ObjectiveTo investigate the role of the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway in intestinal mucosal barrier damage in ulcerative colitis， as well as the intervention mechanism of Shaoyaotang. MethodsSixty SD rats were allocated into a blank group， a model group， a mesalazine （0.42 g·kg^-1） group， and low-， medium-， and high-dose （11.1， 22.2， 44.4 g·kg^-1， respectively） Shaoyaotang groups. A model of ulcerative colitis was induced by 2，4，6-trinitrobenzenesulfonic acid （TNBS）. After successful modeling， rats were administrated with corresponding agents via gavage for 7 days. Changes in colon length and colon weight were observed. Hematoxylin-eosin staining was performed to examine the pathological changes of the colon， and immunohistochemistry was employed to detect the expression of the inflammatory cytokine interleukin-8 （IL-8）， cyclooxygenase-2 （COX-2）， junction adhesion molecule-1 （JAM-1）， and claudin-1 in the colon. Western blot analysis was performed to determine the protein levels of TLR4， MyD88， and NF-κB in the colon. ResultsCompared with the blank group， the model group showed elevated DAI score （P<0.01）， reduced colon length and colon weight （P<0.01）， down-regulated protein levels of JAM-1 and claudin-1 （P<0.01）， and up-regulated protein levels of IL-8， COX-2， TLR4， MyD88， and NF-κB p65 （P<0.01） in the colon tissue. Compared with the model group， each treatment group showed decreased DAI score （P<0.05， P<0.01）， increased colon length and colon weight （P<0.05， P<0.01）， up-regulated protein levels of JAM-1 and claudin-1 （P<0.01）， and down-regulated protein levels of IL-8， COX-2， TLR4， MyD88， and NF-κB p65 （P<0.01） in the colon tissue. ConclusionShaoyaotang alleviates intestinal inflammation and intestinal mucosal damage to protect intestinal barrier integrity by regulating the TLR4/MyD88/NF-κB signaling pathway.

Objective To analyze the pathogenic characteristics of measles virus genotype D8 in three cases in Hubei Province. Methods An epidemiological investigation was conducted on three consecutive confirmed cases of measles in a city of Hubei Province within a week. Measles virus IgM antibody was detected by enzyme-linked immunosorbent assay, the measles virus nucleic acid was detected by real-time fluorescent quantitative polymerase chain, and the reverse transcription polymerase chain reaction was used to amplify the C-terminal 450-nucleotide sequence of the N gene. A phylogenetic tree of measles virus genotypes was constructed to compare the isolated strains with reference strains of measles from other regions, and the nucleotide homology and genotype were analyzed. Results The nucleotide homology of the N gene of three measles virus strains in Hubei Province in 2025 was 99.80%-100.00%, with one amino acid site difference. The N gene homology with the Swiss strain (MVs/Bern.CHE/19.23D8) and the Japanese strain (MVs/Tokyo.JPN/24.23/23124/D8) was 99.3% -99.7%, with one amino acid site difference. The nucleotide homology of N gene with the WHO D8 genotype reference strain (MVi/Manchester.GBR/30.94/D8) was 98.00%-98.20%, with six amino acid differences. The nucleotide homology of the N gene compared with the vaccine strain Shanghai-191 was 91.40%-91.60%, with 21 amino acid differences from the vaccine strain S191. Conclusion All the three measles virus strains in Hubei Province are of the genotype D8 and have a high homology. It is necessary to pay attention to imported cases of measles, and the etiological monitoring of measles virus should be continuously strengthened to provide a scientific basis for the elimination of measles.

Objective:To analyze the clinical characteristics, diagnosis and prognosis of pregnant women with fetomaternal hemorrhage (FMH) syndrome, and to guide the management of pregnant women with FMH syndrome.Methods:The clinical data of 33 pregnant women with FMH syndrome admitted to Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from January 2010 to December 2024 were collected, and the general information, diagnostic characteristics, treatment and maternal and fetal prognosis were retrospectively analyzed.Results:The incidence of FMH syndrome in our hospital was 1.7/10 000 (33/194 272). The gestational age of onset of FMH syndrome in 33 pregnant women was (35.6±3.1) weeks, 15 cases (45%, 15/33) were full-term delivery and 18 cases (55%, 18/33) were preterm delivery. Decreased fetal movement (51%, 17/33) was the most common initial symptom, followed by abnormal electronic fetal monitoring (33%, 11/33). Thirty-two cases (97%, 32/33) underwent cesarean section, and only one case had spontaneous delivery. Postpartum hemorrhage occurred in 11 cases (33%, 11/33). All the neonates were transferred to neonatal intensive care unit for treatment. Two of them were treated with intrauterine blood transfusion, and the neonates did not receive blood transfusion after birth. The neonatal mortality rate was 6% (2/33), and the remaining 31 cases (94%, 31/33) survived. Complications occurred in 3 premature infants, including 1 case of neonatal neurodevelopmental disorder with cochlear implantation, 1 case of pulmonary artery stenosis, and 1 case of retinopathy of prematurity. Three pregnant women were pregnant again, and none of them had FMH syndrome.Conclusions:Decreased fetal movement or abnormal electronic fetal monitoring in late pregnancy should be alert to the occurrence of FMH syndrome. Early diagnosis and intervention are critical to improve the prognosis of FMH syndrome.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective:To analyze the clinical characteristics, diagnosis and prognosis of pregnant women with fetomaternal hemorrhage (FMH) syndrome, and to guide the management of pregnant women with FMH syndrome.Methods:The clinical data of 33 pregnant women with FMH syndrome admitted to Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from January 2010 to December 2024 were collected, and the general information, diagnostic characteristics, treatment and maternal and fetal prognosis were retrospectively analyzed.Results:The incidence of FMH syndrome in our hospital was 1.7/10 000 (33/194 272). The gestational age of onset of FMH syndrome in 33 pregnant women was (35.6±3.1) weeks, 15 cases (45%, 15/33) were full-term delivery and 18 cases (55%, 18/33) were preterm delivery. Decreased fetal movement (51%, 17/33) was the most common initial symptom, followed by abnormal electronic fetal monitoring (33%, 11/33). Thirty-two cases (97%, 32/33) underwent cesarean section, and only one case had spontaneous delivery. Postpartum hemorrhage occurred in 11 cases (33%, 11/33). All the neonates were transferred to neonatal intensive care unit for treatment. Two of them were treated with intrauterine blood transfusion, and the neonates did not receive blood transfusion after birth. The neonatal mortality rate was 6% (2/33), and the remaining 31 cases (94%, 31/33) survived. Complications occurred in 3 premature infants, including 1 case of neonatal neurodevelopmental disorder with cochlear implantation, 1 case of pulmonary artery stenosis, and 1 case of retinopathy of prematurity. Three pregnant women were pregnant again, and none of them had FMH syndrome.Conclusions:Decreased fetal movement or abnormal electronic fetal monitoring in late pregnancy should be alert to the occurrence of FMH syndrome. Early diagnosis and intervention are critical to improve the prognosis of FMH syndrome.

Objective:To study and screen the differential expression of inflammatory proteins in diabetes skin ulcers and common skin ulcers, so as to provide experimental basis for further research on anti-inflammatory and healing drug targets of diabetes skin ulcers.Methods:The tissues of 11 patients with diabetes skin ulcer, 12 patients with common skin ulcer and 11 patients with normal skin were collected from the First Hospital of Hunan University of Chinese Medicine. The levels of inflammatory protein Toll like receptor 4 (TLR4), nuclear factor κB (NF-κB), pro-inflammatory factor interferon -γ (IFN -γ), tumor necrosis factor - α (TNF -α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β), macrophage chemotactic protein-1 (MCP-1), anti-inflammatory factors epidermal growth factor (EGF), interleukin-4 (IL-4), and interleukin-10 (IL-10) were detected in three groups of tissues using enzyme-linked immunosorbent assay (ELISA).Results:Compared with normal tissues, the concentrations of TLR4, NF-κB, IFN -γ, TNF -α, IL-1β, IL-6, IL-8, MCP-1 and EGF in common ulcer skin tissues and diabetes ulcer tissues were higher, and the concentrations of IL-10 were lower, with statistically significant differences (all P<0.05); Compared with the normal tissue, the concentration of IL-4 in diabetes ulcer tissue was lower, the difference was statistically significant ( P<0.05); Compared with ordinary ulcer skin tissue, the concentrations of TLR4, NF-κB and MCP-1 in diabetes ulcer tissue were higher, and the concentrations of IL-4 were lower, with statistically significant differences (all P<0.05). Conclusions:The skin ulcer in diabetes patients will have inflammatory reaction, and high glucose promotes the inflammatory reaction of skin ulcer, which may be related to the abnormal expression of TLR4, NF-κB, MCP-1 and IL-4. TLR4/NF-κB signal pathway and inflammatory factors MCP-1 and IL-4 may be the target of the inflammation regulation of diabetes skin ulcer.

Objective:This study aimed to investigate the pathogen types in patients diagnosed with clinical viral encephalitis (VE) in Hubei province from 2011 to 2023 through laboratory tests, and analyze the epidemiological characteristics of confirmed cases.Methods:The serum and cerebrospinal fluid (CSF) samples from reported VE cases were collected in Hubei province from 2011 to 2023. All serum and/or CSF samples of the collected VE cases were screened for Japanese encephalitis virus (JEV) IgM antibodies using the enzyme-linked innunosorbent assay (ELISA), and the detection of the viral genes of JEV using reverse transcription polymerase chain reaction (RT-PCR). Seven other pathogens including herpes simplex virus, mumps virus, coxsackievirus, echovirus, Epstein-Barr virus, cytomegalovirus and varicella zoster virus were detected in serum samples from VE cases excluded from JEV infection. Epidemiological analysis was conducted on laboratory-confirmed cases of VE.Results:From 2011 to 2023, ninety-seven VE cases were collected in the Hubei province. The result of serological (JEV-specific IgM) and genetic testing for JEV showed that 64.9% (63/97)of the collected cases were confirmed as JEV infection. Among the thirty-four cases of non-JEV infection, six viruses were detected in the serum of ten cases. The remaining twenty-four cases were classified as unknown VE cases. Our analysis indicated that those aged 0-15 years were the majority of laboratory-confirmed Japanese encephalitis (JE) cases. However, the incidence of these cases in the >40 years age group has increased in recent years. The temporal distribution of laboratory-confirmed cases of JE revealed that the majority of cases occurred from February to September each year, with the highest incidence in July to August.Conclusions:JE has been the predominant cause of VE in Hubei province over the past decade. Our findings will provide critical baseline data for the prevention and control of VE in Hubei province.

Objective:To evaluate the efficacy and safety of intensity modulated radiotherapy (IMRT) and programmed death-1 (PD-1) immunotherapy combined with single-agent chemotherapy for patients with local failure of esophageal cancer after initial radical chemoradiotherapy.Methods:Clinical data of 80 patients with local failure of esophageal cancer after initial radical chemoradiotherapy treated with IMRT or PD-1 immunotherapy combined with single-agent chemotherapy in People's Hospital of Xinghua between June 2014 and June 2023 were retrospectively analyzed. IMRT was delivered at 1.8-2.0 Gy per fraction, 5 fractions per week, with a total dose of 45.0-60.0 Gy in 40 patients (IMRT group). The other 40 patients received PD-1 immunotherapy combined with single-agent chemotherapy (PD-1 immunotherapy combined with single-agent chemotherapy group). Kaplan-Meier method was used for univariate analysis and the cumulative survival probability. Log-rank test was used for survival significance test. Cox proportional hazards model was used for multivariate analysis of related factors affecting overall survival (OS), progression-free survival (PFS) and local control (LC).Results:By December 2023, the follow-up rate was 100%. The 1- and 2-year OS rates in the IMRT group were 66.1% and 18.9%, with a median OS time of 10.1 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year OS rates were 72.3% and 36.9%, with a median OS time of 12.4 months. There was a significant difference in OS rates between two groups ( χ2=3.89, P=0.049). The 1- and 2-year PFS rates in the IMRT group were 47.4% and 31.6%, with a median PFS time of 8.5 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year PFS rates were 70.0% and 64.2%, with a median PFS time of 11.9 months. There was no significant difference in the PFS rates between two groups ( χ2=2.66, P=0.103). The 1- and 2-year LC rates in the IMRT group were 68.6% and 62.3%, with a median LC time of 8.9 months. In the PD-1 immunotherapy combined with single-agent chemotherapy group, the 1- and 2-year LC rates were 72.8% and 66.7%, with a median LC time of 12.0 months. There was no significant difference in LC rates between two groups ( χ2=0.18, P=0.672). Grade 2 radiation esophagitis and radiation pneumonitis developed in 82.5% (33/40) and 32.5% (13/40) in the IMRT group, respectively. The incidence of grade 1-2 peripheral blood leukopenia was 40.0% (16/40), 50.0% (20/40) for grade 1-2 peripheral blood thrombocytopenia, 27.5% (11/40) for moderate to severe anemia, and 20.0% (8/40) for grade 1-2 thyroid dysfunction in the PD-1 immunotherapy combined with single-agent chemotherapy, respectively. Single- and multi-factor analysis showed that the failure site ( χ2=9.01, P=0.011) and short-term efficacy ( χ2=7.78, P=0.005) were the independent prognostic factors affecting OS. The short-term efficacy was the independent prognostic factor for PFS ( χ2=31.63, P<0.001). The short-term efficacy was the independent prognostic factors affecting LCS ( χ2=17.64, P=0.001) too. Conclusion:For the patients with local failure of esophageal cancer after initial radical chemoradiotherapy, the combination of PD-1 immunotherapy with single-agent chemotherapy yields better survival prognosis than re-irradiation alone, but it is still necessary to pay attention to the related drug toxicities.

Objective:This study aimed to investigate the pathogen types in patients diagnosed with clinical viral encephalitis (VE) in Hubei province from 2011 to 2023 through laboratory tests, and analyze the epidemiological characteristics of confirmed cases.Methods:The serum and cerebrospinal fluid (CSF) samples from reported VE cases were collected in Hubei province from 2011 to 2023. All serum and/or CSF samples of the collected VE cases were screened for Japanese encephalitis virus (JEV) IgM antibodies using the enzyme-linked innunosorbent assay (ELISA), and the detection of the viral genes of JEV using reverse transcription polymerase chain reaction (RT-PCR). Seven other pathogens including herpes simplex virus, mumps virus, coxsackievirus, echovirus, Epstein-Barr virus, cytomegalovirus and varicella zoster virus were detected in serum samples from VE cases excluded from JEV infection. Epidemiological analysis was conducted on laboratory-confirmed cases of VE.Results:From 2011 to 2023, ninety-seven VE cases were collected in the Hubei province. The result of serological (JEV-specific IgM) and genetic testing for JEV showed that 64.9% (63/97)of the collected cases were confirmed as JEV infection. Among the thirty-four cases of non-JEV infection, six viruses were detected in the serum of ten cases. The remaining twenty-four cases were classified as unknown VE cases. Our analysis indicated that those aged 0-15 years were the majority of laboratory-confirmed Japanese encephalitis (JE) cases. However, the incidence of these cases in the >40 years age group has increased in recent years. The temporal distribution of laboratory-confirmed cases of JE revealed that the majority of cases occurred from February to September each year, with the highest incidence in July to August.Conclusions:JE has been the predominant cause of VE in Hubei province over the past decade. Our findings will provide critical baseline data for the prevention and control of VE in Hubei province.

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.