinking in China in 1990 and 2019. Methods The global disease burden database 2019 was used to analyze the attribution score (PAF), mortality, disability adjusted life year (DALY) and other indicators attributed to drinking in China in 1990 and 2019. The disease burden caused by alcohol consumption was compared between China and the world as well as different social demographic index (SDI) regions. Results From 1990 to 2019, the PAF attributed to drinking increased by 12.85%. The number of deaths attributed to drinking increased to 514 700, and the mortality increased to 36.18/100 000, while the DALY attributed to drinking increased to 17.2651 million person-years, and the DALY rate increased by 5.16%. The disease burden attributed to drinking was higher in men than that in women, and the attributable mortality and DALY rate in the elderly over 70 years old were higher than those in the young. From 1990 to 2019, the attributable disease burden of esophageal cancer was the highest in China, followed by colorectal cancer. Compared with the world and different SDI regions, China had the lowest standardized DALY rate attributed to drinking. Conclusion Drinking is one of the important risk factors for related diseases and cancers in China, and effective intervention measures should be taken for key populations.

Research progress of FAPI PET/CT in the diagnosis of malignant liver tumors / 中华肝脏病杂志

Malignant liver tumors have a high incidence and mortality rate. Therefore, it is of great significance to promptly learn about tumor advancement status through relevant examinations for patients' follow-up, diagnosis, and therapy as well as the improvement of the five-year survival rate. The primary lesions and intrahepatic metastases of malignant liver tumors have been better demonstrated in the clinical study with the use of various isotope-labeled fibroblast activating protein inhibitors because of their low uptake in liver tissues and high tumor/background ratio, which provides a new method for early diagnosis, precise staging, and radionuclide therapy. In light of this context, a review of the research progress of fibroblast-activating protein inhibitors for the diagnosis of liver malignant tumors is presented.

Advances in hepatitis E epidemiology / 中华肝脏病杂志

Hepatitis E is a viral hepatitis that the hepatitis E virus (HEV) causes. In the early 1980s, the hepatitis E virus was first discovered and identified, and it is one of the important pathogens that cause acute viral hepatitis globally. HEV infection is usually self-limiting, but in some groups of populations, such as pregnant women, patients with chronic liver disease, and the elderly, the prognosis is poor and may result in acute or subacute liver failure or even death. In addition, HEV infection can occur in chronically immunocompromised populations. At present, some regions and countries are not paying enough attention to hepatitis E prevention, diagnosis, and treatment, which suggests that we should study the epidemiology of HEV infection.

Three-dimensional finite element study on the effects of maxillary anterior two-step retraction and en-masse retraction with clear aligners / 中华口腔医学杂志

Objective: To investigate the effects of two-step retraction and en-masse retraction on tooth movement pattern of anterior teeth and posterior anchorage with clear aligners using three-dimensional finite element analysis. Methods: A finite element model of maxillary first premolar extraction case undergoing clear aligner treatment was established based on maxillofacial cone-beam CT data of a 24-year-old adult male with individual normal occlusion, who visited Department of Oral Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine for impacted mandibular third molar in June, 2022. The initial tooth displacement of five anterior retraction protocols (two-step with canine retraction, two-step with incisor bodily retraction, two-step with incisor retraction-overtreatment, en-masse bodily retraction, and en-masse retraction-overtreatment) were evaluated. Results: Two step with canine retraction caused distal tipping of the canine and labial tipping of the incisors (0.18° for central incisor and 0.13° for lateral incisor). Two step with incisor retraction caused mesial tipping of the canine. In two step with bodily retraction protocol, uncontrolled lingual tipping was found in central incisor (0.29°) and lateral incisor (0.32°). In two-step with incisor retraction-overtreatment protocol, the movement pattern of the incisors didn't change, but the inclinations reduced to 0.21° and 0.18°. En-masse retraction caused distal tipping of the canine. In en-masse bodily retraction protocol, uncontrolled lingual tipping was also found in central incisor (0.19°) and lateral incisor (0.27°). In en-masse retraction-overtreatment protocol, the central incisor showed controlled lingual tipping (0.02°) and the lateral incisor showed palatal root movement (0.03° labial inclination). Posterior teeth exhibited mesial tipping in all five protocols. Conclusion: En-masse retraction with incisor overtreatment was beneficial to incisor torque control in clear aligner treatment.

Value of glycosylated hemoglobin A1c and apolipoprotein A-1 ratio on predicting outcome of patients with acute coronary syndrome / 中华心血管病杂志

Objective: To investigate the predictive value of glycosylated hemoglobin A1c/apolipoprotein A-1 (HbA1c/ApoA-1) ratio for major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS). Methods: The present study is a retrospective cohort study. ACS patients who were hospitalized and underwent coronary angiography at Beijing Hospital from March 2017 to March 2019 were enrolled. Baseline information such as sex, age, previous history, Gensini score, HbA1c and ApoA-1 were analyzed. Patients were divided into two groups according to presence or absence of MACEs and the difference on HbA1c/ApoA-1 ratio was compared between the two groups. According to the tertiles of HbA1c/ApoA-1 levels, patients were divided into high (5.87-16.12), medium (4.50-5.83) and low (2.11-4.48) HbA1c/ApoA-1 groups. Cox proportional risk model was used to evaluate the differences in MACEs and all-cause mortality among the three groups. Kaplan-Meier survival analysis was used to compare the differences of MACEs between the various HbA1c/ApoA-1 groups. Results: A total of 366 ACS patients were included in this study. The mean age of the patients was (65.9±10.3) years. There were 59 MACEs and 10 all-cause deaths during the mean of (22.3±4.4) months follow-up. After adjusting for age, systolic blood pressure, history of diabetes and Gensini score, the incidence of MACEs was 2.45 times higher in the high HbA1c/ApoA-1 group than in the low HbA1c/ApoA-1 group (95%CI 1.16-5.18, P=0.019). There was no significant difference in all-cause mortality between the high and low HbA1c/ApoA-1 groups (P=1.000). Kaplan-Meier survival analysis showed that patients in the high HbA1c/ApoA-1 group had the highest risk of MACEs, while patients in the low HbA1c/ApoA-1 group had the lowest risk of MACEs (P<0.01). Spearman rank correlation analysis showed that HbA1/ApoA-1 ratio was positively correlated with Gensini score in ACS patients (r=0.274, P<0.01). Conclusion: High HbA1c/ApoA-1 ratio was an independent risk factor for MACEs in ACS patients. Patients with high HbA1c/ApoA-1 ratio had more severe coronary artery disease lesions. HbA1c/ApoA-1 ratio may be used as a potential risk stratification biomarker for ACS patients, it might be useful for the early identification of high-risk population and for predicting the incidence of MACEs among ACS patients.

Methamphetamine: Mechanism of Action and Chinese Herbal Medicine Treatment for Its Addiction / 中国结合医学杂志

With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.

Clinical Characteristics and Nomogram Model of Nosocomial Infection in Patients with Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics of nosocomial infection in newly diagnosed multiple myeloma(NDMM) patients, and establish a predictive nomogram model.@*METHODS@#The clinical data of 164 patients with MM who were treated in Shanxi Bethune Hospital from January 2017 to December 2021 were retrospectively analyzed. The clinical characteristics of infection were analyzed. Infections were grouped as microbiologically defined infections and clinically defined infections. Univariate and multivariate regression models were used to analyze the risk factors of infection. A nomogram was established.@*RESULTS@#164 patients with NDMM were included in this study, and 122 patients (74.4%) were infected. The incidence of clinically defined infection was the highest (89 cases, 73.0%), followed by microbial infection (33 cases, 27.0%). Among 122 cases of infection, 89 cases (73.0%) had CTCAE grade 3 or above. The most common site of infection was lower respiratory in 52 cases (39.4%), upper respiratory tract in 45 cases (34.1%), and urinary system in 13 cases (9.8%). Bacteria(73.1%) were the main pathogens of infection. Univariate analysis showed that ECOG ≥2, ISS stage Ⅲ, C-reactive protein ≥10 mg/L, serum Creatinine ≥177 μmol/L had higher correlation with nosocomial infection in patients with NDMM. Multivariate regression analysis showed that C-reactive protein ≥10 mg/L (P＜0.001), ECOG ≥2 (P=0.011) and ISS stage Ⅲ （P=0.024） were independent risk factors for infection in patients with NDMM. The nomogram model established based on this has good accuracy and discrimination. The C-index of the nomogram was 0.779（95%CI: 0.682-0.875）. Median follow-up time was 17.5 months, the median OS of the two groups was not reached (P=0.285).@*CONCLUSION@#Patients with NDMM are prone to bacterial infection during hospitalization. C-reactive protein ≥10 mg/L, ECOG ≥2 and ISS stage Ⅲ are the risk factors of nosocomial infection in NDMM patients. The nomogram prediction model established based on this has great prediction value.

Clinical Anslysis of Primary Adrenal NK/T-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma.@*METHODS@#The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed.@*RESULTS@#Combined with pathology, imaging, bone marrow examination， etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen（gemcitabine 1 g/m2 d1 + oxaliplatin 100 mg/m2 d 1 + etoposide 60 mg/m2 d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5） was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later.@*CONCLUSION@#PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.

Network Meta-analysis of oral Chinese patent medicine in adjuvant treatment of rotavirus gastroenteritis in children / 中国中药杂志

This study aimed to evaluate the efficacy and safety of various oral Chinese patent medicines in the adjuvant treatment of rotavirus gastroenteritis(RVGE) in children based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicine in the adjuvant treatment of RVGE in children was retrieved from the databases such as CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science from database inception to October 22, 2022. The quality of the included RCT was evaluated according to the Cochrane risk-of-bias tool, and the data were analyzed by RevMan 5.4 and Stata 16 software. Sixty-three RCTs were included, with 11 oral Chinese patent medicines involved, including Xingpi Yanger Granules, Weichang'an Pills, Qiuxieling Mixture, Erxieting Granules, and Changyanning Granules/Syrup. The results of the network Meta-analysis showed that in terms of clinical total effective rate, the top 3 optimal interventions were Changyanning Granules/Syrup, Xiaoer Guangpo Zhixie Oral Liquid, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of the anti-diarrheal time, the top 3 optimal interventions were Shenling Baizhu Granules, Qiuxieling Mixture, and Shuangling Zhixie Oral Liquid combined with conventional western medicine. In terms of the antiemetic time, the top 3 optimal interventions were Changyanning Granules/Syrup, Xingpi Yanger Granules, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of the antipyretic time, the top 3 optimal interventions were Shenling Baizhu Granules, Xiaoer Shuangjie Zhixie Granules, and Qiuxieling Mixture combined with conventional western medicine. In terms of the negative conversion rate of rotavirus, the top 3 optimal interventions were Xingpi Yanger Granules, Erxieting Granules, and Cangling Zhixie Oral Liquid combined with conventional western medicine. In terms of reducing creatine kinase isoenzyme MB(CK-MB) level, the top 3 optimal interventions were Weichang'an Pills, Xingpi Yanger Granules, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of adverse reactions, no se-rious adverse reactions were reported in all studies. Oral Chinese patent medicines in the adjuvant treatment of children with RVGE have their own advantages, Specifically, Changyanning Granules/Syrup + conventional western medicine focuses on improving the clinical total effective rate and shortening the antiemetic time, Shenling Baizhu Granules + conventional western medicine on shortening the anti-diarrheal time and antipyretic time, Xingpi Yanger Granules + conventional western medicine on improving the negative conversion rate of rotavirus, and Weichang'an Pills + conventional western medicine on reducing the CK-MB level. Limited by the quantity and quality of literature included in this study, the results need to be verified by high-quality RCT with a larger sample size.

Associations of sex hormone levels with body mass index (BMI) in men: a cross-sectional study using quantile regression analysis / 亚洲男科学杂志(英文版)

Body mass index (BMI) has been increasing globally in recent decades. Previous studies reported that BMI was associated with sex hormone levels, but the results were generated via linear regression or logistic regression, which would lose part of information. Quantile regression analysis can maximize the use of variable information. Our study compared the associations among different regression models. The participants were recruited from the Center of Reproductive Medicine, The First Hospital of Jilin University (Changchun, China) between June 2018 and June 2019. We used linear, logistic, and quantile regression models to calculate the associations between sex hormone levels and BMI. In total, 448 men were included in this study. The average BMI was 25.7 (standard deviation [s.d.]: 3.7) kg m-2; 29.7% (n = 133) of the participants were normal weight, 45.3% (n = 203) of the participants were overweight, and 23.4% (n = 105) of the participants were obese. The levels of testosterone and estradiol significantly differed among BMI groups (all P < 0.05). In linear regression and logistic regression, BMI was associated with testosterone and estradiol levels (both P < 0.05). In quantile regression, BMI was negatively associated with testosterone levels in all quantiles after adjustment for age (all P < 0.05). BMI was positively associated with estradiol levels in most quantiles (≤80th) after adjustment for age (all P < 0.05). Our study suggested that BMI was one of the influencing factors of testosterone and estradiol. Of note, the quantile regression showed that BMI was associated with estradiol only up to the 80th percentile of estradiol.

Effects of luminous environments on visual performance of people with different vision / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the effects of the specific simulated luminous environment on the visual performance of people with different vision, so as to provide an experimental basis for revising pilots' vision standards. METHODS: A controlled randomized trial was conducted. Twenty-four volunteers were recruited and divided into four groups(1.0/1.0, 0.8/0.8, 0.6/0.6 and 0.4/0.4, decimal vision)according to right/left eye visual acuity, with six subjects in each group. Each subject was tested for static distant vision, kinetic visual acuity, color vision, depth perception error and visual search time under the simulated luminous environments of sunlight, twilight, and on-cloud, respectively, to compare changes in the impact of distinctive luminous surroundings on the visual performance indicators of human beings with different vision.RESULTS: There were main effect differences in static distant vision, kinetic visual acuity, color error, depth perception error and visual search time under different light environments(all P&#x003C;0.01). The binocular static distant visual acuity, abilities of color discrimination, depth perception and visual search in simulated sunlight environment were higher than those in simulated twilight and on-cloud environments. In the 0.4/0.4 vision group, kinetic vision in simulated twilight and on-cloud environments were significantly lower than that in simulated sunlight environment(P&#x003C;0.01). There were main effect differences in binocular static distant vision, kinetic visual acuity, depth perception error and visual search time among subjects with different vision(all P&#x003C;0.05). Compared with 1.0/1.0 vision group, those with 0.6/0.6 and 0.4/0.4 vision had significant decrease in kinetic visual acuity, depth perception ability and visual search ability(all P&#x003C;0.05). CONCLUSION: Different luminous environments have a great impact on the visual performance of people with low vision, which poses a potential threat to flight safety.

Resibufogenin suppresses human hepatocellular carcinoma cell proliferation, migration and invasion in vitro / 药学学报

This manuscript aims to investigate the effects of resibufogenin on the proliferation, migration and invasion of human hepatocellular carcinoma cells and its related mechanisms. MTT assay was used to determine the inhibitory effect of resibufogenin on the growth of four hepatocellular carcinoma cells in vitro. Wound-healing assay and Transwell assay were used to evaluate the migration and invasion ability of resibufogenin on MHCC-97H cells. Western blot assay was used to detect the expression of migration and invasion related proteins in MHCC-97H cells treated with different concentrations of resibufogenin. The results showed that resibufogenin significantly inhibited the proliferation of hepatocellular carcinoma cells in vitro. The half maximal inhibitory concentration (IC50) values on MHCC-97H, HepG2, SK-Hep-1 and Huh-7 cells were 0.55 ± 0.06, 2.83 ± 0.24, 5.25 ± 0.49, 14.89 ± 2.28 μmol·L-1, respectively. Resibufogenin also suppressed the migration and invasion of MHCC-97H cells in a concentration-dependent manner. The protein expression of integrin α2, integrin α6, integrin β1, N-cadherin, matrix metalloproteinase 2 (MMP2) and transcription factor Twist in MHCC-97H cells were decreased significantly with the increase of the concentration of resibufogenin, while the protein expression of E-cadherin increased. In addition, we found that p-PI3K/PI3K and p-AKT/AKT ratios were significantly reduced after treatment with resibufogenin. In conclusion, resibufogenin can inhibit the proliferation, migration and invasion of hepatocellular carcinoma MHCC-97H cells in vitro, which is related to the regulation of intracellular migration and invasion protein expression and PI3K/AKT signaling pathway.

Accuracy of photogrammetry and conventional impression techniques for complete-arch implant rehabilitation: an in vitro comparative study / 中华口腔医学杂志

Objective: To compare the accuracy of photogrammetry and conventional impression techniques for complete-arch implant rehabilitation. Methods: An edentulous maxillary stone cast containing 8 screw-retained implant abutment replicas was derived from a 74-year-old male patient who visited the Department of Dental Implant Center, Capital Medical University School of Stomatology in September 2019. The stone cast was copied through the open-tray splinted impression, and the copied cast was used as the master cast for this study. The abutment-level impressions of master cast were made by photogrammetry (PG) and the conventional impression technique (CNV) by one attending doctor. Group PG: after which scan bodies were connected to each implant replica, a photogrammetry system was used to obtain digital impressions of the master cast (n=10); Group CNV: conventional open-tray splinted impression technique was performed to fabricate conventional definitive casts (n=10). After connecting the scan bodies onto each implant replicas, the master cast and the 10 definitive casts from group CNV were digitized with a laboratory reference scanner. All data of group PG, group CNV and mater cast were saved as ".stl" files. For all test scans and reference scan, the three-dimensional information of scan bodies were converted to implant abutment replicas using a computer aided design software (Exocad). The data of the group PG and the group CNV were respectively registered with the reference data (trueness analysis) and pairwise within group (precision analysis) for accuracy evaluation in a three-dimensional analysis software (Geomagic Control X). Results: The trueness and precision of group PG [(17.33±0.34) and (2.50±0.79) μm ] were significantly statistically better than those of group CNV [(24.30±4.16) and (26.12±4.54) μm] respectively (t=-5.29 and -34.35, P<0.001). Conclusions: For complete-arch implant abutment-level impression, photogrammetry produces significantly better accuracy than conventional impression technique.

Non-erythrocyte blood products transfusion in very preterm and extremely preterm infants in Chinese neonatal intensive care units / 中华儿科杂志

Objective: To describe the use of non-erythrocyte blood products transfusion in very preterm and extremely preterm infants in the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) in 2019, to explore the disparity between different centers, and to further investigate the rationality and standardability of non-erythrocyte blood products transfusion. Methods: This was a cross-sectional study based on the CHNN cohort of very preterm and extremely preterm infants. All 6 598 infants with gestational age (GA)<32 weeks and admitted to the 57 NICU of CHNN within 24 h of life in 2019 were enrolled. Non-erythrocyte blood products included platelet, plasma, albumin, immunoglobulin, cryoprecipitate and prothrombin complex. Infants who received at least one type of non-erythrocyte blood products were defined in transfusion group. The comparison between infants with and without transfusion was done by t-test, rank-sum test or χ2 test as appropriate. Linear regression model was used to generate adjusted transfusion rate of each center, and to investigate the correlation between adjusted rate and center-level characteristics. Results: A total of 6 598 infants were enrolled in the study, with gestational age of 30.0 (28.7, 31.0) weeks and birth weight of (1 353±312) g, and 43.6 % (2 877) of them were female. Among them, 42.7% (2 816) infants were enrolled in transfusion group, with the times of transfusion as 3 (1, 6) times. Compared to the infants without any transfusion of non-erythrocyte blood products, those infants received transfusion had lower gestational age (Z=17.62, P<0.01), lower birth weight (t=18.64, P<0.01), higher proportion of small-for-gestation age (χ2=31.06, P<0.01), multiple birth (χ²=12.82, P<0.01) and intensive resuscitation in delivery room (χ²=287.52, P<0.01), as well as lower proportion of females (χ²=10.68, P<0.01) and even lower proportion of infants born in this hospital (χ²=78.23, P<0.01). Among the entire study population, albumin (25.4%, 1 674 cases), immunoglobulin (21.5%, 1 417 cases) and plasma (18.9%, 1 245 cases) were the most commonly used non-erythrocyte blood products. Overall, 60.4% (544/901) infants with gestational age <28 weeks received transfusion 4 (2, 8) times. A total of 39.9% (2 272/5 697) infants between 28-31weeks received non-erythrocyte blood products 3 (1, 6) times. The non-erythrocyte blood products transfusion rates of critically-ill and non-critically-ill infants were 62.2% (1 693/2 723) and 29.0% (1 123/3 875) respectively, and the transfusion times were 4 (2,7) and 2 (1,4) times. The transfusion rates varied significantly among different NICU, and the disparities remained obvious after adjustment (adjusted χ²=153.48, P<0.01). Conclusion: Near half of very preterm and extremely preterm infants admitted to Chinese NICU in 2019 receive non-erythrocyte blood products during hospitalization with significant disparities among different hospitals.

Analysis on vaccination willingness and related factors of influenza, pneumonia, and herpes zoster vaccine among people over 50 years old in Minhang district of Shanghai / 中华预防医学杂志

Objective: To determine the knowledge of influenza, pneumonia, herpes zoster and related vaccines, willingness to vaccinate under multiple payment scenarios, and corresponding risk factors among people over 50 years old in Minhang District of Shanghai. Methods: A total of 1 672 respondents aged 50-69 from 13 communities/towns in Minhang district of Shanghai were included in this study using a stratified random sampling strategy on December 2020. The knowledge of influenza, pneumonia, herpes zoster and vaccines was investigated using a questionnaire, and the differences in the willingness under multiple payment scenarios were determined using chi-square test. The consistency in the willingness under multiple payment scenarios was compared using Cohen's Kappa and the risk factors of the willingness was determined using ordinal logistic regression. Results: The average age of 1 672 respondents was (60.48±5.96) years old, including 777 (46.47%) males and 895 (53.53%) females. A total of 1 350 subjects (80.74%) had local household registration in Shanghai. The proportion of the willingness to vaccinate for themselves, spouses, and parents under any payment scenario was determined to be 80.6% (influenza vaccine), 81.5% (pneumonia vaccine), and 74.0% (herpes zoster vaccine). The willingness to vaccinate against influenza and pneumonia under multiple payment scenarios remained stable (Kappa value ≥0.6), while that against herpes zoster infection was inconsistent (Kappa value ≤0.35). Logistic regression analysis showed that respondents who had higher knowledge of influenza and influenza vaccine [OR (95%CI): 1.111 (1.054-1.170), 1.182 (1.126-1.240), respectively], aged 50-59 [1.305 (1.085-1.531)] and local household registration in Shanghai [1.372 (1.079-1.721)] had higher willingness to vaccinate against influenza, while males had lower willingness [0.733 (0.551-0.910)]. Respondents who had higher knowledge of pneumonia and pneumonia vaccine [OR (95%CI): 1.837 (1.152-2.517), 2.217 (1.541-2.893), respectively] had higher willingness to receive pneumonia vaccine. Respondents aged 50-59 [1.327 (1.059-1.537)] and with local household registration in Shanghai [2.497 (1.417-4.400)] were more likely to be vaccinated against herpes zoster, while those with middle school degree or below [0.664 (0.396-0.992)] and high school degree [0.559 (0.324-0.964)] were less likely to be vaccinated. Conclusion: Among people aged over 50 years old in Minhang district of Shanghai, the willingness to vaccinate for themselves, spouses, and parents against influenza, pneumonia and herpes zoster infection is quite different under multiple payment scenarios, especially for herpes zoster vaccine.