Objective:To investigate the diagnostic value of umbilical cord blood lactic acid and base excess for multi-organ dysfunction following neonatal asphyxia.Methods:A retrospective analysis was conducted on the clinical data of 244 patients at high risk for perinatal asphyxia who received treatment at Dongyang People's Hospital from January 2021 to December 2023.Based on the presence of organ dysfunction, the infants were divided into three groups: a single organ dysfunction group (Group A, n = 55), a multi-organ dysfunction group (Group B, n = 16), and a no organ dysfunction group (Group C, n = 173). Lactic acid levels and base excess values were compared among the three groups. Receiver operating characteristic curves were used to validate the predictive value of lactic acid and base excess values for organ dysfunction. Results:There were no statistically significant differences in general data among the three groups ( P > 0.05). In Group B, the lactic acid level was 15.10 (13.85, 16.83) mmol/L, and the base excess value was 9.80 (6.65, 15.18) mmol/L. In Group A, the lactic acid level was 7.70 (6.25, 11.70) mmol/L, and the base excess value was 5.70 (3.85, 9.60) mmol/L. In Group C, the lactic acid level was 6.80 (4.30, 9.00) mmol/L, and the base excess value was 4.00 (3.00, 6.50) mmol/L. The lactic acid level and base excess value in Group B were significantly higher than those in both Group A and Group C. Additionally, the lactic acid level and base excess value in Group A were significantly greater than those in Group C ( t = 2.60, 20.19, 2.95, 1.92, all P < 0.05). Receiver operating characteristic curve analysis revealed that the combined assessment of base excess value and lactic acid level was more effective than evaluating each parameter individually in predicting the presence of organ damage and multiple organ dysfunction syndrome. Additionally, the detection of base excess value was found to be superior to the measurement of lactic acid level. The areas under the curve values for the combined assessment of base excess value and lactic acid level for the presence of organ damage and multiple organ dysfunction syndrome were 0.694 and 0.856, respectively. In comparison, the AUC values for base excess value detection were 0.678 and 0.846, while the AUC values for lactic acid level measurement were 0.633 and 0.797, respectively. Conclusions:Umbilical cord blood lactic acid and base excess are correlated with organ dysfunction following neonatal asphyxia, and both parameters have clinical value in assessing organ damage.

Objective:To investigate the diagnostic value of umbilical cord blood lactic acid and base excess for multi-organ dysfunction following neonatal asphyxia.Methods:A retrospective analysis was conducted on the clinical data of 244 patients at high risk for perinatal asphyxia who received treatment at Dongyang People's Hospital from January 2021 to December 2023.Based on the presence of organ dysfunction, the infants were divided into three groups: a single organ dysfunction group (Group A, n = 55), a multi-organ dysfunction group (Group B, n = 16), and a no organ dysfunction group (Group C, n = 173). Lactic acid levels and base excess values were compared among the three groups. Receiver operating characteristic curves were used to validate the predictive value of lactic acid and base excess values for organ dysfunction. Results:There were no statistically significant differences in general data among the three groups ( P > 0.05). In Group B, the lactic acid level was 15.10 (13.85, 16.83) mmol/L, and the base excess value was 9.80 (6.65, 15.18) mmol/L. In Group A, the lactic acid level was 7.70 (6.25, 11.70) mmol/L, and the base excess value was 5.70 (3.85, 9.60) mmol/L. In Group C, the lactic acid level was 6.80 (4.30, 9.00) mmol/L, and the base excess value was 4.00 (3.00, 6.50) mmol/L. The lactic acid level and base excess value in Group B were significantly higher than those in both Group A and Group C. Additionally, the lactic acid level and base excess value in Group A were significantly greater than those in Group C ( t = 2.60, 20.19, 2.95, 1.92, all P < 0.05). Receiver operating characteristic curve analysis revealed that the combined assessment of base excess value and lactic acid level was more effective than evaluating each parameter individually in predicting the presence of organ damage and multiple organ dysfunction syndrome. Additionally, the detection of base excess value was found to be superior to the measurement of lactic acid level. The areas under the curve values for the combined assessment of base excess value and lactic acid level for the presence of organ damage and multiple organ dysfunction syndrome were 0.694 and 0.856, respectively. In comparison, the AUC values for base excess value detection were 0.678 and 0.846, while the AUC values for lactic acid level measurement were 0.633 and 0.797, respectively. Conclusions:Umbilical cord blood lactic acid and base excess are correlated with organ dysfunction following neonatal asphyxia, and both parameters have clinical value in assessing organ damage.

Objective: To address the relation among pelvic inflammatory disease (PID), genetic vulnerability and ovarian cancer (OC) risk, we assessed the association between PID and OC risk, alongside the interplay with germline homologous recombination repair (gHR) mutation, utilizing the UK Biobank. Methods: We conducted a prospective cohort study in the UK Biobank by tracking OC incidences between individuals with and without a PID history. Identification of gHR mutations (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1) carriers were accomplished through paired whole-exome sequencing data. We used Cox’s regression models to evaluate the hazard ratios (HRs) for OC risks under PID. Results: In the large prospective cohort study, the adjusted HR for OC in patients with PID was 1.45 (95% confidence interval [CI]=0.90, 2.32) compared with those with non-PID.Intriguingly, age-stratified analysis unveiled a positive association between PID history and OC risk in those aged under 55 years (HR=1.92; 95% CI=1.02, 3.63). Moreover, individuals aged younger than 55 years harboring both a history of PID and gHR mutations exhibited the highest risk of OC (HR=7.40; 95% CI=1.03, 53.10). Conclusion An association between PID and OC risk emerged, notably in the subgroup aged younger than 55 years old. Individuals with both a PID history and gHR mutations exhibited the highest risk of OC. These findings imply PID as a potential precursor for OC, underscoring the importance of early intervention, particularly in the younger population with gHR mutations.

Objective:We applied a hypoxia-induced model of human fetal retinal microvascular endothelial cell (RMEC) to study the effect of carbonic anhydrase 9 (CA9) on cell proliferation.Methods:The eyeballs of spontaneously aborted fetuses in Guangdong Women and Children's Hospital were obtained, and the retinas were isolated. RMEC was obtained by trypsin and collagenase two-step enzyme digestion, and endothelial cells were identified by CD34. The fetal RMEC and the purchased adult RMEC were cultured in normoxic and hypoxic incubators (1%O 2+5%CO 2+94%N 2), and the expression of CA9 was detected by qPCR and Western blot. After knocking down the CA9 by small interference RNA technique, the cell proliferation was detected by CCK-8 method, and the cell viability was detected by CCK-8 after adding CA9 inhibitor U-104. Results:The primary RMEC was extracted successfully. Immunofluorescence staining showed the percentage of CD34 positive cells in the third-generation cells was nearly 100%. The expression of CA9 mRNA in immature fetus and adult RMEC under hypoxia culture was higher than that under normoxic culture (fetal 1% O 2 group vs. fetal 21% O 2 group: 67.80±10.31 vs. 1.00±0.04, P<0.001; adult 1% O 2 group vs. adult 21% O 2 group: 1.72±0.22 vs. 1.00±0.02, P=0.014). Western blot analysis showed significantly increased expression of CA9 in the fetal RMEC exposed to hypoxia, which aligned with the expression of CA9 mRNA. When fetal RMEC was transfected with siCA9 20 nM, the knockdown rate of CA9 was 95% ( P<0.001). CCK-8 assay showed significantly lower proliferation of fetal RMEC cells in siCA9 group compared to siNC group (0.57±0.05 vs. 0.90±0.03, P<0.001), which was reflected by the OD value. With the addition of 100 μM CA9 inhibitor U-104, the viability of fetal RMEC in the treated groupwas significantly lower than that in the untreated group (99.16%±3.82% vs. 119.10% ±1.72%, P=0.002). Conclusions:The expression of CA9 differed between adult and preterm fetus in our hypoxia-induced RMEC model. Inhibiting CA9 can inhibit the proliferation of retinal microvascular endothelial cells of preterm fetus.

ObjectiveTo describe the epidemic characteristics of COVID-19 after policy adjustment from “Category B notifiable disease with category A management” to “Category B notifiable disease with category B management”， and to explore the protective effect of previous infection with SARS-CoV-2 on common symptoms of reinfection. MethodsHealthcare workers infected with SARS-CoV-2 in a grade A tertiary hospital in Shanghai were included in the study from December 4， 2022 to January 11， 2023. Data on demographic characteristics， clinical symptoms， medical history， and COVID-19 vaccination history were collected. We determined the epidemiological curve and characteristics， and then compared the difference in the severity of clinical symptoms between primary and reinfection subjects. ResultsA total of 2 704 cases were included in the study， of which 45 had reinfection， 605 （22.4%）were males， 608 （22.5%）were doctors， 1 275 （47.2%） were nurses， and 2 351 （86.9%） received ≥3 doses of COVID-19 vaccination. The average age of these healthcare workers was （34.9±9.1） years old. The number of cases with mild/moderate illness， asymptomatic infection， fever， headache， dry cough， expectoration， and chest tightness were 2 704 （100.0%）， 92 （3.4%）， 2 385 （88.2%）， 2 066 （76.4%）， 1 642 （60.7%）， 1 807 （66.8%）， and 439 （16.2%）， respectively. Reinfection was a protective factor for fever （OR=0.161， P<0.001）， headache （OR=0.320， P<0.001）， and peak body temperature （β=-0.446， P<0.001）. ConclusionFollowing the COVID-19 policy adjustment as a category B notifiable disease， healthcare workers at a grade A tertiary hospital in Shanghai predominantly experiences mild to moderate COVID-19 symptoms. Reinfection results in milder clinical manifestations， with a lower proportion of being asymptomatic.

Objective: To investigate the seroprevalence and influencing factors of serum neutralizing antibodies among SARS-CoV-2 infected individuals, so as to provide the evidence for developing the health management and COVID-19 vaccination strategy among SARS-CoV-2 infected individuals. Methods: Recovered SARS-CoV-2 infected individuals from January 1st, 2020 to February 10th, 2021 in Zhejiang Province were recruited in March 2021. Participants' demographics, underlying diseases, date of definitive diagnosis and severity of clinical symptoms were collected using questionnaire surveys, and serum neutralizing antibody against SARS-CoV-2 was detected using a fluorescent immunoassay. In addition, factors affecting the seropositivity of neutralizing antibody against SARS-CoV-2 were identified using a multivariable logistic regression model. Results: A total of 559 SARS-CoV-2 infected individuals were enrolled, including 480 confirmed cases and 79 asymptomatic carriers, with an median (interquartile range) age of 47.00 (22.00) years, and all participants had never received COVID-19 vaccination. The median (interquartile range) duration from diagnosis to serum sampling was 387.00 (11.00) days, and the seroprevalence of neutralizing antibody against SARS-CoV-2 was 83.90%. The serum neutralizing antibody against SARS-CoV-2 was all positive 9 months after diagnosis, and the seroprevalence of neutralizing antibody against SARS-CoV-2 appeared no tendency towards a decline with time within 14 months after diagnosis (P>0.05). Multivariable logistic regression analysis showed that women were 1.892 times (95%CI: 1.169-3.064) more likely to produce serum neutralizing antibodies against SARS-CoV-2 than men, and mild, common and severe/critically ill SARS-CoV-2 infected cases were 2.438 (95%CI: 1.305-4.557), 4.481 (95%CI: 2.318-8.663), and 23.525 (95%CI: 2.990-185.068) times more likely to produce serum neutralizing antibodies against SARS-CoV-2 than asymptomatic carrier, respectively. Conclusions The seroprevalence of neutralizing antibody was 100.00% among SARS-CoV-2 infected individuals within 9 months after diagnosis. Individuals' gender and severity of clinical symptoms correlate with the seroprevalence of neutralizing antibody against SARS-CoV-2.

The application of intraocular drug delivery is usually limited due to special anatomical and physiological barriers, and the elimination mechanisms in the eye. Organic nano-drug delivery carriers exhibit excellent adhesion, permeability, targeted modification and controlled release abilities to overcome the obstacles and improve the efficiency of drug delivery and bioavailability. Solid lipid nanoparticles can entrap the active components in the lipid structure to improve the stability of drugs and reduce the production cost. Liposomes can transport hydrophobic or hydrophilic molecules, including small molecules, proteins and nucleic acids. Compared with linear macromolecules, dendrimers have a regular structure and well-defined molecular mass and size, which can precisely control the molecular shape and functional groups. Degradable polymer materials endow nano-delivery systems a variety of size, potential, morphology and other characteristics, which enable controlled release of drugs and are easy to modify with a variety of ligands and functional molecules. Organic biomimetic nanocarriers are highly optimized through evolution of natural particles, showing better biocompatibility and lower toxicity. In this article, we summarize the advantages of organic nanocarriers in overcoming multiple barriers and improving the bioavailability of drugs, and highlight the latest research progresses on the application of organic nanocarriers for treatment of ocular diseases.
Drug Carriers ; Delayed-Action Preparations ; Drug Delivery Systems ; Nanoparticles/chemistry*

Objective : To analyze the epidemiological characteristics and pathogen spectrum of hand，foot mouth disease (HFMD) in Anhui province from 2015 to 2022，and to provide scientific evidence for prevention and control measures of HFMD． Methods : The surveillance data of hand，foot and mouth disease in Anhui province from 2015 to 2022 were analyzed by descriptive epidemiology. Real-time PCR was used to detect and classify HFMD samples. Results : A total of 650 590 HFMD cases were reported in Anhui province from 2015 to 2022，including 1 406 se- vere cases and 17 deaths．The annual reported incidence was 131. 45 /100 000．The epidemic features of“low incidence in odd years and high incidence in even years”were presented from 2015 to 2019．The incidence showed a continuous decline from 2020 to 2022．The monthly distribution showed the characteristics of bimodal epidemic，and the main peak was not obvious in 2020．Hefei，Fuyang，Bozhou，Chuzhou and Suzhou ranked the top five cities in terms of cumulative incidence．The age of onset was mainly distributed in children aged 5 years and below，accounting for 89. 26% of the total cases．The male to female ratio was 1. 48 ∶ 1．A total of 28 657 laboratory-confirmed cases had been reported from 2015 to 2022．EV71 cases accounted for 10. 57% ，Cox A16 cases accounted for 24. 90% ，and other enterovirus cases accounted for 64. 53%．The dominant pathogens showed dynamic changes in different years．Since 2018，the proportion of EV71 decreased significantly，and the proportion of other enteroviruses gradually increased to become the dominant pathogens．Among other enteroviruses，Cox A6 strain was dominant (80. 48% ) ． Conclusion This study suggests that the prevention and control of HFMD in Anhui province should be paid more attention from April to July and from October to December．The focus areas are the cities in northern Anhui and Hefei where the floating population is large．The focus of prevention and control is on children aged 5 years and below．Other enteroviruses have become the dominant pathogens of hand-foot-mouth disease in Anhui province，Cox A6 strain is dominant.

Finding stable expression sites on the chromosomes of Chinese hamster ovary (CHO) cells is an effective method to solve the problem of unstable expression of CHO cells in long-term culture. Our group used lentiviral transfection to integrate the tracer gene (Zsgreen1) into the chromosome of CHO cells and found multiple potential stable expression sites. This study verified the ability of one of the sites located in the 148052-148157 bp region on chromosome NW_003614241.1 to stably express exogenous proteins.The expression of Zsgreen1 gene was first observed, and CRISPR/Cas9 technology was then used to integrate the enhanced green fluorescent protein (EGFP) gene into this site. Three strains of EGFP gene integrated cells were obtained. After 60 generations of suspension culture, the fluorescence intensity of the cells had no significant changes, which proved that this site can stably express the EGFP gene. The same method was used to construct recombinant CHO cell lines expressing the human serum albumin (HSA) gene, and was verified by Western blot that this site could express and secrete HSA. It shows that the above-mentioned sites can be integrated and can stably express exogenous proteins.

Objective:To establish an analytical method for the simultaneous determination of five fat-soluble vitamins in serum using isotope dilution ultra high performance liquid chromatography-tandem mass spectrometry (ID-UPLC-MSMS).Methods:Fat-soluble vitamins were obtained from serum samples which collected from Shanghai Tenth People′s Hospital between April 2019 and August 2019 by the extraction method, and were detected by ID-UPLC-MSMS. The performance of the method was verified by referring to the relevant documents of the Clinical and Laboratory Standards Institute (CLSI).Results:The ID-UPLC-MSMS method for the rapid detection of various fat-soluble vitamins in serum was proposed and successfully verified. The linear range of the method: vitamin A: 25-2 500 μg/L, 25(OH)D 2: 2-200 μg/L, 25(OH)D 3: 2-200 μg/L, vitamin E: 0.25-50 mg/L, vitamin K1: 0.1-20 μg/L. The intra- and inter-assay precision standard deviations of the five analytes were within ± 15%, and the accuracy of the test results of the 25(OH)D 2 and 25(OH)D 3 standards was 96.44%-102.37%. Conclusion:The performance of ID-UPLC-MSMS method for the simultaneous determination of five fat-soluble vitamins is satisying, and the result is accurate and reliable, which suggested it can be used for the clinical sample.