Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Objective:To investigate the mode and timing of delivery in pregnant women with complex fetal congenital heart disease (CHD) detected by prenatal ultrasound.Methods:The clinical data of 123 fetuses with complex CHD detected by prenatal ultrasound in Peking University People′s Hospital from January 2016 to December 2023 were retrospectively analyzed. Pregnant women with indications for prenatal diagnosis underwent G-banding karyotype analysis, single nucleotide polymorphism array (SNP arrry) or whole exome sequencing after informed consent. Integrated managements were provided for pregnant women with complex CHD during pregnancy and perinatal period, and to determine the mode and timing of delivery. Infants with complex CHD received timely treatment or referral after birth.Results:The gestational age at ultrasound diagnosis of the 123 fetuses with complex CHD was (23.7±3.4) weeks. There were 11 cases (8.9%) of total anomalous pulmonary venous connection (TAPVC), 14 cases (11.4%) of anomalous pulmonary valve (PVA), 7 cases (5.7%) of right ventricle double outlet (RVDO), 13 cases (10.6%) of anomalous aortic arch, 69 cases (56.1%) of transposition of the great arteries (TGA), 9 cases (7.3%) of other types. All cases were treated with fetal preservation after prenatal consultation. Among the 72 cases undergoing prenatal diagnosis, 9 cases (12.5%) had chromosomal variations. Fifty-five cases (44.7%, 55/123) underwent trial of labor, of which 46 cases (37.4%, 46/123) had successful vaginal delivery, including 6 cases of forceps delivery, and other 9 cases of failed trial of labor transferred to cesarean section. A total of 77 cases of pregnant women underwent cesarean section. Except for the 21 cases of pregnant women who asked for cesarean section, the cesarean section rate of pregnant women with complex CHD was 45.5% (56/123), which was not significantly different from the average cesarean section rate of the same period in our hospital (40.2%; χ2=7.34, P=0.270). The gestational age at delivery of the 123 fetuses with complex CHD was (37.9±1.4) weeks, the birth weight of the neonates was (3 099±480) g, and the umbilical artery blood pH value was 7.31±0.05. The oxygen saturation of 86 cases before and after alprostadil infusion were (72.8±6.0)% and (80.5±5.0)%, respectively, and the difference was statistically significant ( t=4.38, P<0.001). One hundred and fourteen children underwent surgical treatment, 112 of them (98.2%) had good postoperative reexamination. Only 2 cases (1.8%) died after surgery, and 14.0% (16/114) had the possibility of secondary surgery. Conclusions:Fetal complex CHD is not an indication for cesarean section, and the delivery mode could be selected according to the obstetric situation. If the mother and child are in stable condition, the delivery is planned after 39 weeks of gestation. For children with low oxygen saturation after birth, alprostadil could be pumped to maintain the open ductus arteriosus, and timely referral to the pediatric cardiac surgery for subsequent surgical treatment, which could achieve a good prognosis.

Objective:To investigate the mode and timing of delivery in pregnant women with complex fetal congenital heart disease (CHD) detected by prenatal ultrasound.Methods:The clinical data of 123 fetuses with complex CHD detected by prenatal ultrasound in Peking University People′s Hospital from January 2016 to December 2023 were retrospectively analyzed. Pregnant women with indications for prenatal diagnosis underwent G-banding karyotype analysis, single nucleotide polymorphism array (SNP arrry) or whole exome sequencing after informed consent. Integrated managements were provided for pregnant women with complex CHD during pregnancy and perinatal period, and to determine the mode and timing of delivery. Infants with complex CHD received timely treatment or referral after birth.Results:The gestational age at ultrasound diagnosis of the 123 fetuses with complex CHD was (23.7±3.4) weeks. There were 11 cases (8.9%) of total anomalous pulmonary venous connection (TAPVC), 14 cases (11.4%) of anomalous pulmonary valve (PVA), 7 cases (5.7%) of right ventricle double outlet (RVDO), 13 cases (10.6%) of anomalous aortic arch, 69 cases (56.1%) of transposition of the great arteries (TGA), 9 cases (7.3%) of other types. All cases were treated with fetal preservation after prenatal consultation. Among the 72 cases undergoing prenatal diagnosis, 9 cases (12.5%) had chromosomal variations. Fifty-five cases (44.7%, 55/123) underwent trial of labor, of which 46 cases (37.4%, 46/123) had successful vaginal delivery, including 6 cases of forceps delivery, and other 9 cases of failed trial of labor transferred to cesarean section. A total of 77 cases of pregnant women underwent cesarean section. Except for the 21 cases of pregnant women who asked for cesarean section, the cesarean section rate of pregnant women with complex CHD was 45.5% (56/123), which was not significantly different from the average cesarean section rate of the same period in our hospital (40.2%; χ2=7.34, P=0.270). The gestational age at delivery of the 123 fetuses with complex CHD was (37.9±1.4) weeks, the birth weight of the neonates was (3 099±480) g, and the umbilical artery blood pH value was 7.31±0.05. The oxygen saturation of 86 cases before and after alprostadil infusion were (72.8±6.0)% and (80.5±5.0)%, respectively, and the difference was statistically significant ( t=4.38, P<0.001). One hundred and fourteen children underwent surgical treatment, 112 of them (98.2%) had good postoperative reexamination. Only 2 cases (1.8%) died after surgery, and 14.0% (16/114) had the possibility of secondary surgery. Conclusions:Fetal complex CHD is not an indication for cesarean section, and the delivery mode could be selected according to the obstetric situation. If the mother and child are in stable condition, the delivery is planned after 39 weeks of gestation. For children with low oxygen saturation after birth, alprostadil could be pumped to maintain the open ductus arteriosus, and timely referral to the pediatric cardiac surgery for subsequent surgical treatment, which could achieve a good prognosis.

AIM To explore the clinical effects of oral administration and enema of Tongfu Paiqi Mixture on patients with acute exacerbation of chronic obstructive pulmonary disease complicated with gastrointestinal dysfunction.METHODS One hundred and eight patients were randomly assigned into control group(54 cases)for 5-day intervention of both oral administration and enema of Tongfu Paiqi Mixture simulant and conventional treatment,and observation group(54 cases)for 5-day intervention of both oral administration and enema of Tongfu Paiqi Mixture and conventional treatment.The changes in clinical effects,GIDS score,Phlegm and Blood Stasis Obstructing Lung Syndrome score,gastrointestinal mucosal barrier serum markers(DAO,D-LA,IFABP),intra-abdominal pressure,gastrointestinal hormones(MTL,GAS,VIP),inflammatory factors(IL-1β,IL-6,TNF-α,PCT),pulmonary function indices(FEV1、FEV1％)and PaO2/FiO2 were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased GIDS score,Phlegm and Blood Stasis Obstructing Lung Syndrome score,intra-abdominal pressure,VIP,gastrointestinal mucosal barrier serum markers,inflammatory factors(P＜0.05),and increased MTL,GAS,pulmonary function indices,PaO2/FiO2(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the patients with acute exacerbation of chronic obstructive pulmonary disease complicated with gastrointestinal dysfunction,the oral administration and enema of Tongfu Paiqi Mixture can regulate gastrointestinal hormones,reduce inflammatory degree,protect intestinal barrier functions,alleviate clinical symptoms,and improve pulmonary functions.

AIM To explore the clinical effects of oral administration and enema of Tongfu Paiqi Mixture on patients with acute exacerbation of chronic obstructive pulmonary disease complicated with gastrointestinal dysfunction.METHODS One hundred and eight patients were randomly assigned into control group(54 cases)for 5-day intervention of both oral administration and enema of Tongfu Paiqi Mixture simulant and conventional treatment,and observation group(54 cases)for 5-day intervention of both oral administration and enema of Tongfu Paiqi Mixture and conventional treatment.The changes in clinical effects,GIDS score,Phlegm and Blood Stasis Obstructing Lung Syndrome score,gastrointestinal mucosal barrier serum markers(DAO,D-LA,IFABP),intra-abdominal pressure,gastrointestinal hormones(MTL,GAS,VIP),inflammatory factors(IL-1β,IL-6,TNF-α,PCT),pulmonary function indices(FEV1、FEV1％)and PaO2/FiO2 were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased GIDS score,Phlegm and Blood Stasis Obstructing Lung Syndrome score,intra-abdominal pressure,VIP,gastrointestinal mucosal barrier serum markers,inflammatory factors(P＜0.05),and increased MTL,GAS,pulmonary function indices,PaO2/FiO2(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the patients with acute exacerbation of chronic obstructive pulmonary disease complicated with gastrointestinal dysfunction,the oral administration and enema of Tongfu Paiqi Mixture can regulate gastrointestinal hormones,reduce inflammatory degree,protect intestinal barrier functions,alleviate clinical symptoms,and improve pulmonary functions.

AIM To explore the clinical effects of Yiqi Huoluluo Mingmu Decoction combined with Conbercept Ophthalmic Injection on patients with non-proliferative diabetic retinopathy.METHODS One hundred and sixty-seven patients were randomly assigned into control group(83 cases)for administration of Conbercept Ophthalmic Injection,and observation group(84 cases)for administration of both Yiqi Huoluluo Mingmu Decoction and Conbercept Ophthalmic Injection.The changes in clinical effects,miR-15b,CTGF,VEGF,hemodynamic indices(PSV,EDV,RI),visual field gray value,CMT,hemangioma count,blood spot area,BCVA,electroretinograms(amplitudes of a wave,b wave under light-dark adaptation),TCM symptom scores and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased miR-15b,PSV,EDV,BCVA,electroretinograms(P＜0.05),and increased CTGF,VEGF,RI,visual field gray value,CMT,hemangioma count,blood spot area,TCM symptom scores(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with non-proliferative diabetic retinopathy,Yiqi Huoluluo Mingmu Decoction combined with Conbercept Ophthalmic Injection can improve hemodynamics,reduce fundus lesions,and regulate miR-15b,VEGF expressions.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies. Heat shock protein 90 (Hsp90) as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance. Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance. In this study, a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX, and a COA-modified 4-arm PEG polymer (4PSC) was synthesized. COA, an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression, was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity. Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity. By blocking the Hsp90 signaling pathway, 4PSC significantly enhanced the antitumor effect of PTX, inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro. Remarkable results were further confirmed in vivo with two preclinical tumor models. These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.

Aim To explore the effect of gypenosides on proliferation and apoptosis of human gastric cancer cells SGC-7901 and AGS and its mechanism. Methods Different concentrations of gypenosides were cultured with human gastric cancer cells SGC-7901 and AGS. Cell viability assay was used to detect cell proliferation activity, and the IC