ObjectiveTo explore the effects of Bushen Tiaojing Formula （补肾调经方） on the quality of early embryos in repeated controlled ovarian stimulation （COS） and its possible mechanism. MethodsA total of 150 ICR female mice were divided into a normal group， a model group， an inhibitor group， a low-dose and a high-dose Bushen Tiaojing Formula group. Mice in the normal group， inhibitor group and model group were gavaged with distilled water 0.25 ml a day， and mice in the low- and high-dose groups were given 25.6 and 51.2 g/（kg·d） of Bushen Tiaojing Formula， respectively. All groups were gavaged once a day for 13 days as a cycle. Mice in the normal group were injected intraperitoneally with 0.1 ml normal saline on the 11th day of gavage， while mice in the other four groups were used to establish COS models. The inhibitor group was injected with the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid 0.2 ml one hour before modelling. All groups were injected by gavage and intraperitoneal injection for 3 consecutive cycles， with an interval of 4 days between cycles. Immediately after the third intraperitoneal injection， mice were grouped with male mice of the same strain in a ratio of 2∶1， and at 8AM of the second day， the mice were examined， and those with spermatozoa or spermatozoa in the vaginal smears were recorded as pregnant. The mice were executed in the afternoon of the 4th day of pregnancy， and the blastocysts were obtained under an inverted microscope. The morphology of the blastocysts was observed， and the total number of blastocysts and the number of high-quality blastocysts were recorded to calculate the rate of high-quality blastocysts； the apoptosis of blastocyst cells was detected by the Tunel method， and the apoptosis rate was calculated； the endoplasmic reticulum molecular chaperone protein glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， B-lymphoblastoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cystathionin 3 （Caspase-3） and cystathionin 12 （Caspase-12） protein levels and their mRNA expression were detected by immunofluorescent assay and RT-qPCR assay， respectively. ResultsIn the normal group， blastocysts had regular morphology， good morphological development and low fragmentation rate； in the model group， blastocysts were poorly developed， cell morphology was irregular， fragmentation rate was high， and there was some stagnation； in the inhibitor group and high-dose， low-dose Bushen Tiaojing Formula groups， cell morphology could be seen to be better developed， with regular morphology and less fragmentation rate. Compared with the normal group， the rate of high-quality blastocysts in the model group reduced， the rate of apoptosis of blastocyst cells increased， the levels of GRP78， CHOP， Caspase-12， Caspase-3， Bax protein and its mRNA expression in blastocysts increased， while the level of Bcl-2 protein and its mRNA reduced （P＜0.01）. Compared with the model group， the rate of high-quality blastocysts increased， the rate of apoptosis of blastocysts decreased， the levels of GRP78， CHOP， Caspase-12， Caspase-3， Bax protein and their mRNA expression decreased， and the levels of Bcl-2 protein and its mRNA expression increased in the blastocysts in the inhibitor group and the high-dose and low-dose Bushen Tiaojing Formula groups （P＜0.01）. Compared with the inhibitor group， GRP78， CHOP， Caspase-12， Bax protein levels and their mRNA expressions increased in the high-dose Bushen Tiaojing Formula group， and Caspase-12， Caspase-3， Bax protein levels and their mRNA expressions increased in the low-dose formula group （P＜0.05 or P＜0.01）. ConclusionBushen Tiaojing Formula can inhibit the apoptosis of blastocyst cells caused by repeated controlled ovarian stimulation by improving endoplasmic reticulum stress， which plays a role in improving the quality of early embryos.

Objective To develop a self-assessment scale of home volume management for patients with chronic heart failure(CHF),and to test its reliability and validity.Methods With the self-care theory as the theoretical framework,the initial scale was developed through literature analysis,qualitative interview and expert consultation.A questionnaire survey was conducted on 598 patients with CHF who were treated or reviewed in a tertiary hospital in Hangzhou from September 2022 to January 2023 to test the reliability and validity of the scale.Results The exploratory factor analysis extracted 4 common factors with the cumulative variance contribution rate of 61.268％.The results of confirmatory factor analysis showed that the main evaluation indicators were all within the acceptable range of the judgment standard.The item-level content validity index ranged from 0.853 to 1.000;the scale-level content validity index/average was 0.951.The Cronbach's a coefficient,half reliability and retest reliability of the overall scale were 0.930,0.723 and 0.867,respectively.Conclusion The self-rating scale of home volume management for CHF patients has good reliability and validity,and it can effectively assess the level of home volume management for CHF patients.

Objective:To observe the characteristics and differences of gut microbiota in asthma patients with different inflammatory types through metagenomic analysis.Methods:Adults aged ≥18 years who visited the Respiratory Clinic of Peking University Third Hospital from August 1, 2021 to August 31, 2022 and were primarily diagnosed with asthma were selected as the study subjects. Finally, 29 patients with stable asthma were included. Fresh fecal samples were collected and the fecal DNA was extracted for high-throughput 16sRNA sequencing of gut microbiota. The diversity and community structure of gut microbiota in different groups of asthma patients were compared, and the species differences were analyzed through random forest and LEfSe analysis.Results:There were sex-based differences in asthma patients with different types of inflammation, and the proportion of female patients was higher in neutrophilic asthma patients ( χ2=4.14, P=0.042). There was no significant intergroup difference in the alpha diversity of gut microbiota among asthma patients with different inflammatory types, but there were significant differences in the microbiome. Patients with neutrophilic asthma had higher relative abundance of Bacillales ( P=0.029) and Oscillospiraceae ( P=0.015). In species LEfSe analysis, patients with eosinophilic asthma had a higher relative abundance of fungi. Conclusion:There are intergroup differences in the gut microbiota of asthma patients with different inflammation types, and fungi are biomarkers that distinguish the differences in gut microbiota between patients with eosinophilic asthma and neutrophilic asthma.

ObjectiveTo use the maternal morbidity WOICE Tool（Chinese version）to investigate the maternal morbidity in Shanghai， and to examine the current situation and associated factors of adverse symptoms and impaired functioning in the third trimester and postpartum period. MethodsPregnant women who made their initial visit and established a medical record at a tertiary obstetrics and gynecology hospital in Shanghai from March to August 2021 were recruited and a baseline survey was completed. The prevalence of maternal morbidity was surveyed in the third trimester and first 6 weeks postpartum. ResultsSelf-reported adverse physical symptoms were observed in 89.8% of women in the third trimester and 86.1% in first 6 weeks postpartum. The prevalence rates of anxiety and depression were 4.1% and 6.2% in the third trimester， and 6.2% and 7.5% in first 6 weeks postpartum， respectively. The proportions of women reporting impaired functioning were 80.3% in the third trimester and 64.1% in first 6 weeks postpartum， respectively. Physical symptoms were associated with parity， education， the newborn’s health status， and risk of experiencing violence. Psychological symptoms were associated with age， household responsibilities， employment status， the newborn’s health status， pre-pregnancy body mass index （BMI）， and risk of experiencing violence. Functionality was associated with the type of registered residence， education level， household responsibilities， and risk of experiencing violence. ConclusionThe physical health status of pregnant and postpartum women in Shanghai is better than that in the middle-income regions abroad， with anxiety and depression at average levels compared to national statistics in China. Physical， psychological， and functional status are affected by multiple factors including personal， health， family， and work conditions. Preventive measures should be taken from various perspectives to mitigate adverse symptoms and impaired functioning， and to improve the positive experience of pregnancy and childbirth.

Objective To construct a rat model of trigeminal neuralgia(TN)to explore the expression of high-mobility group box-1(HMGB1)in the trigeminal ganglion(TG)and the possible mechanism of HMGB1's effect on pain.Methods TN model was constructed by infraorbital nerve constriction and divided into operation group(CCI group)and Sham group,and the success of the model construction was determined through mechanical pain thresh-old assessment.Real time fluorescence quantitative PCR(RT-qPCR)and Western blot were used to detect high mobility group protein B1(HMGB1),Toll receptor 4(TLR4),and Nuclear Factor Kappa B(NF-κB)mRNA and protein expression in the ipsilateral trigeminal ganglion(TG)of the Sham and CCI rats.50 mg/kg HMGB1 inhibi-tor glycyrrhizin(GL)was injected intraperitoneally every day for two weeks,and normal saline(NS)was used as control.The patients were divided into CCI group,CCI+NS group and CCI+GL group.HMGB1,TLR4,and NF-κB mRNA and protein expression in the ipsilateral trigeminal ganglion(TG)were detected by RT-qPCR and West-ern blot in CCI group,CCI+NS group,and CCI+GL group.Results The mechanical threshold on the operated side of the rat continued to decrease(P<0.05),and mechanical pain threshold identification model was success-fully constructed.After chronic compressive injury to the infraorbital nerve in rats,HMGB1,TLR4,and NF-κB mRNA and protein expression in TG on the operated side increased(P<0.05);After administration of HMGB1 inhibitor Glcyrrhizin,HMGB1,TLR4,NF-κB showed a decrease(P<0.05).Conclusion HMGB1 is associat-ed with TN,and HMGB1 may be involved in the pathogenesis of TN through TLR4/NF-κB signaling pathway.

Objective To investigate the pathological role of detect protein kinase C(PKC)/ transient receptor po-tential vanilloid subtype 1(TRPV1) pathway in trigeminal neuralgia (TN) in rats.Methods The infraorbital nerve-chronic constriction injury (ION-CCI) was used to establish a rat model of TN.The rats were randomly di-vided into Sham group,CCI group, CCI+DMSO group and CCI+GF109203X (a PKC inhibitor) group.The me-chanical pain threshold of the rats was measured using a Von Frey brush.qRT-PCR and Western blot were used to detect PKC and TRPV1 in the trigeminal ganglion (TG) .HE staining was used to observe the pathological changes of TG.Results The mechanical pain threshold significantly decreased (P <0.05), and the expression of phos-phorylated PKC(p-PKC) and TRPV1 in TG significantly increased in the CCI group (P<0.05).Histopathological results showed that compared with the Sham group,the CCI group observed significant changes in TG such as in-creased inflammatory cell infiltration and nerve cell swelling.Injection of GF109203X effectively reduced the phos-phorylation of PKC and the expression of TRPV1 in the TG of rats, and the mechanical pain threshold of the rats in-creased (P<0.05) .Under the light microscope, cell swelling and inflammatory cells in the TG were reduced.Conclusion PKC/TRPV1 pathway may be involved in trigeminal neuralgia in rats.

Objective : To study the role of Toll⁃like receptor 7 (TLR7) in trigeminal nerve pain in SD rats , and to explore the mechanism of TLR7 mediating related inflammatory factors through the activation of NF⁃κB pathway during the process of pain. Methods : The rat model of trigeminal neuralgia (TN) was established by infraorbital nerve constriction injury(ION⁃CCI) . The expression of TLR7 in trigeminal ganglion (TG) was detected by qRT⁃PCR and Western blot. Hydroxychloroquine (HCQ) , an inhibitor of TLR7 , was given to ION⁃CCI rats by intragastric administration. The expression of TLR7 and its downstream signal pathway NF⁃κB subunit p65 , p ⁃p65 and inflammatory factors (TNF⁃α , IL⁃1β) in TG were detected. Results : After trigeminal nerve injury induced by ligation of infraorbital nerve , the expression of TLR7 in TG of rats significantly increased. After administration of TLR7 inhibitor, the expression of TLR7 , TNF⁃α and IL⁃1β in TG decreased , the translocation and phosphorylation of p65 nucleus decreased , the activation of NF⁃κB signal pathway was inhibited , and the mechanical pain induced by ION⁃CCI was relieved in male SD rats. Conclusion TLR7 in TG regulates neuropathic pain by activating NF⁃κB signal pathway in primary sensory neurons and mediating the expression of inflammatory cytokines TNF⁃α and IL⁃1β .

Objective:To investigate the changes of T helper cell (Th), regulatory T-cell (Treg cell) related cytokines in vaginal lavage fluid of patients with high risk-human papilloma virus 16 (HR-HPV16) positive and its predictive effect on the development of cervical neoplasms.Methods:A total of 200 cases of HR-HPV16 positive patients who admitted to Xingtai People's Hospital from January 2022 to December 2022 were selected as the experimental group. According to the results of pathological examination, all patients in the experimental group were divided into non pathological group (78 cases), low grade squamous intraepithelial lesion (LSIL) group (49 cases), high grade squamous intraepithelial lesion (HSIL) group (39 cases) and cervical cancer group (34 cases); and 100 healthy people undergoing the physical examination in the same period were taken as the healthy control group. Enzyme-linked immunosorbent assay (ELISA) double-antibody sandwich method was used to detect the levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) and transforming growth factor β (TGF-β) in vaginal lavage fluid of patients in different groups. Multivariate logistics regression was used to analyze the risk factors of cervical cancer, and a nomogram model was established. The receiver operating characteristics (ROC) curve was drawn with pathological results as the gold standard, and the area under the curve (AUC) was calculated to evaluate the predictive ability of the nomogram model.Results:The levels of IL-6, IL-10, IL-17, TNF-α, TGF-β in vaginal lavage fluid of patients in the experimental group were higher than those in the healthy control group, while the levels of IL-2, IL-12 and IFN-γ in the experimental group were lower than those in the healthy control group, and the differences were statistically significant (all P < 0.05); the difference in IL-4 level of both groups was not statistically significant ( P > 0.05). There were statistically significant differences in IL-6, IL-10, IL-17, TNF-α, TGF-β, IL-2, IL-12 and IFN-γ among non pathological group, LSIL group, HSIL group and cervical cancer group (all P < 0.05); the levels of IL-6, IL-10, IL-17, TNF-α, TGF-β in cervical cancer group were the highest, the levels of IL-2, IL-12 and IFN-γ were the lowest; the level of IL-4 in non pathological group, LSIL group, HSIL group and cervical cancer group had no statistically significant difference ( P > 0.05). Logistics regression analysis showed that low IL-2, high IL-4, high IL-6, high IL-10, low IL-12, high IL-17, high TNF-α, low IFN- γ and low TGF-β expressions in vaginal lavage fluid of patients with HR-HPV16 positive were independent risk factors for the development of cervical cancer (all P < 0.05). The results of nomogram analysis showed that IL-6, IL-10, IL-17, TNF-α, TGF-β in vaginal lavage fluid were the factors predicting the development of cervical cancer in HR-HPV16 positive patients. The ROC curve analysis showed that the AUC of nomogram model in predicting the development of cervical cancer in HR-HPV16 positive patients was 0.945 (95% CI 0.901-0.988), and the predictive efficacy was good. Conclusions:Th and Treg cell related cytokines levels in vaginal lavage fluid of patients with HR-HPV16 positive show pathological changes in cervical cancer patients and the above indicators have a high value in predicting the development of cervical cancer.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objective To study the value of postmortem imaging on the diagnosis of intestinal perforation.Method Postmortem imaging(PMCT and PMCTA)data of 2 intestinal perforation deaths(and 4 controlled cases)were reviewed retrospectively.Diagnosing capacities of intestinal perforation by postmortem imaging method were further investigated.Results PMCT is sensitive in detecting the free air and liquid induced by intestinal perforation.PMCT can sometimes detect the gravity-dependent purulent secretions in the abdominopelvic cavity.PMCTA can visualize the extravasation of contrast agent from the perforation,which can be used to locate the accurate perforation region.Conclusion Postmortem imaging method(PMCT and PMCTA)is an important tool for the diagnosis of intestinal perforation,which can not only be used as a forensic diagnosis method,but is also useful to locate the perforation site before an forensic autopsy.