Abstract On September 26, 2024, a municipal hospital in Jiaxing City reported a maternal case of Listeria monocytogenes infection. In order to clarify the source of infection, the Jiaxing Center for Disease Control and Prevention immediately conducted the epidemiological investigation, laboratory testing and related disposal work. The case presented with fever (37.9 ℃), gradually intensifying paroxysmal abdominal pain without obvious cause, and went to hospital on the day of onset. Due to fetal intrauterine distress, a male infant was delivered by cesarean section on the same day. The epidemiological investigation identified that the case usually consumed fruits, often store fruits such as watermelon and grapes in the refrigerator alongside raw meat, and the refrigerator had never been cleaned or disinfected, posing a risk of cross contamination. Laboratory tests on amniotic fluid sample from the pregnant woman, infant blood sample showed positive results for Listeria monocytogenes infection. One strain of Listeria monocytogenes was detected in a smear sample from the inner wall of the refrigerator, and all the strains were ST2 type. Consuming fruits contaminated with Listeria monocytogenes may be the main source of infection. Food safety education for pregnant women and their family members should be strengthened to reduce the risk of infection.

Objective:To summarize the clinical and genetic characteristics of pseudoachondroplasia and multiple epiphyseal dysplasia caused by COMP gene variants in pediatric patients.Methods:This retrospective study concluded 15 pediatric patients with COMP-related pseudoachondroplasia and multiple epiphyseal dysplasia at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from July 2013 to August 2024. This paper analyzed clinical manifestations, laboratory findings and genetic testing.Results:This cohort comprised 15 pediatric patients (8 males and 7 females) with a diagnostic age of 5.3 (1.8,9.3) years. The major clinical presentations included abnormal gait (15/15), brachydactyly (11/15), genu varum (12/15), irregular metaphyseal changes (14/14) and epiphyseal dysplasia (14/14). Genetic analysis revealed 13 cases of pseudoachondroplasia and 2 multiple epiphyseal dysplasias cases associated with COMP gene variants. Fifteen variants were identified (8 pathogenic and 7 likely pathogenic), including 2 novel variants (c.1223A>G, c.1378G>C). Thirteen of these patients had variations clustered in exons 8-14 encoding the calmodulin-like domains, with c.1414_1419dupGACGAC emerging as a hotspot variant.Conclusions:COMP-related pseudoachondroplasia and multiple epiphyseal dysplasia predominantly manifest with gait abnormalities and skeletal deformities. COMP gene pathogenic variations were mainly located in calmodulin-like domains.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

Objective To observe the efficacy of positive pressure oxygen therapy combined with drugs to improve pulmonary circulation in the treatment of severe viral pneumonia in high-altitude areas.Methods A two-way cohort study was conducted.Patients with severe viral pneumonia and those with common viral pneumonia complicated with underlying heart and lung diseases admitted to department of intensive care unit of Xizang Autonomous Region People's Hospital were selected as the research subjects.Patients who received conventional treatment in the early stage were assigned to the control group,while those who received conventional treatment plus active positive pressure oxygen therapy combined with drugs to improve pulmonary circulation in the later stage were assigned to the study group.The treatment effective rates of the two groups were observed(including the time for viral nucleic acid to turn negative,hospital stay,and 28-day follow-up mortality)and changes in cardiopulmonary function indicators[pulmonary artery pressure,tricuspid annular plane systolic excursion(TAPSE),left ventricular stroke volume(SV),and lung ultrasounol score(LUS)]before and after treatment were also observed,and the Kaplan-Meier curve was drawn to analyze the 28-day cumulative survival rate of the two groups.Results There was no statistically significant difference in the time for viral nucleic acid to turn negative and hospital stay between the two groups.Compared with the control group,the 28-day mortality in the study group was significantly lower[6.5%(2/31)vs.25.0%(13/52),P<0.05].Compared with before treatment,pulmonary artery pressure gradually decreased,TAPSE significantly increased,and left ventricular SV significantly increased after treatment in the study group,and the differences were statistically significant compared with 10 days after treatment[pulmonary artery pressure(mmHg,1 mmHg≈0.133 kPa):28.84±8.71 vs.34.68±10.76,TAPSE(cm):2.37±0.11 vs.2.03±0.41,SV(mL):68.68±7.17 vs.59.61±6.73,all P<0.01].Pulmonary lesions,especially bilateral pulmonary exudative lesions,significantly improved compared with before treatment,atelectasis improved significantly,and LUS significantly decreased(14.77±5.33 vs.20.32±5.63,P<0.01).Kaplan-Meier curve analysis showed that the 28-day cumulative survival rate in the study group was significantly higher than that in the control group(Log-Rank test:χ2=4.510,P=0.034).Conclusion Active use of positive pressure ventilation and early administration of drugs to improve pulmonary circulation in patients in high-altitude areas can significantly reduce pulmonary artery pressure and significantly improve left and right heart function and pulmonary exudative lesions.These improvements may reduce the mortality rate of viral pneumonia and viral infections complicated with underlying heart and lung diseases in high-altitude areas.

Objective To investigate the influencing factors of nutritional risk in patients with radia-tion-induced oral mucositis and establish a predictive model.Methods A total of 126 patients with nasopha-ryngeal carcinoma and radiation-induced oral mucositis who visited the General Hospital of Shaoxing Second Hospital Affiliated Healthcare Group,Dongpu Street Community Health Service Center in Yuecheng District,Shaoxing City,and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2020 to January 2023 were selected as the model group and divided into the nutritional risk group and the nutrition-ally normal group according to the presence or absence of nutritional risk.Meanwhile,54 patients with radia-tion-induced oral mucositis due to nasopharyngeal carcinoma from February 2023 to March 2024 were selected as the validation group.Logistic regression was used to establish a risk prediction model,and a nomogram was developed and validated.Results Multivariate analysis showed that digestive discomfort symptoms,dietary structure score,and anxiety were factors influencing nutritional risk in patients with radiation-induced oral mucositis.In the model group,the area under the ROC curve was 0.992(95%CI:0.977 to 1.000),the maxi-mum Youden index was 0.961,corresponding specificity was 0.961,sensitivity was 1.000,χ2=4.668,P=0.792.In the validation group,the area under the ROC curve was 0.948(95%CI:0.897 to 0.999),the maxi-mum Youden index was 0.742,corresponding specificity was 0.742,sensitivity was 1.000,χ2=4.438,P=0.816.The model demonstrated good predictive ability.Conclusion A predictive model for nutritional risk factors in patients with radiation-induced oral mucositis is successfully constructed and can provide clinical reference.

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective To investigate the mechanism of the miR-518a-5p/histone deacetylase 6(HDAC6)axis in DNA oxidative damage in ovarian cancer(OC)SKOV3 cells.Methods Expression levels of miR-518a-5p and HDAC6 mRNA in OC tissues and in various cancer cells(A2780,SKOV3,CAOV3)were detected by qRT-PCR.SKOV3 cells were separated into Control,miR-NC,miR-518a-5p mimics,miR-518a-5p mimics+pcDNA-NC,and miR-518a-5p mimics+pc-HDAC6 groups.Cell proliferation and apoptosis were analyzed by colony-forming assay and Hoechst 33258 staining.Expression of phosphorylated histone H2AX(γ-H2AX)was detected by immunofluorescence assay and reactive oxygen species(ROS)were detected by flow cytometry.HDAC6,Bcl-2-associated X protein(Bax),and B-cell lymphoma-2(Bcl-2)protein expression were analyzed by Western blot.The regulatory relationship between miR-518a-5p and HDAC6 was analyzed by dual luciferase assay.The effect and mechanism of miR-518a-5p on oxidative DNA damage in OC cells were studied in a xenotransplantation tumor model.Results miR-518a-5p expression was decreased and HDAC6 expression was increased in OC tissues and A2780,SKOV3,and CAOV3 cells(P＜0.001).Expression levels of miR-518a-5p were lowest and expression levels of HDAC6 were highest in SKOV3 cells,and SKOV3 cells were therefore selected for subsequent experiments.miR-518a-5p expression,apoptosis rate,number of γ-H2AX-positive cells,relative ROS fluorescence intensity,and expression of Bax were all higher in the miR-518a-5p mimics group compared with the miR-NC group,while HDAC6 mRNA and protein expression,Bcl-2 expression,and colony-formation number were all lower(P＜0.001).HDAC6 mRNA and protein expression,colony-formation number,and expression of Bcl-2 were higher in the miR-518a-5p mimics+pc-HDAC6 group compared with the miR-518a-5p mimics+pcDNA-NC group,and the apoptosis rate,number of γ-H2AX-positive cells,relative ROS fluorescence intensity,and expression of Bax were all lower(P＜0.001).HDAC6 had a targeted regulatory relationship with miR-518a-5p.Overexpression of miR-518a-5p decreased tumor volume,weight,and HDAC6 protein expression in tumor tissues,and increased γ-H2AX expression in vivo(P＜0.001).Upregulation of HDAC6 expression by overexpression of miR-518a-5p increased graft tumor volume,weight,and HDAC6 protein expression and decreased γ-H2AX-positive expression(P＜0.05).Conclusions miR-518a-5p expression is reduced and HDAC6 expression is increased in OC tissues and cells.Overexpression of miR-518a-5p can induce oxidative DNA damage in SKOV3 cells by inhibiting HDAC6 expression,thereby inhibiting cell proliferation and promoting cell apoptosis.

Objective:To summarize the clinical and genetic characteristics of pseudoachondroplasia and multiple epiphyseal dysplasia caused by COMP gene variants in pediatric patients.Methods:This retrospective study concluded 15 pediatric patients with COMP-related pseudoachondroplasia and multiple epiphyseal dysplasia at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from July 2013 to August 2024. This paper analyzed clinical manifestations, laboratory findings and genetic testing.Results:This cohort comprised 15 pediatric patients (8 males and 7 females) with a diagnostic age of 5.3 (1.8,9.3) years. The major clinical presentations included abnormal gait (15/15), brachydactyly (11/15), genu varum (12/15), irregular metaphyseal changes (14/14) and epiphyseal dysplasia (14/14). Genetic analysis revealed 13 cases of pseudoachondroplasia and 2 multiple epiphyseal dysplasias cases associated with COMP gene variants. Fifteen variants were identified (8 pathogenic and 7 likely pathogenic), including 2 novel variants (c.1223A>G, c.1378G>C). Thirteen of these patients had variations clustered in exons 8-14 encoding the calmodulin-like domains, with c.1414_1419dupGACGAC emerging as a hotspot variant.Conclusions:COMP-related pseudoachondroplasia and multiple epiphyseal dysplasia predominantly manifest with gait abnormalities and skeletal deformities. COMP gene pathogenic variations were mainly located in calmodulin-like domains.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

Objective To observe the efficacy of positive pressure oxygen therapy combined with drugs to improve pulmonary circulation in the treatment of severe viral pneumonia in high-altitude areas.Methods A two-way cohort study was conducted.Patients with severe viral pneumonia and those with common viral pneumonia complicated with underlying heart and lung diseases admitted to department of intensive care unit of Xizang Autonomous Region People's Hospital were selected as the research subjects.Patients who received conventional treatment in the early stage were assigned to the control group,while those who received conventional treatment plus active positive pressure oxygen therapy combined with drugs to improve pulmonary circulation in the later stage were assigned to the study group.The treatment effective rates of the two groups were observed(including the time for viral nucleic acid to turn negative,hospital stay,and 28-day follow-up mortality)and changes in cardiopulmonary function indicators[pulmonary artery pressure,tricuspid annular plane systolic excursion(TAPSE),left ventricular stroke volume(SV),and lung ultrasounol score(LUS)]before and after treatment were also observed,and the Kaplan-Meier curve was drawn to analyze the 28-day cumulative survival rate of the two groups.Results There was no statistically significant difference in the time for viral nucleic acid to turn negative and hospital stay between the two groups.Compared with the control group,the 28-day mortality in the study group was significantly lower[6.5%(2/31)vs.25.0%(13/52),P<0.05].Compared with before treatment,pulmonary artery pressure gradually decreased,TAPSE significantly increased,and left ventricular SV significantly increased after treatment in the study group,and the differences were statistically significant compared with 10 days after treatment[pulmonary artery pressure(mmHg,1 mmHg≈0.133 kPa):28.84±8.71 vs.34.68±10.76,TAPSE(cm):2.37±0.11 vs.2.03±0.41,SV(mL):68.68±7.17 vs.59.61±6.73,all P<0.01].Pulmonary lesions,especially bilateral pulmonary exudative lesions,significantly improved compared with before treatment,atelectasis improved significantly,and LUS significantly decreased(14.77±5.33 vs.20.32±5.63,P<0.01).Kaplan-Meier curve analysis showed that the 28-day cumulative survival rate in the study group was significantly higher than that in the control group(Log-Rank test:χ2=4.510,P=0.034).Conclusion Active use of positive pressure ventilation and early administration of drugs to improve pulmonary circulation in patients in high-altitude areas can significantly reduce pulmonary artery pressure and significantly improve left and right heart function and pulmonary exudative lesions.These improvements may reduce the mortality rate of viral pneumonia and viral infections complicated with underlying heart and lung diseases in high-altitude areas.