ObjectiveTo observe ovarian microvascular damage in rats with cold coagulation and blood stasis syndrome and to explore the mechanism by which Liangfang Wenjing decoction improves this condition in rats. MethodsFifty SPF female SD rats were randomly divided into a blank group， a model group， low-dose （8.1 g·kg^-1） and high-dose groups （16.2 g·kg^-1） of Liangfang Wenjing decoction， and a 4-phenylbutyric acid （0.1 g·kg^-1） group， with 10 rats in each group. The ice-water bath method was employed to establish the rat model of cold coagulation and blood stasis syndrome. Concurrent with modeling， Liangfang Wenjing decoction was administered continuously for 21 days， once daily. The rats' syndrome manifestations and estrous cycles were recorded. The enzyme-linked immunosorbent assay （ELISA） was used to detect serum reproductive hormone levels and levels of endothelin-1 （ET-1）， nitric oxide （NO）， thrombomodulin （TM）， and von Willebrand factor （vWF） in ovarian tissue. Prothrombin time （PT）， activated partial thromboplastin time （APTT）， thrombin time （TT）， and fibrinogen （FIB） were measured. The ovarian microcirculatory blood perfusion was detected by laser speckle contrast imaging. Hematoxylin-eosin （HE） staining was performed to observe the ovarian histopathology， flow cytometry to detect ovarian apoptosis rate， and transmission electron microscopy to observe the ultrastructure of ovarian microvascular endothelial cells. Western blot was employed to detect the protein expression of endothelial nitric oxide synthase （eNOS）， phosphorylated eNOS （p-eNOS）， Caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， inositol-requiring enzyme1α （IRE1α）， p-IRE1α， apoptosis signal-regulating kinase 1 （ASK1）， p-ASK1， c-Jun N-terminal kinase （JNK）， and p-JNK. Immunofluorescence was used to detect ovarian Bax and Bcl-2 expression in microvascular endothelial cells. ResultsCompared with the blank group， the model group showed signs of cold coagulation and blood stasis syndrome， prolonged estrus cycles， and reproductive hormone disorders. Histopathological results revealed a decrease in follicle counts at all stages and disorganized granulosa cell arrangement. Ovarian microcirculatory perfusion was significantly decreased （P<0.01）. PT， APTT， and TT were reduced （P<0.05， P<0.01）， while FIB levels were increased （P<0.05）. In ovarian tissue， NO content was decreased， while ET-1， vWF， and TM levels were increased significantly （P<0.01）. The apoptosis rate of ovarian cells was markedly increased （P<0.01）. Furthermore， p-eNOS/eNOS and Bcl-2 were decreased （P<0.05）， whereas Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK expression showed significant increases （P<0.05， P<0.01）. Compared with the model group， Liangfang Wenjing decoction intervention alleviated the symptoms of cold coagulation and blood stasis， gradually restored the estrus cycle， and improved ovarian histopathology and endothelial cell ultrastructure. Microcirculatory blood perfusion was significantly elevated （P<0.05）. NO content in ovarian tissue was elevated， while ET-1， vWF， and TM levels were significantly decreased （P<0.05， P<0.01）. The p-eNOS/eNOS ratio and Bcl-2 expression were significantly elevated （P<0.05）， while the expression of Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK was significantly decreased （P<0.05， P<0.01）. ConclusionLiangfang Wenjing decoction may regulate the IRE1α/ASK1/JNK signaling pathway to inhibit endoplasmic reticulum stress， attenuate apoptosis， and improve microvascular endothelial injury in ovaries of rats with cold coagulation and blood stasis syndrome.

Objective To observe the clinical efficacy of"three modulation acupuncture"combined with repeated functional magnetic stimulation(rFMS)in the treatment of neurogenic bladder with detrusor muscle weakness after spinal cord injury.Methods A total of 120 patients with neurogenic bladder with detrusor muscle weakness after spinal cord injury were divided into conventional treatment group,"three modulation acupuncture"treatment group,rFMS treatment group and comprehensive treatment group according to the random number table method,with 30 patients per group.The conventional treatment group was given conventional rehabilitation treatment,the"three modulation acupuncture"treatment group was treated with"three modulation acupuncture"(modulating spirit,modulating reflex arc,and modulating lower jiao and waterway)based on conventional rehabilitation treatment,the rFMS treatment group was treated with rFMS based on conventional rehabilitation treatment,and the comprehensive treatment group was treated with"three modulation acupuncture"and rFMS based on conventional rehabilitation treatment.The first desire to void(FDV),maximum cystometric capacity(MCC),maximum detrusor pressure of urine storage period(Pdet.max),maximum intravesical pressure of urine storage period(Pves.max),average daily urination frequency,average daily urine leakage,residual urine volume,and neurogenic bladder symptom scores of the patients were compared before and after treatment,and the clinical effectiveness of each group was evaluated.Results After treatment,the FDV,MCC,and Pdet.max of the four groups were all increased compared with those before treatment,and Pves.max,the average daily urination frequency,the average daily frequency of urine leakage,the residual urine volume,and the neurogenic bladder symptom scores were all decreased(P<0.05).After treatment,the FDV,MCC,and Pdet.max of the"three modulation acupuncture"treatment group,the rFMS treatment group and the comprehensive treatment group were all higher than those of the conventional treatment group,and Pves.max,the average daily urination frequency,the average daily frequency of urine leakage,the residual urine volume,and the neurogenic bladder symptom scores were all lower(P<0.05).After treatment,the comprehensive treatment group had a higher FDV,MCC,and Pdet.max than the"three modulation acupuncture"treatment group and rFMS treatment group,and Pves.max,the average daily urination frequency,the average daily frequency of urine leakage,the residual urine volume,and the neurogenic bladder symptom scores were lower(P<0.05).The curative efficiency rates were 86.2%(25/29)in the"three modulation acupuncture"treatment group,85.7%(24/28)in the rFMS treatment group,and 92.6%(25/27)in the comprehensive treatment group,which was higher than that of the conventional treatment group,which was 75.9%(22/29).Conclusion"Three modulation acupuncture"and rFMS can effectively improve the functional status of the bladder in patients of neurogenic bladder with detrusor muscle weakness after spinal cord injury,and their combined application has a synergistic effect.

To analyze the trends in disease burden and risk factors of depression among the elderly population in China from 1990 to 2021, and to provide a theoretical basis for the prevention, treatment, and policy-making of geriatric depression in China.

Objective:To study the clinical features, genetic characteristics and prognosis of neonatal diabetes mellitus (NDM).Methods:From January 2015 to January 2022, neonates with NDM admitted to the Department of Neonatology of our hospital were retrospectively reviewed.Their clinical manifestations, biochemical data, genetic tests, treatments and outcomes were analyzed.Results:A total of 6 cases with NDM were included, with 3 males and 3 females. All 6 cases were full-term infants, 5 were low birth weight infants and 1 had family history of diabetes. High blood glucose were found on 1~11 d (average 4 d) after birth. 3 cases were diagnosed during blood glucose screening for low birth weight and 3 cases were diagnosed due to infection and/or diabetic ketoacidosis. Blood C-peptide levels were below normal range in all 6 cases. Blood insulin levels were decreased in 5 cases and remained at the lower limit of normal range in 1 case. All infants received genetic tests and 4 showed abnormal results, including 2 cases of ABCC8 gene mutation [c.2060C>T (p.T687M), not reported; c.674T>C (p.L225P), reported], 1 case of KCNJ11 gene mutation [c.602G>A (p.Arg201His), not reported] and 1 case of paternal uniparental disomy (UPD)6q24 (reported). All 6 cases were treated with insulin. Glibenclamide was experimented to replace insulin in 3 cases and 1 case was successful. During follow-up (at the age 4 months~5 years old), 4 cases were diagnosed with transient NDM, 1 case with permanent NDM and 1 case died at the age of 4 months without classification. 1 case showed psychomotor and language delay and the others had otherwise normal development.Conclusions:Most NDM infants are low birth weight infants with reduced blood insulin and C-peptide.Transient NDM are common. Proactive genetic testing may help treatment.

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa+Nppb+Ankrd1+cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after Ml.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.
Humans ; Fusobacterium nucleatum/metabolism* ; NF-kappa B/metabolism* ; Periodontal Ligament/metabolism* ; Signal Transduction ; Fusobacterium Infections/pathology* ; Stem Cells/metabolism*

Objective: To analyze the epidemiological characteristics of infectious diseases at schools in Beijing from 2010 to 2020, providing evidence for the prevention and control strategies in school infectious diseases. Methods: Information on public health emergencies was collected from Public Health Emergency Reporting System (the subsystem of Chinese Disease Prevention and Control Information System) reported from 2010 to 2020. Results: A total of 146 public health emergencies and 138 public health emergencies of infectious diseases in schools were reported in Beijing from 2010 to 2020, including 4 291 cases with the rate of 2.32% and affected or exposed 185 179 cases. There were significant difference in mean annual incidence rates( χ 2=782.46, P <0.01). There were 71 events of respiratory infectious diseases and 66 events of intestinal infectious diseases, accounting for 51.45% and 47.83%, respectively. The annual incidence peaks of public health emergencies of infectious diseases were during March-June and October-December. The events mainly occurred in kindergartens and primary schools among each stage of school periods with 51 and 46 incidences respectively, which accounted for 70.29% of the total number of public health emergencies in schools. The leading infectious diseases among all the reported events in kindergartens and primary schools were hand foot mouth disease and varicella. Varicella and other infectious diarrhoeal diseases were at the top lists of infectious disease outbreaks at the secondary and university stages. Conclusion Infectious diseases events were the major type of public health emergencies at schools in Beijing from 2010 to 2020. Respiratory infectious diseases and intestinal infectious diseases were the keys to the prevention and control of public health emergencies related to school. It is necessary to strengthen the surveillance for public health emergencies especially for symptom surveillance. The prevention and control measures should be taken according to the characteristics of different age groups. At the same time, the prevention and control of school infectious diseases and the drill of the plan during peak periods need to be particularly strengthened.

Objective:To build a competency index system for "double-qualified" nursing teachers in application-oriented universities.Methods:The overall research period was from September 2020 to February 2021. The literature research and behavioral event interview were used to initially form the competency index system for "double-qualified" nursing teachers in application-oriented universities. A total of 20 nursing experts from Qiqihar Medical University and its three affiliated hospitals were selected by convenience sampling. Delphi expert consultation was used to conduct two rounds of consultations.Results:Among two rounds of consultations, the effective response rates of the questionnaires were all 100%, and the expert authority coefficients were 0.815 and 0.845, and the Kendall harmony coefficients were 0.236 and 0.243, respectively. The final form of the competency index system for "double-qualified" nursing teachers in application-oriented universities included 5 dimensions and 23 items.Conclusions:The competency index system for "double-qualified" nursing teachers in application-oriented universities has clear indicators, which can be used as a quantitative reference basis for university and hospital education, and manager training, assessment as well as evaluation of nursing teachers.

Objective:To study the impact of preoperative serum HBV DNA levels on prognosis of hepatocellular carcinoma (HCC) patients undergoing hepatectomy with curative intent.Methods:The clinical data of patients with HCC treated by hepatectomy with curative intent at the Guangxi Medical University Cancer Hospital from January 2010 to December 2016 were retrospectively analyzed. According to the preoperative serum HBV DNA levels, patients were divided into three groups: the control group (HBV DNA negative), the low load group (<10 4 copy/ml) and the high load group (≥10 4 copy/ml). The clinical data of these patients were collected and long-term survival outcomes of these patients were followed-up. The Kaplan-Meier method was used to compare the overall survival (OS) and recurrence-free survival (RFS) rates among the three groups. Using the Barcelona clinic liver cancer classification (BCLC), patients with different serum HBV DNA levels were further divided into three subgroups: stage 0/A, stage B and stage C. The OS and RFS rates of patients in each of these subgroups were compared. Results:Of 1 180 patients who were enrolled in the study, there were 1 024 males and 156 females, aged (48.6±10.8) years. The 1-, 3- and 5-year OS rates for patients in the control group ( n=258) were 91.5%, 79.3% and 74.9%, respectively; while those in the low load group ( n=289) were 87.2%, 68.6% and 61.6%, respectively; and those in the high load group ( n=633) were 85.4%, 68.9% and 60.7%, respectively. The 1-, 3- and 5-year OS rates in the control group were significantly better than those in the low load group and the high load group ( P<0.05). The 1-, 2- and 3-year RFS rates in the control group were significantly higher than those in the high load group ( P<0.05). Subgroup analysis showed that in the BCLC 0/A subgroup ( n=786) the 1-, 3- and 5-year OS rates in the control group were significantly better than those in the high load group ( P<0.05). In the BCLC B subgroup ( n=181), the 1-, 2- and 3-year RFS rates in the control group were significantly higher than those in the high load group ( P<0.05). In the BCLC C subgroup ( n=214), there were no significant differences in the 1-, 3- and 5-year OS and 1-, 2- and 3-year RFS rates among the three groups ( P>0.05). Conclusion:For HCC patients undergoing hepatectomy with curative intent, the higher the preoperative serum HBV-DNA level, the worse the long-term survival outcomes.

The importance of gut microbes to human health has gradually attracted attention. With the use of animal models, it has been revealed that maternal microbes during pregnancy could influence their children's health outcomes through shaping their microbial composition and regulating the development of their metabolic and immune system. However, the physiological mechanism of the human body is more complex and is affected by the interaction of multiple factors. The research results obtained from animal models are often inconsistent with human studies. At present, the influence of maternal intestinal microbes during pregnancy on the microbial colonization in their offspring and on a series of children's health outcomes is still unclear. Establishing a sub-cohort to detect the microbiome of the women across pregnancy and of their offspring, and further to integrate with variety of environmental and behavioral exposures can better provide reliable support for the research on the mechanism of children's health and diseases. This paper briefly introduces the research objectives, content, progress, strength and limitations of the sub-cohort study.