ObjectiveGastric cancer (GC) seriously affects human health and life, and research has shown that it is closely related to the serine/glycine metabolism. The proliferation ability of tumor cells is greatly influenced by the metabolism of serine and glycine. The aim of this study was to investigate the molecular mechanism of serine/glycine metabolism can affect the proliferation of gastric cancer cells. MethodsIn this work, a stable metabolic dynamic model of gastric cancer cells was established via a large-scale metabolic network dynamic modeling method in terms of a potential landscape description of stochastic and non-gradient systems. Based on the regulation of the model, a quantitative analysis was conducted to investigate the dynamic mechanism of serine/glycine metabolism affecting the proliferation of gastric cancer cells. We introduced random noise to the kinetic equations of the general metabolic network, and applied stochastic kinetic decomposition to obtain the Lyapunov function of the metabolic network parameter space. A stable metabolic network was achieved by further reducing the change in the Lyapunov function tied to the stochastic fluctuations. ResultsDespite the unavailability of a large number of dynamic parameters, we were able to successfully construct a dynamic model for the metabolic network in gastric cancer cells. When extracellular serine is available, the model preferentially consumes serine. In addition, when the conversion rate of glycine to serine increases, the model significantly upregulates the steady-state fluxes of S-adenosylmethionine (SAM) and S-adenosyl homocysteine (SAH). ConclusionIn this paper, we provide evidence supporting the preferential uptake of serine by gastric cancer cells and the important role of serine/glycine conversion rate in SAM generation, which may affect the proliferation ability of gastric cancer cells by regulating the cellular methylation process. This provides a new idea and direction for targeted cancer therapy based on serine/glycine metabolism.

OBJECTIVE To evaluate the effictiveness and safety of recombinant human endostatin combined with afatinib and teggio in the treatment of advanced lung squamous cell carcinoma. METHODS A total of 25 patients with driver-negative advanced lung squamous cell carcinoma were included in this single-arm prospective study, and the enrolled patients were treated with recombinant human endostatin combined with afatinib and teggio as scheduled. Progression-free survival(PFS), overall survival(OS), disease control rate(DCR), objective response rate(ORR), and adverse reactions(AR) were observed and analyzed. RESULTS The 25 enrolled patients received at least 2 cycles of second-line treatment, and were followed up as of March 31, 2023. Among them, 4 patients had partial remission, 17 patients had stable disease, and 4 patients experienced progressive disease. The ORR confirmed by the researchers was 16%(95%CI, 4.5%−36.1%), DCR was 84%(95%CI, 63.9%−95.5%), and median PFS was 5.3 months(95%CI, 3.5−6.9 months). The median OS had not yet been achieved. The entire group of patients had good treatment tolerance, and the most common level Ⅲ or Ⅳ adverse events related to treatment were leukopenia(20%) and rash(12%), with no reported treatment-related deaths. CONCLUSION Recombinant human endostatin combined with afatinib and teggio in the second line treatment of advanced lung squamous cell carcinoma can prolong the progression free survival period of patients and is relatively safe, which is worth further exploration and promotion.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

ObjectiveTo explore the effect of ovalbumin（OVA）-induced cough variant asthma （CVA） on the intestinal flora of mice， based on the traditional Chinese medicine theory of "exterior-interior relationship between the lung and the large intestine" and 16S ribosomal DNA gene sequencing technology. MethodsTwenty BALB/c female mice were randomly divided into model group and control group， and were sensitized and stimulated with OVA to establish a CVA mouse model. After modeling， the body weight and the cough response of mice were recorded by ammonia water-induced cough method. Hematoxylin-eosin staining was used to observe the pathological changes in the lungs of mice. The feces of mice were collected for 16S rDNA high-throughput sequencing analysis. ResultsCompared with the control group， the mice in the model group were in a poorer general state， being restless， scratching their ears， and losing weight （P<0.01）. The model group mice had increased cough times （P<0.01） and shortened cough latency （P<0.01） in comparison to the control group. Pathological results showed that the model group mice had obvious inflammatory infiltration， thickened airway smooth muscle， and epithelial cell necrosis. 16S ribosomal DNA sequencing showed that the species richness and diversity of the intestinal flora of mice in the model group increased， and the structure of the intestinal flora changed significantly. At the phylum level， the relative abundance of Firmicutes in the model group was decreased， and the relative abundance of Bacteroidetes and Euryarchaeota was increased. At the genus level， the relative abundance of Lactobacillus was decreased in the model group， and the relative abundance of Methanobrevibacter and Prevotellaceae UCG-003 was increased. ConclusionOVA-induced CVA mice had intestinal flora disorder， which provides new idea for the treatment of CVA， and further enriches the traditional Chinese medicine theory of “exterior-interior relationship between the lung and the large intestine”.

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

Objective: To explore current vitamin D status and influential factors of vitamin D deficiency and insufficiency among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China. Methods: According to the "province-city-hospital" sampling technical route, a total of 1 531 healthy children under 7 years of age were sampled from 11 provinces, autonomous regions or municipalities in China by the cluster random sampling method from November 2020 to November 2021. The demographic information, family conditions, behavior and living habits and feeding behaviors were collected using unified questionnaire. Serum 25-hydroxyvitamin D(25(OH)D) levels were measured by liquid chromatography-tandem mass spectrometry. Serum 25(OH)D<30 nmol/L was considered deficient and 30-50 nmol/L was considered insufficient. With 25(OH)D≤50 nmol/L as the dependent variable, multivariate Logistic regression was applied to analyze the association between vitamin D deficiency and insufficiency and potential influential factors. Results: The prevalence of vitamin D deficiency and insufficiency among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China was 14.0% (215/1 531), 3.8% (25/664) and 21.9% (190/867) in 0-<3 and 3-<7 of age years, respectively. Compared to children aged 0-<3 years, children aged 3-<7 years had a 2.6-fold increased risk of vitamin D deficiency and insufficiency (OR=3.60, 95%CI 1.93-6.72, P<0.001). Frequent sunlight exposure (OR=0.46, 95%CI 0.29-0.73, P=0.001), vitamin D supplementation (sometimes, OR=0.33, 95%CI 0.21-0.51, P<0.001; daily, OR=0.20, 95%CI 0.11-0.36, P<0.001) and infant formula intake(4-7 times per weeks, OR=0.43, 95%CI 0.28-0.68, P<0.001) were protective factors for vitamin D deficiency and insufficiency. Conclusion: Vitamin D deficiency and insufficiency are common among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China, which is affected by age, sunlight exposure, vitamin D supplementation and infant formula intake.
Child ; China/epidemiology* ; Cross-Sectional Studies ; Humans ; Infant ; Vitamin D ; Vitamin D Deficiency/epidemiology* ; Vitamins

The global pandemic of coronavirus disease 2019 (COVID-19) has brought great challenges to the traditional medical model. During the outbreak of COVID-19 in Shanghai, China, from March to May, 2022, there was a significant increase in the number of pediatric cases due to high transmissibility, immune escape, and vaccine breakthrough capacity of Omicron variants. The designated hospitals for children with COVID-19 served as a connecting link between children's specialized hospitals and mobile cabin hospitals. From April 7 to June 2, 2022, a total of 871 children with COVID-19 were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine (South Branch), a designated hospital for children with COVID-19. Among these patients, 568 (65.2%) were children under 3 years old, 870 (99.9%) were mild or moderate, and 1 was severe. This article reports the experience in the management of pediatric cases in this designated hospital, which included the following aspects: establishing an optimal case-admission process; strengthening multidisciplinary standardized diagnosis and treatment; optimizing the management, warning, and rescue system for severe COVID-19; implementing family-centered nursing care; formulating an individualized traditional Chinese medicine treatment regimen; optimizing the discharge process and strengthening bed turnover; implementing strict whole-process control to reduce the risk of nosocomial infection; constructing a structured medical record system and using information platforms to adapt to the work mode of large-volume cases; conducting scientific research and sharing the experience in diagnosis and treatment.
COVID-19 ; Child ; Child, Preschool ; China ; Hospitals, Pediatric ; Humans ; SARS-CoV-2

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Objective: To establish the norms and clinical application standards of mass spectrometry method to measure vitamin D in capillary blood. Methods: Following the "Province-City-Hospital" sampling procedure, a cross-sectional sample of 1 655 healthy children under 7 years of age were recruited from 12 provinces, autonomous regions, or municipalities in China from November 2020 to December 2021. Both venous and capillary blood samples from the same individual were collected, for which serum 25(OH)D levels were measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. Pearson correlation analysis and linear regression analysis were used to detect the correlation and determine a correction algorithm. The agreement was analyzed using Bland-Altman plot and Kappa statistic. The sensitivity and specificity were evaluated using receiver operating characteristic (ROC) curve method. Results: Venous and capillary 25(OH)D levels of 1 655 healthy children under 7 years of age were 74.25 (59.50, 92.00) and 68.75 (54.44, 86.25) nmol/L, respectively, showed a significant difference(Z=22.14, P<0.001) as well as a highly significant correlation between venous and capillary 25(OH)D levels(r=0.95, P<0.001). Linear regression analysis was then performed to determine the correction algorithm: lg(corrected capillary 25(OH)D)=0.13+0.95×lg(capillary 25(OH)D)(R²=0.90,P<0.001). The deviation between venous and corrected capillary 25(OH)D levels was (0.50±17.50) nmol/L, a difference value that did not reach statistical significance (P>0.05). The cut-off values of capillary blood 25(OH)D values 30.00, 50.00, 75.00 nmol/L corresponding to venous blood 25(OH)D values were 26.59, 45.56, and 69.84 nmol/L, respectively. Good consistency was observed between venous and corrected capillary 25(OH)D levels in clinical diagnosis (Kappa value 0.68-0.81). Corrected capillary 25(OH)D showed a high clinically predictive value (area under curve 0.97-0.99,sensitivity 0.72-0.92,specificity 0.89-0.99). Conclusion: The standardized capillary HPLC-MS/MS method can be used to detect 25(OH)D levels in children clinically.
Child ; Humans ; Vitamin D ; Cross-Sectional Studies ; Tandem Mass Spectrometry ; Vitamins ; Reference Standards