ObjectiveTo analyze the pharmacodynamic substance basis of Shangkeling Spray and its potential mechanisms in intervening knee osteoarthritis （KOA） using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS）， network pharmacology， and molecular docking technology. MethodsUPLC-MS was used to identify the chemical components of Shangkeling Spray. Pharmacokinetic properties were employed to screen potential active ingredients. Network pharmacology methods were utilized to collect potential targets of these ingredients and the pathological gene set of KOA. An "active ingredient-disease" target network was constructed using databases such as STRING. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） functional enrichment analyses were performed using clusterProfiler. Libraries including NumPy were employed to calculate shortest path lengths to identify dominant pharmacodynamic links. Core gene clusters were identified using MCODE， validated through the Gene Expression Omnibus （GEO） database， and molecular docking was performed between key active ingredients and core targets. ResultsA total of 322 and 314 chemical components were identified under positive and negative ion modes， respectively， with 410 components in total after de-duplication， mainly including flavonoids， coumarins， terpenoids， organic acids， and alkaloids. Analysis of the "active ingredient-disease" network identified "development and regeneration"， "cell growth and death"， "immune system"， and "nervous system" as the dominant pharmacodynamic links of Shangkeling Spray in the treatment of KOA. Molecular docking showed that key active ingredients， such as bletillin A， formononetin， morin， oxymatrine， aconitine， gallic acid， curdione， apigenin， naringenin， and oleanolic acid， tightly bound to functional domains of 10 key targets including Jun proteins（JUN）， interleukin-6 （IL-6）， protein kinase B1 （Akt1）， Caspase-3， nuclear transcription factor-κB subunit p65（RELA）， nuclear factor-kappaB1（NF-κB1）， Cyclin D₁， mammalian target of rapamycin（mTOR）， tumor necrosis factor （TNF）， and Fos proto-oncogene protein （FOS）. These interactions synergistically regulated the phosphatidylinositol 3-kinase （PI3K）/Akt/mTOR-related signaling axis and nervous system-related pathways， mediating cartilage repair， reducing inflammation and pain， and improving KOA. ConclusionThis study preliminarily clarifies the pharmacodynamic substance basis of Shangkeling Spray and suggests that its main active ingredients may improve KOA by synergistically regulating the PI3K/Akt/mTOR-related pathways， providing a reference for subsequent exploration of its substance benchmark and mechanism of action.

Objective: To monitor the prevelance of Neisseria meningitidis among healthy children and adolescents aged 3-18 in Anhui Province, so as to provide support for epidemic cerebrospinal meningitis prevention and control. Methods: From September to October in 2021 and 2022, 4 033 healthy children and adolescents aged 3-18 were selected by stratified random sampling from Anhui Province, including areas north of the Yangtze River (Bozhou, Fuyang, Bengbu, Huainan, Chuzhou, Hefei) and areas south of the Yangtze River (Wuhu, Maanshan, Tongling, Anqing, Chizhou, Xuancheng) and the secretions of children and adolescents were collected from the posterior pharyngeal wall above the uvula, and the strains were identified by bacterial culture and nucleic acid detection. McNemar test and Kappa consistency test were used for statistical analysis. Chisquare test and Chisquare trend test were used to compare the rates. Results: The carrier rates of Neisseria meningitidis were 0.47% and 1.07%, respectively. The sensitivity of nucleic acid detection was higher. Among the detected bacteria, group B accounted for the largest proportion of 76.74%. It was followed by group C (4.65%), group Y (4.65%), group W 135 (2.33%) and group X (2.33%). The bacteria bearing rate of male students was higher than that of female students (χ2=11.44); with the increase of age, the bacteria bearing rate of children and adolescents showed an increasing trend (χ2trend=42.69); the bacterial bearing rate of children and adolescents in the north of the Yangtze River was higher than that in the south of the Yangtze River (χ2=23.19); the bacteria bearing rate of children and adolescents without immune history was higher than that with immune history (χ2=11.02)(P<0.01). Conclusions Neisseria meningitidis group B has become an epidemic strain in Anhui Province, and senior children and adolescents have become the key population of epidemic prevention and control. It is necessary to continue to do a good job in the surveillance of epidemic cerebrospinal meningitis disease and focuse on group B disease cases, so as to prevent the occurrence of cluster outbreaks in schools.

OBJECTIVE To study the protective effect and possible mechanism of soybean isoflavones against threatened miscarriage rats. METHODS Female mice were selected to promote estrus and mate with male mice. After pregnancy， they were randomly divided into normal group （purified water， i.g.， n＝10）， model group （purified water， i.g.， n＝9）， positive control drug group （progesterone 4 mg/kg， i.m.， n＝9）， low-， medium- and high-dose soybean isoflavone groups （25， 50 and 100 mg/kg， i.g.， n＝10）. Except for the normal group， the rest were given mifepristone+misoprostol on the 8th day of pregnancy to establish threatened miscarriage model， and then given purified water or drugs， once a day， on days 1-7 and 9-12 of pregnancy， respectively. At 14 days of pregnancy， the rates of fetal protection were counted. Serum levels of β-human chorionic gonadotrophin （β-HCG） and progesterone （P） in rats were detected. Pathological and morphological changes in rat placenta and decidua tissues were observed， and the apoptosis indexes of cells were detected； mRNA and protein expressions of factor of apoptosis related （Fas）， factor of apoptosis related ligand （FasL）， proliferating cell nuclear antigen （PCNA） and heparin binding epidermal growth factor （HB-EGF） were determined in placenta tissues， and mRNA and protein expressions of Fas， PCNA and HB-EGF in decidua tissues were detected. RESULTS In the model group， the placental tissues of rats were hyperemia and dilatation， with fewer and irregular blood vessels； severe stromal edema，inflammatory cell infiltration and iron-choledrin depositionwere observed. Compared with model group， the fetal survival rates， serum levels of β-HCG and P， the expressions of PCNA and HB-EGF mRNA and proteins in the placenta and decidua tissue of soybean isoflavone groups increased significantly （P＜ 0.05）， while pathological changes were improved significantly； cell apoptosis index in the placenta and decidua tissue， the expressions of Fas， FasL mRNA and proteins in the placenta and Fas mRNA and protein in the decidua tissue decreased significantly （P＜0.05）. The effect of soybean isoflavones was dose-dependent （P＜0.05）. CONCLUSIONS Soybean isoflavone has protective effect on threatened miscarriage， the mechanism of which is related to down-regulating the expressions of Fas and FasL mRNA and protein at the maternal-fetal interface， and up-regulating the expressions of mRNA and protein of PCNA and HB- EGF.

Objective To explore the impact of the sialic acid binding lectin-E(Siglec-E)on the inhibitory properties of parthenolide(PTL)against lipopolysaccharide(LPS)-induced M1 polarization of microglia(BV2).Methods ①Single cell sequencing data of Siglece related mouse brain tissue was obtained from Gene Expression Omnibus(GEO)database and divided into the WT group(n=3)and the Siglece-/-group(n=4).The microglia cells were screened,and the enrichment analysis was performed to analyze related differential genes and pathways.BV2 cells were constructed by the shRNA interference technique and were divided into NC-shRNA and Siglece-shRNA to detect the expression level of Siglec-E(Siglece).② NC-shRNA and Siglece-shRNA cells were respectively divided into the Control group,LPS group,PTL group and PTL+LPS group(n=3).The mRNA levels of markers of M1 polarization in microglia,iNOS,IL-1 β and IL-6,were detected by RT-qPCR.Siglecefl/fl and Cx3cr1cre mice were mated to obtain microglia-specific Siglece deletion(Siglecefl/fl×Cx3cr1cre)mice,and LPS-induced neuroinflammation model was established.③ Nine WT and Siglecefl/fl×Cx3cr1cre male mice were assigned to the Control group,LPS group and PTL+LPS group(n=3).RT-qPCR,immunofluorescence assay and Western blotting were used to verify the knock-out effect and polarization-related pathways,and to investigate the mechanism of Siglec-E affecting PTL inhibition of M1 polarization of microglia.Results Compared with the NC-shRNA group,the expression of Siglec-E in the Siglece-shRNA group was significantly decreased(P<0.01),indicating that the Siglec-E knock-down cell model was successfully established.With the stimulation of LPS,mRNA levels ofiNOS,IL-1 β and IL-6 were significantly up-regulated compared with the Control group both in shRNA cells and Siglece-shRNA cells(P<0.01).With the influence of PTL and LPS,the markers of M1 polarization in NC-shRNA cells mentioned before were significantly decreased(P<0.05),while for Siglice-shRNA cells,there were no significant changes in the markers of M1 polarization.PTL inhibited the phosphorylation of JNK and IκB protein(P<0.01)and the nuclear translocation of NF-κB in BV2 cells,down-regulated Siglec-E,and weakened the inhibitory effect.Compared with mice in the WT group,the expression of Siglec-E in microglia of Siglecefl/fl×Cx3cr1cre mice was decreased significantly(P<0.01),and the inhibitory effect of PTL on the phosphorylation of NF-κB in microglia of Siglecefl/fl×Cx3cr1cre mice was also decreased.Conclusion The absence of Siglec-E in microglia attenuates the inhibition of M1 polarization by the MAPK/NF-κB pathway targeted by PTL.

Objective:To establish an environmental management strategy for the prevention of ventilator-associated pneumonia from the perspective of etiological characteristics and to verify its application effect.Methods:Based on a sampling survey, this study constructed preventive management strategies for ventilator-associated pneumonia by blocking pathogen characteristics from the perspective of both colonization and infection management in patients. From July 2021 to June 2023, a non-synchronous randomized controlled study was conducted, including a control group of 59 cases and an experimental group of 57 cases from ICU of Tianjin Teda Hospital, all of them were mechanically ventilated patients. The effectiveness of the strategy was confirmed.Results:In the control group, there were 35 males and 24 females, with an average age of (46.97 ± 18.84) years. In the experimental group, there were 39 males and 18 females, with an average age of (47.49 ± 13.85) years. During the study period, there were 9 cases of ventilator-associated pneumonia (VAP) in the control group and 2 cases in the experimental group, the difference between the two groups was statistically significant (exact odds ratio=0.031). The duration of mechanical ventilation in the experimental group (122.41 ± 18.36) h, which was shorter than that in the control group (187.62 ± 18.05) h, and the difference was statistically significant ( t=19.28, P<0.05). The length of ICU stay in the experimental group was (8.38 ± 0.79) d, in the control group was (10.99 ± 1.10) d, the difference between them was statistically significant ( t=14.66, P<0.05). On the 7th day, there were 7 cases of positive pathogenic bacteria in sputum culture in the experimental group, which was significantly different from the 29 cases in the control group ( χ2=16.73, P<0.05). Conclusions:The vector management strategy for preventing ventilator-associated pneumonia by blocking etiological characteristics can reduce the incidence of VAP, shorten the duration of mechanical ventilation and ICU stay, and reduce the pathogen load in the sputum of mechanically ventilated patients on the 7th day.

Background and Aims:In recent years,function-preserving proximal gastrectomy with reconstruction has become an important approach for the treatment of early gastric cancer.However,there is no standardized surgical technique,and the short-and long-term outcomes of various new procedures remain unclear.This study was performed to evaluate the safety and short-term efficacy of laparoscopic proximal gastrectomy plus esophagogastrostomy with single-flap technique for early gastric cancer. Methods:The clinical data and follow-up records of 7 patients who underwent laparoscopic proximal gastrectomy with single-flap esophagogastrostomy in the First Affiliated Hospital of Soochow University between December 2021 and December 2022 were retrospectively analyzed.Perioperative safety,postoperative reflux,anastomotic stricture at 6 months,and related nutritional parameters were assessed.The nutrition-related indicators of this group of patients were compared with those of 11 patients who underwent total gastrectomy with Roux-en-Y anastomosis for early gastric cancer during the same period. Results:All 7 patients successfully underwent laparoscopic proximal gastrectomy with single-flap esophagogastrostomy.The average operative time was(212.9±20.6)min,with anastomosis taking(54.7±10.5)min;the mean intraoperative blood loss was(28.6±9.0)mL.No Clavien-Dindo grade Ⅲ or higher complications were observed during hospitalization.None of the patients experienced significant reflux symptoms,although 1 patient developed anastomotic stricture 3 months after operation.There were no statistically significant differences in hemoglobin concentration,albumin level,prealbumin level,total protein concentration,and lymphocyte count between preoperative and 6-month postoperative measurements(all P＞0.05).Compared to patients who underwent total gastrectomy with Roux-en-Y anastomosis,those who had the proximal gastrectomy with single-flap esophagogastrostomy showed a lower percentage decrease in body weight,skeletal muscle area at the third lumbar vertebra(L3),visceral fat area at L3,and hemoglobin concentration at 1 year after operation(all P＜0.05). Conclusion:Laparoscopic proximal gastrectomy with single-flap esophagogastrostomy is a safe and feasible surgical option for early gastric cancer,offering effective anti-reflux outcomes while minimizing the risk of anastomotic stricture.This procedure has a lower impact on postoperative nutritional status compared to total gastrectomy.

Objective:To explore the produced-radiation brain damage in simulated solar particle events and to provide evidence for health risk assessment of radiation from manned deep space exploration.Methods:According to the main characteristics of solar particle events, mice were treated with total body irradiation (TBI) with 90 MeV protons in a dose range from 0.1 to 2 Gy, with irradiation dose of 0, 0.1, 0.3, 0.5, 1, 2 Gy, respectively. At 3 and 7 d after irradiation, the behavior of mice was examined using balance beam tests, rotarod tests, and new object recognition tests. Then, the density of dendritic spines and the number of Nissl bodies in the hippocampus were measured using Golgi and Nissl staining. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and neurotransmitter content in brain tissue were detected using the WST-8 method, TBA method, and high pressure liquid chromatography (HPLC), respectively. Besides, cell apoptosis was determined using the TUNEL method, and the dose-response relationship, a function of dose change with damage index, was analyzed using linear and linear square fitting method. Finally, the minimum radiation dose causing a significant change in all indicators of brain damage was determined as the brain damage threshold.Results:Compared to the control group, 1 Gy proton irradiation result ed in a significant decrease in the density of filopod dendritic spines ( t = 1.82, 2.30, P < 0.05) and a significant increase in abnormal Nissl bodies in the CA1 region ( t = 2.44, 3.77, P < 0.05). At 3 and 7 d after irradiation, as well as a significant increase in the DA ( t = 2.52, P<0.05) and Glu contents ( t = 4.04, P < 0.05) on day 7. In contrast, 2 Gy proton irradiation result ed in a decrease in SOD activity on day 3 ( t = 3.44, P < 0.05), and an increase in the MDA content ( t = 1.90, 2.14, P < 0.05), hippocampal cell apoptosis (t = 3.91, 3.54, P < 0.05), and 5-HT levels ( t = 2.81, 2.69, P < 0.05), together with a decrease in climbing time in the rotarod tests ( t = 2.85, 2.64, P<0.05) and propensity to recognize new objects ( t = 2.87, 2.84, P < 0.05) on days 3 and 7. Furthermore, a dose-response relationship was observed in the dose range from 0.1 to 2 Gy ( R2=0.74-0.99). Conclusions:The dose threshold of 90 MeV protons inducing brain damage in mice is inferred to be 1 Gy, and 14 dose-response models are developed, providing a biological basis for organ dose capping and risk assessment of crew experiencing short-term deep space flights.

Objective:To investigate the effect of prenatal dexamethasone on short-term outcomes and long-term neurological development in late preterm infants with twin pregnancy.Methods:A total of 315 pregnant women with twin pregnancy and their preterm infants who delivered in Peking University Third Hospital from January 2019 to December 2022 were retrospectively analyzed. The clinical data of pregnant women and preterm infants were collected. They were divided into non-medication group (93 pregnant women and 186 preterm infants), medication after 34 weeks group (123 pregnant women and 246 preterm infants), and medication before 34 weeks group (99 pregnant women and 198 preterm infants). Short-term outcomes of preterm infants were analyzed, including the incidence of neonatal respiratory distress syndrome (NRDS), wet lung, hypoglycemia, neonatal septicemia, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD) and neonatal necrotizing enterocolitis (NEC). "Ages and Stages Questionnaire-Third Edition (ASQ-3) scale" was used to follow up the late neurological development of preterm infants at the corrected age of 6-54 months, and the level of neurological development was compared.Results:(1) General conditions: the gestational age at delivery in the non-medication group [36.1 weeks (35.6, 36.6 weeks)] was later than that in the medication after 34 weeks group [36.1 weeks (35.2, 36.4 weeks)] and medication before 34 weeks group [35.2 weeks (34.2, 36.2 weeks)] groups, and the differences were statistically significant (all P<0.05). After correcting for gestational age, there was no significant difference in birth weight among the three groups ( H=3.808, P=0.149). There were no significant differences in gender and the proportion of small for gestational age among the three groups (all P>0.05). (2) Short-term outcome: the incidence of wet lung was 7.0% (13/186), 11.0% (27/246) and 16.2% (32/198) in the non-medication group, medication after 34 weeks group and medication before 34 weeks group, respectively, and the difference was statistically significant ( P=0.018). There were no significant differences in the incidence rates of NRDS, hypoglycemia, sepsis, IVH, BPD, and NEC among the three groups (all P>0.05). Logistic regression analysis with gestational age and newborn birth weight as confounding factors showed that early gestational age ( OR=0.884, 95% CI: 0.837-0.933, P<0.001) and increased incidence of selective intrauterine growth restriction type I ( OR=2.967, 95% CI: 1.153-7.639, P=0.024) could both lead to an increased incidence of wet lung. (3) Long-term outcomes: a total of 109 pregnant women completed the follow-up, and 218 preterm infants with a corrected age of 6-54 months at the end of follow-up were enrolled, including 86 cases in the non-medication group, 66 cases in the medication after 34 weeks group, and 66 cases in the medication before 34 weeks group. There were no significant differences in the scores of communication, gross motor, fine motor, problem solving and personal-social among the three groups (all P>0.05). Conclusion:Prenatal administration of a single course of dexamethasone does not affect the neonatal birth weight and short-term outcomes of twin late preterm infants, and has no adverse effect on the neurological development of twin late preterm infants with a corrected age of 6-54 months.

Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,stress reduction,and social behaviors.In rodents,grooming involves a patterned and sequenced structure,known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style,beginning from the nose to the face,to the head,and finally ending with body licking.The context-dependent occurrence of grooming behavior indicates its adaptive significance.This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes.We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models,holding promise for translational psychiatry.Herein,we mainly focus on rodent self-grooming.Allogrooming(grooming being applied on one animal by its conspecifics via licking or carefully nibbling)and heterogrooming(a form of grooming behavior directing towards another animal,which occurs in other contexts,such as maternal,sexual,aggressive,or social behaviors)are not covered due to space constraints.

Objective To explore the effect of bone marrow injury by simulating the radiation from solar particle events in order to address the radiation limit and assess risks during manned deep space exploration.Methods In line with solar particle events(the main component was protons),BALB/c mice(48 mice per group)were irradiated with 90 MeV protons at the doses of 0,0.1,0.3,0.5,1 and 2 Gy.At 3 and 7 days after irradiation.Routine blood counters were employed to detect peripheral blood changes,Giemsa staining was used to detect the ratio of granulocytes to erythrocytes in bone marrow,and flow cytometry was adopted to detect the proportion of bone marrow stem cells,cell subsets and apoptosis before the dose-response relationship and threshold were analyzed.Results In the dose range of 0.1 to 2 Gy,the number of peripheral blood white blood cells and lymphocytes decreased at 3 and 7 days after irradiation and the ratio of granulocytes to erythrocytes in bone marrow and bone marrow cell subsets were abnormal as the dose increased.Seven days after irradiation,the platelet count decreased.The minimum dose that caused significant changes was 0.5 Gy,13 models with dose-response relationships were obtained,and the minimum values of ED25,ED50 and ED63 were 0.25,0.58 and 0.76 Gy,respectively.Conclusion A total of 13 dose-response relationship models of proton-induced bone marrow injury in mice have been obtained,and the dose threshold of proton-induced bone marrow injury ranges from 0.25 to 0.76 Gy.