Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

OBJECTIVE: To observe the clinical effect of acupuncture for delayed sleep-wake phase disorder (DSWPD). METHODS: A total of 84 patients with DSWPD were randomized into an observation group (42 cases, 2 cases dropped off) and a control group (42 cases, 3 cases dropped off). On the basis of sleep hygiene education, acupuncture was applied at Shenmai (BL 62), Zhaohai (KI 6), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, while placebo acupuncture was applied at the same acupoints in the control group. The treatment lasted for 8 weeks, once every other day, 3 times a week in the 1st to 4th weeks; once every 3 days, 2 times a week in the 5th to 8th weeks. Before and after treatment, the actigraphy (ACT) indexes of objective sleep (total time of stay in bed, total sleep time, sleep efficiency, the number of awakenings and the wake time after falling asleep) and plasma cortisol (CORT) level were observed; before and after treatment and in follow-up of 1, 3 months after treatment, the scores of morningness-eveningness questionnaire (MEQ), insomnia severity index (ISI), fatigue severity scale (FSS) and Epworth sleepiness scale (ESS) were observed in the two groups. RESULTS: Compared before treatment, the total sleep time was prolonged, the sleep efficiency was improved, the number of awakenings was reduced, and the wake time after falling asleep was shortened after treatment in the observation group (P<0.01, P<0.05), and those in the observation group after treatment were superior to the control group (P<0.01, P<0.05). Compared before treatment, the MEQ scores after treatment in both groups and in the follow-up of 1, 3 months after treatment in the observation group were increased (P<0.01), and the MEQ score of each time point after treatment in the observation group was higher than the control group (P<0.01). The scores of ISI, FSS and ESS after treatment, and the scores of ISI、ESS in follow-up of 1, 3 months after treatment in the observation group were decreased compared with those before treatment (P<0.01, P<0.05), and in the observation group, the scores of ISI, FSS and ESS of each time point after treatment were lower than those in the control group (P<0.01, P<0.05). After treatment, the plasma CORT level in the observation group was decreased compared with that before treatment and that in the control group (P<0.01, P<0.05). CONCLUSION Acupuncture can improve the sleep and wake phase of patients with DSWPD, improve sleep quality and daytime function, and its mechanism may be related to the down-regulation of plasma CORT level.
Humans ; Acupuncture Therapy ; Sleep ; Acupuncture Points ; Down-Regulation ; Sleep Duration

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

To investigate the mechanism by which Cangxi Tongbi Capsules promote chondrocyte autophagy to inhibit knee osteoarthritis(KOA) progression by regulating the circRNA＿0008365/miR-1271/p38 mitogen-activated protein kinase(MAPK) pathway. The cell and animal models of KOA were established and intervened with Cangxi Tongbi Capsules, si-circRNA＿0008365, si-NC, and Cangxi Tongbi Capsules combined with si-circRNA＿0008365. Flow cytometry and transmission electron microscopy were employed to determine the level of apoptosis and observe autophagosomes, respectively. Western blot was employed to reveal the changes in the protein levels of microtubule-associated protein light chain 3(LC3)Ⅱ/Ⅰ, Beclin-1, selective autophagy junction protein p62/sequestosome 1, collagen Ⅱ, a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS-5), and p38 MAPK. The mRNA levels of circRNA＿0008365, miR-1271, collagen Ⅱ, and ADAMTS-5 were determined by qRT-PCR. Hematoxylin-eosin staining was employed to reveal the pathological changes of the cartilage tissue of the knee, and enzyme-linked immunosorbent assay to measure the levels of interleukin-1β(IL-1β) and tumor necrosis factor-alpha(TNF-α). The chondrocytes treated with IL-1β showed down-regulated expression of circRNA＿0008365, up-regulated expression of miR-1271 and p38 MAPK, lowered autophagy level, increased apoptosis rate, and accelerated catabolism of extracellular matrix. The intervention with Cangxi Tongbi Capsules up-regulated the expression of circRNA＿0008365, down-regulated the expression of miR-1271 and p38 MAPK, increased the autophagy level, decreased the apoptosis rate, and weakened the catabolism of extracellular matrix. However, the effect of Cangxi Tongbi Capsules was suppressed after interfering with circRNA＿0008365. The in vivo experiments showed that Cangxi Tongbi Capsules dose-dependently inhibited the p38 MAPK pathway, enhanced chondrocyte autophagy, and mitigated articular cartilage damage and inflammatory response, thereby inhibiting the progression of KOA in rats. This study indicated that Cangxi Tongbi Capsules promoted chondrocyte autophagy by regulating the circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit the development of KOA.
Rats ; Animals ; Chondrocytes ; Osteoarthritis, Knee/pathology* ; RNA, Circular/pharmacology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; MicroRNAs/metabolism* ; Apoptosis ; Autophagy/genetics* ; Collagen/metabolism*

Objective:To summarize the experience of surgical methods without repairing the fistula for 92 cases with gastrointestinal intrathoracic fistula.Methods:The surgical methods without repairing the fistula were performed through VATS, small incision assisted with VATS or thoracotomy. The focus of the surgery was to promote lung expansion, eliminate the residual cavity of chest cavity and keep effective drainage. After entering the chest cavity from the affected side, wash chest cavity with a large amount of warm normal saline and sterilize intermittently with iodophor to ensure the sterile environment in the pus cavity. Then completely remove the pleural cellulose or fiberboard on visceral pleura to promote lung expansion, eliminate the residual cavity of the chest cavity. The fistula was covered tightly and supported firmly by the visceral pleura on the lung. Multiple T-tubes were placed in thoracic cavity and fistula to keep effective postoperative drainage.Results:Among 92 cases, 85 cases were cured and the cure rate was 92.4% (85/92).7 cases died and the mortality rate was 7.61% (7/92). The 7 dead cases include 5 cases with esophagogastric anastomotic fistula (the death of 3 cases was cause by aortic esophagogastric fistula, the death of 1 case was cause by thoracic gastric tracheal fistula and 1 case was dead because of pulmonary infection and respiratory failure), 1 case with esophageal rupture (the cause of death was septic shock ), and 1 case with esophageal perforation(the cause of death was pulmonary infection and respiratory failure).Conclusion:Most of the surgeries without repairing gastrointestinal intrathoracic fistula are conducted simply through VATS or small incision assisted with VATS., which is safe and effective.

Objective:To investigate the factors associated with delay in anticoagulant therapy in patients with cerebral venous sinus thrombosis (CVST) and its effect on outcome.Methods:Patients with CVST admitted to Changhai Hospital, Naval Medical University from January 2010 to August 2021 were retrospectively enrolled. Patients were divided into early anticoagulation group and late anticoagulation group by the median time interval from first symptom to initiation of anticoagulation. The modified Rankin Scale was used for outcome assessment at 90 d after onset. 0-2 scores were defined as good outcome and 3-6 were defined as poor outcome. Demographic and clinical data were compared for the early versus late anticoagulation group and for the good versus poor outcome groups. Multivariable logistic regression was used to identify independent influencing factors of delay in anticoagulation and the correlation of delay in anticoagulation with poor outcome. Results:A total of 131 patients were included, their age was 40.07±15.11 years old, and 68 (51.91%) were male. Of these, 65 patients (49.62%) were in the early anticoagulation group and 14 (10.69%) were in the poor outcome group. Compared with the late anticoagulation group, the early anticoagulation group had a significantly higher proportion of patients with seizures and brain parenchymal damage as well as higher D-dimer levels on admission, while the proportion of patients with visual impairment/papilloedema was significantly lower (all P<0.05). Compared with the good outcome group, the poor outcome group had significantly higher proportions of patients with seizures, dyskinesia, impaired consciousness, low Glasgow Coma Scale score, and brain parenchymal damage as well as higher D-dimer, total cholesterol and low density lipoprotein cholesterol levels, sites of thrombus involvement were more common in the superior sagittal and straight sinuses, and significantly lower proportions of patients with headache and lower albumin levels on admission (all P<0.05). Multivariate logistic regression analysis showed that visual impairment/papilloedema (odds ratio [ OR] 0.119, 95% confidence interval [ CI] 0.030-0.473; P=0.002) and brain parenchymal damage ( OR 1.341, 95% CI 1.042-1.727; P=0.023) were independently associated with a delay in anticoagulation treatment, and a delay in anticoagulation treatment ( OR 6.102, 95% CI 1.185-30.504; P=0.030) and D-dimer level on admission ( OR 1.299, 95% CI 1.141-1.480; P<0.001) were the independent predictors of poor outcome in patients with CVST. Conclusions:Visual impairment/papilloedema and absence of brain parenchymal damage on cranial imaging are the independent risk factors for delay in anticoagulation in patients with CVST. The delay in anticoagulation is strongly associated with the poor outcome in patients with CVST.

Mitochondria is involved in many important physiological activities such as energy supply, signal transduction, cell differentiation, etc., and plays an significant role in the occurrence and development of diseases. Using mitochondria as a target is a new strategy for cancer treatment. The use of nanotechnology to construct a mitochondrial targeted nano-drug delivery system can improve the solubility of traditional drugs, prolong the half-life of drugs in the body, increase the bioavailability and concentration of drugs at the tumor site, and reduce the toxic and side effects of drugs. It is expected to solve the resistance in the process of tumor treatment. This review focuses on the field of cancer treatment. Firstly, it introduces the mechanism of mitochondrial targeted nano-drug delivery system for cancer treatment. Secondly, it outlines the design ideas, classification and application research of mitochondrial targeted nano-drug delivery systems in the past five years. Finally, it expands the analysis of other studies that target mitochondria, such as bionic vectors, and presents its advantages and disadvantages, which provide a basis for in-depth research on drug delivery systems in the future.

ObjectiveSepsis associated acute kidney injury （SA-AKI） is a critical clinical disease. The purpose of this study was to investigate the role and molecular mechanism of miR-4321 in the HK2 cellular damage induced by lipopolysaccharides （LPS）. MethodsRT-qPCR was conducted to detect the expression of miR-3165， miR-4270 and miR-4321 in LPS-induced HK2 cell model and cecal ligation and puncture （CLP）-induced renal injury model. In LPS-induced HK2 cell model， miR-4321-inhibitor was used to inhibit the miR-4321 expression. The effects of miR-4321 on cell proliferation， cell viability， cytokines and apoptosis-related protein levels were evaluated by CCK-8 analysis， EdU staining analysis and western blotting analysis， respectively. In CLP-induced renal injury model， miR-4321-Antago was used to intervene the miR-4321 expression. The changes of renal tissue structure were examined by H&E staining. The levels of serum creatinine and blood urea nitrogen （BUN） were measured by colorimetric method. ELISA was employed to assess the expression of interleukin-6 （IL-6）， interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in serum. IHC staining and western blotting were performed to determine the mTOR level and apoptosis-related protein expression in kidney tissues. Target genes of miR-4321 were predicted by Targetscan software and verified by dual-luciferase reporter assay. ResultsCompared with the control group， the miR-4321 expression was increased in LPS-induced HK2 cell model （n=3， t=7.154， P=0.001 3）. miR-4321 inhibitor promoted the proliferation and viability of HK2 cells， decreased the expression of LPS-induced IL-6， IL-1β and TNF-α and apoptosis-related proteins. In vivo experiments showed that miR-4321-Antago inhibited serum creatinine and BUN levels in CLP mice， improved renal injury， reduced levels of IL-1β， IL-6 and TNF-α， promoted the mTOR expression in renal tissues and inhibited the apoptosis-related protein expression. mTOR signaling pathway was believed the target gene of miR-4321. ConclusionInhibition of miR-4321 significantly alleviates SA-AKI， which may be achieved by increasing the expression of mTOR.

Achyranthes bidentata Blume is widely used as a traditional Chinese medicine with the effects of nourishing the liver and kidneys and strengthening muscles and bones. In this work, a rapid and simple strategy was developed for characterizing phytoecdysteroids by ultra-high-performance liquid chromatography coupled with liner ion trap-Orbitrap mass spectrometry using electrospray ionization in the negative mode. As a result, 47 phytoecdysteroids were unambiguously or tentatively characterized. Among them, seven known compounds were identified according to the reference standards along with molecular formula, retention time and fragmentation patterns, while others were mostly potential new compounds. Through targeted isolation, the structures of three new compounds were determined by NMR spectra, which were consistent with LC-MS characterization. The present study provides an efficient method to deeply characterize phytoecdysteroids.
Achyranthes/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Gas Chromatography-Mass Spectrometry ; Mass Spectrometry ; Medicine, Chinese Traditional ; Spectrometry, Mass, Electrospray Ionization/methods*