Objective:To investigate the efficacy of a machine learning model based on radiomics of brain lesions on T 2WI in differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disorders (NMOSD). Methods:Totally 223 MS and NMOSD patients who were treated from January 2009 to September 2018 in Beijing Tiantan Hospital Affiliated to Capital Medical University, Donghu Branch of the First Affiliated Hospital of Nanchang University, Tianjin Medical University General Hospital, and Xuanwu Hospital of Capital Medical University were analyzed retrospectively, and according to the proportion of 7∶3, 223 patients were completely randomly divided into training set (156 cases) and test set (67 cases). A total of 74 patients with MS and NMOSD who were treated in Huashan Hospital Affiliated to Fudan University and China-Japan Friendship Hospital of Jilin University from January 2009 to September 2018 and in Xianghu Branch of the First Affiliated Hospital of Nanchang University from March 2020 to September 2021 were collected as an independent external validation set. All patients underwent brain cross-sectional MR T 2WI, radiomics features were extracted from T 2WI, and features were selected by max-relevance and min-redundancy and least absolute shrinkage and selection operator algorithms. Then various machine learning classifier models (logistic regression, decision tree, AdaBoost, random forest or support vector machine) were constructed to differentiate MS from NMOSD. The area under curve (AUC) of receiver operating characteristics was used to evaluate the performance of each classifier model in the training set, test set and external validation set. Results:Based on multi-center T 2WI, a total of 11 radiomics features related to the discrimination between MS and NMOSD were extracted and classifier models were constructed. Among them, the random forest model had the best efficiency in distinguishing MS from NMOSD, and its AUC values for distinguishing MS from NMOSD in the training set, test set and external validation set were 1.000, 0.944 and 0.902, with specificity of 100%, 76.9% and 86.0%, and sensitivity of 100%, 92.1% and 79.7%, respectively. Conclusion:The random forest model based on the radiomic features of T 2WI of brain lesions can effectively distinguish MS from NMOSD.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged ; Antibodies, Viral ; COVID-19/therapy* ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; Immunization, Passive ; Recombinant Fusion Proteins ; SARS-CoV-2

Objective: To optimize the pre-column derivation high performance liquid chromatography (HPLC) content determination method of D-mannose and D-glucose as well as the content determination method of narinhenin in Dendrobium officinale and D. huoshanense, and compare the contents of D-mannose,D-glucose and narinhenin between D. officinale and D. huoshanense. Method: A pre-column derivation HPLC method modified by Chinese Pharmacopoeia(Ch.P) 2015 was used to simultaneously determine the contents of D-mannose and D-glucose,with acetonitrile-0.02 mol·L^-1 ammonium acetate solution as mobile phase for gradient elution. Kromasil 100-5 C₁₈ was performed with the wavelength set at 250 nm,and the flow rate was 1 mL·min^-1;column temperature was 30℃. HPLC content determination of narinhenin was performed on Kromasil 100-5 C₁₈ with the acetonitrile-methanol-0.4% phosphoric acid solution as mobile phase for gradient elution,and the wavelength was set at 290 nm; the flow rate was 0.8 mL·min^-1,and column temperature was 40℃. Result: D-mannose and D-glucose showed a good linear relationship within the range of 0.15-3.0 μg and 0.075-2.25 μg (r=0.999 9); and their average recoveries were 99.01% (RSD 2.1%) and 101.69% (RSD 2.0%) respectively. In addition, the other methodological researches such as repeatability and durability all met the requirements. The contents of D-mannose(C_m),D-glucose(C_g) and sum of them (C_m+C_g) were 12.75%-36.40%,2.93%-18.39% and 19.23%-54.58% in 43 batch of D. officinale. Almost all of the results except very few samples reached the D-mannose standard in Ch.P 2015, and the total content of D-mannose and D-glucose was also up to the total polysccharide standard in Ch.P. The correlation between content and origin was not significant. The contents of D-mannose(C_m),D-glucose(C_g) and sum of them (C_m+C_g) were 14.33%-29.47%,6.64%-15.20%,and 25.73%-44.37% in 12 batch of D. huoshanense. These contents and ratio of peak areas of D-mannose to D-glucose (A_m/A_g) were within the scope of D. officinale's; in addition, their average contents were basically the same with those in D. officinale (about 33%).Next,naringenin showed a good linear relationship within the range of 0.020 8-0.832 0 μg (r=0.999 9),and its average recovery was 101.96% (RSD 1.8%). The content of naringenin was 0.053 2-0.122 4 mg·g^-1 (average value of 0.081 0 mg·g^-1) in 11 batch of D. officinale, slightly higher than 0.040 3-0.090 0 mg ·g^-1 (average value of 0.068 3 mg ·g^-1) in 7 batch of D. huoshanense. All of these results of narinfenin did not reach the content lower limit in Ch.P. Conclusion: The method used to determinate the content of D-mannose and D-glucose is reproducible, and their sum content is possible to substitute the total polysccaride determination (with higher errors) in D. officinale; monosaccharide content determination can be used for quantitative quality control of D. huoshanense. However, it could not distinguish D. officinale and D. huoshanense by determining the contents of polysccharide,D-glucose,D-mannose and narinhenin, and shall be combined with other specificity methods for further identification.

Background:The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma;therefore,the use of morcellation is limited in the USA.A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy.Methods:A national multicenter study was performed in China.From 2002 to 2014,33,723 cases were retrospectively selected.We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application.A total of 62 cases were finally pathologically confirmed as malignant postoperatively.Additionally,the medical records of the 62 patients were analyzed in details.Results:The proportion of postoperative malignancy after morcellation application was 0.18％ (62/33,723) for patients who underwent laparoscopic myomectomy.Nearly 62.9％ (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery.And,23 (37.1％) patients showed rapid growth at the final preoperative ultrasound.With respect to the pathological types,38 (61.3％) patients had detectable endometrial stromal sarcoma,13 (21.0％) had detectable uterine leiomyosarcoma,only 3 (3.2％) had detectable carcinosarcoma,and 5 (8.1％) patients with leiomyoma had an undetermined malignant potential.Conclusions:The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy.Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential,and morcellation should be avoided.

OBJECTIVETo evaluate the clinical effect of a 10-day sequential therapy which was made up of omeprazole, clarithromycin, amoxicillin-clavulanate and metronidazole for the eradication of Helicobacter pylori (Hp) infection in children.

METHODA total of 214 children with abdominal pain, who were confirmed to have Hp infection through endoscopy, biopsy, and Hp culture. The 214 cases were randomly divided into four groups. A 10-day sequential therapy group accepted omeprazole 0.8 - 1.0 mg/(kg·d) plus amoxicillin-clavulanate 50 mg/(kg·d) for five days and omeprazole 0.8 - 1.0 mg/(kg·d), clarithromycin 20 mg/(kg·d) and metronidazole 20 mg/(kg·d) for the remaining five days. The 7-day triple therapy group, 10-day triple therapy group and 14-day triple therapy group received omeprazole 0.8 - 1.0 mg/(kg·d), amoxicillin-clavulanate 50 mg/(kg·d) and clarithromycin 20 mg/(kg·d) for 7 days,10 days,14 days, respectively. All drugs were given twice daily. All these patients received (13)C urea breath test ((13)C-UBT) four weeks after the treatment.

RESULTFinally, 199 patients were followed up, and the total rate of loss to follow-up was 7.0% (15/214). Hp eradication rate was 85.2% and 90.2% in the 10-day sequential therapy group on intention to treat (ITT) and per protocol (PP) analyses, 66.0% and 71.4% in the 7-day triple therapy group on ITT and PP analyses; 60.0% and 67.3% in 10-day triple therapy group on ITT and PP analyses, and 78.8% and 82.0% in patients who received the 10-day sequential regimen on ITT and PP analyses, respectively. By ITT analysis, there was significantly difference between the 10-day sequential therapy group and 7-day or 10-day triple therapy group (P < 0.05), while no significant difference was found between the 10-day sequential therapy group and 14-day triple therapy group (P > 0.05). The results of the ITT analysis and the PP analysis were the same. The four groups had neither significant difference in abdominal pain relief (P > 0.05) nor in incidence of adverse reactions (P > 0.05).

CONCLUSIONThe 10-day sequential regimen was significantly more effective than both 7-day triple regimen and 10-day triple regimen, while had the same eradication rate compared with the 14-day sequential therapy. But 10-day triple regimen to eradicate Hp infection in children had the advantages such as short course of treatment and better compliance.

Administration, Oral ; Adolescent ; Amoxicillin ; administration & dosage ; adverse effects ; Anti-Bacterial Agents ; administration & dosage ; adverse effects ; Anti-Ulcer Agents ; administration & dosage ; Breath Tests ; methods ; Child ; Child, Preschool ; Clarithromycin ; administration & dosage ; adverse effects ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Helicobacter Infections ; drug therapy ; Helicobacter pylori ; drug effects ; isolation & purification ; Humans ; Male ; Metronidazole ; administration & dosage ; adverse effects ; Microbial Sensitivity Tests ; Omeprazole ; administration & dosage ; adverse effects ; Time Factors ; Treatment Outcome

BACKGROUNDFew studies have explored the inward sodium current (INa) kinetics of transitional cardiomyocytes. This study aimed to explore the kinetics of transitional cardiomyocytes types alpha and beta.

METHODSThe whole-cell patch clamp technique was used to study the rapid INa of isolated transitional cardiomyocytes in the Koch triangle of rabbit hearts.

RESULTSMaximal amplitude and density of INa in type alpha and type beta was (-1627 +/- 288) pA (alpha), (-35.17 +/- 6.56) pA/pF (beta) and (-3845 +/- 467) pA (alpha), (-65.64 +/- 10.23) pA/pF (beta) (P < 0.05). Steady state activation curves of INa, fitted to a Boltzmann distribution for both types, were sigmoid in shape. Half activation voltage and slope factors did not significantly differ between types at (-43.46 +/- 0.85) mV (alpha), (-41.39 +/- 0.47) mV (beta) or (9.04 +/- 0.66) mV (alpha), (11.08 +/- 0.89) mV (beta). Steady state inactivation curves of INa, fitted to a Boltzmann distribution in both types were inverse "S" shape. Half inactivation voltage and slope factors were (-109.9 +/- 0.62) mV (alpha), (-107.5 +/- 0.49) mV (beta) and (11.78 +/- 0.36) mV (alpha), (11.57 +/- 0.27) mV(beta), (P > 0.05), but time constants of inactivation were significantly different at (1.10 +/- 0.19) mV (alpha) and (2.37 +/- 0.33) ms (beta), (P < 0.05). Time constants of recovery from inactivation of INa for both types were (122.16 +/- 27.43) mV (alpha) and (103.84 +/- 28.97) ms (beta) (P < 0.05).

CONCLUSIONSTransitional cardiomyocytes in rabbit hearts show a heterogeneous, voltage gated and time dependent fast inward sodium current. Types alpha and beta show the features of INa similar to those in slow- and fast-response myocytes, with probably better automaticity and conductivity, respectively.

Animals ; Female ; Ion Channel Gating ; Kinetics ; Male ; Membrane Potentials ; Myocytes, Cardiac ; metabolism ; Rabbits ; Sodium Channels ; physiology

OBJECTIVETo summarize the reasons for bile duct injury (BDI) after laparoscopic cholecystectomy (LC), and to determine the effect of multiple treatment after BDI.

METHODSA retrospective cohort study was performed. The medical records of 110 patients diagnosed with BDI after LC from October 1993 to November 2007, in ten large hospitals in Guangdong of China, were reviewed.

RESULTSAmong 110 patients with BDI, 58 cases (52.7%) were local patients, whereas 52 cases (47.3%) were transferred from outside hospitals. Reasons for BDI following LC were: (1) Lack of experience of the LC operator (48.2%); (2) LC performed during acute cholecystitis (20.0%); (3) The structure of Calot triangle was unclear (15.5%); (4) Variable anatomical position (11.8%); (5) Intra-operation bleeding (4.5%). The commonest sites of injury were the choledochus and common hepatic duct (76.4%). Following BDI, endoscopic stenting or operative repair was performed in 106 patients. The overall success rate was 95.3% (101/106), with a mortality rate was 0.9% (1/106). Cholangitis occurred in 3.8% (4/106) cases. Choledocho-enterostomy operation was performed in almost 60.0% (63/106) cases, and the success rate was 93.7% (59/63). Endoscopic stenting or operative repair was performed immediately following BDI in 23.6% (25/106) patients, the success rate was 100%; and within 30 days in 63.2% (67/106) patients. Eighty-eight out of 106 patients who underwent repair were successful following the first operative procedure.

CONCLUSIONSFactors such as an un-experienced operator and unclear anatomical position were causes of BDI following LC. Early operative repair should be regarded as the treatment of choice, in patients diagnosed with BDI. Early refer to an experienced hepatobiliary operator ensures a high success rate.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bile Ducts ; injuries ; surgery ; Cholecystectomy, Laparoscopic ; adverse effects ; Female ; Humans ; Iatrogenic Disease ; Intraoperative Complications ; diagnosis ; etiology ; surgery ; Male ; Middle Aged ; Retrospective Studies

AIMTo investigate the effect of interleukin-8 (IL-8) on the differentiation and clonal expansion of 3T3-L1 preadipocyte during the differentiation period.

METHODSThe morphological changes of 3T3-L1 cells during differentiation after the treatment of IL-8 was observed by Oil-Red O staining. Glycerol-3-phosphate dehydrogenase (GPDH) activity was measured by a spectrophotometric method. MTT method and 3H-TdR incorporation were applied to examine the changes of cell proliferation and DNA synthesis in clonal expansion of 3T3-L1 cells. Cell cycle analysis was taken by flow cytometry.

RESULTSIL-8 could inhibit the differentiation and GDPH activity in a dose dependent manner. IL-8 decreased the cell proliferation and DNA synthesis in clonal expansion after induction. Also, the proportion of cells in G1 phase was increased and that of cells in S and G2 phase was declined after the treatment of IL-8.

CONCLUSIONIL-8 inhibits the differentiation of 3T3-L1 preadipocytes by decreasing the clonal expansion of the cells.

3T3-L1 Cells ; Adipocytes ; cytology ; metabolism ; Animals ; Cell Cycle ; Cell Differentiation ; Cell Proliferation ; drug effects ; Interleukin-8 ; pharmacology ; Mice

OBJECTIVETo investigate the relationship between microdeletion of azoospermia factor (AZF) and male infertility.

METHODSMultiplex PCR was used to detect Y chromosome microdeletion in AZFa, AZFb and AZFc in 103 cases of idiopathic azoospermia, 72 cases of severe idiopathic oligozoospermia, and 60 healthy male controls.

RESULTSNo microdeletion was found in 60 controls. Y chromosome microdeletion was found in 19 of 175 azoospermia patients, the total prevalence rate of microdeletion was 10.9%. There were 15 cases (11 for azoospermia, 4 for severe oligozoospermia) in AZFc (8.6%), 3 cases (1 for azoospermia, 2 for severe oligozoospermia) in AZFb+c (1.7%), 1 case (azoospermia) in AZFa+b+c (0.6%). According to statistics, the difference of microdeletion rate between two groups was significant(P < 0.01).

CONCLUSIONY chromosome microdeletions is an important reason of azoospermia. Screening of Y chromosome microdeletions for azoospermia patients before intracytoplasmic sperm injection treatment is essential.

Adult ; Asian Continental Ancestry Group ; genetics ; Azoospermia ; diagnosis ; genetics ; Case-Control Studies ; China ; Chromosome Deletion ; Chromosomes, Human, Y ; genetics ; Female ; Genetic Loci ; Genetic Testing ; Humans ; Infertility, Male ; diagnosis ; genetics ; Male ; Middle Aged ; Oligospermia ; diagnosis ; genetics ; Seminal Plasma Proteins ; genetics