Objective To study clinical features and mechanism in patients suffered from chronic hepatitis B achieving seroconversion of HBsAg by combination treatment with interferon (IFN) and nucleoside analogue (NA). Methods Thirty-two cases with chronic HBV hepatitis were enrolled into this retrospective study. All of them received combination treatment with IFN and Lamivudine/Adefovir, as well as achieved seroconversion of HBsAg from June, 2001 to May, 2007. All the cases in this study were followed up. Results Generally, serum HBV DNA fell below the detection limit 3 to 6 months after starting combination treatment. Virological breakthrough/relapse or new clinical resistant had not been found in all enrolments after combination treatment, including patients with previous resistant to Lamivudine, although the average length of treatment was over 2 years. The average period of following up after seroconversion of HBsAg was 13.2 months. Two cases transfered back to HBsAg positive, one of them achieved seroconversion of HBsAg again by the anti-virus treatment, and the other one gave up treatment and remained anti-HBe positive and HBeAg negative.The other 30 eases kept at the stage of seroconversion of HBsAg. Seven patients underwent liver biopsy after seroconversion of HBsAg, and 3 of them had taken liver biopsy before combination therapy too. Biopsy specimens were scored for fibrosis and neeroinflammation according to the Knodell histological activity index. Six cases showed HBsAg and HBcAg negative by immunohistochemistry,and only 1 case with HBsAg positive in liver tissue experienced relapse. Inflammation and fibrosis grade of the 3 cases who had taken liver biopsy twice were lowered after HBsAg seroconversion,although the ALT level of 1 case who had turned from G2S4 to GIS2-3 remained abnormal after HBsAg seroconversion. According to the sequence and character of HBsAg seroconversion, there were three models of HBsAg conversion. The sequence of transition was HBV DNA→HBeAg→HBsAg,which was dominant one, accounting for 59%(19/32 cases). HBV DNA negative, and the titer of HBeAg wandering at a low level, after then HBeAg and HBsAg change to negative in the same time,31% (10/32 cases). The titer of HBsAg decreased rapidly after the HBV DNA clearance, and the HBsAg clearance was earlier than HBeAg, 9% (3/32 cases). After 1 year of combination therapy,there were 15 of 21 cases (71.4%) whose titer HBsAg showed less than 100 COI by agent from Roche, and 7 of 11 cases (63.6%) whose titer HBsAg showed less than 250 IU/L by agent from Abbott. The frequency of adverse reaction was similar with that induced by IFN monotherapy, and no new adverse reaction was found. Conclusions Combination therapy and long course treatment might be the key to achieve the HBsAg seroconversion. Those with HBsAg in liver tissue and (or) low serum anti-HBs are more likely to relapse. The titer of HbsAg<100 COI (Roche, Germany) or<250 IU/L (Abbott, USA) after one year treatment may be regarded as a predict index of HBsAg seroconversion.

Objective To observe the effect of hypoxia on the expression of epithelial growth factor receptor (EGFR) and cell apoptosis of breast and cervical cancer xenografts in nude mouse models.Methods The nude mouse models with MCF-7 and HeLa xenografts were established.The degree of hypoxia and EGFR expression were observed by confocal microscopy.The influence of EGFR expression on cell apoptosis under hypoxia was observed by TUNEL assay.Results EGFR expression was either up-regulated or down-regulated in the MCF-7 and HeLa cells with high degree of hypoxia.Furthermore,the degree of apoptosis was reduced in tumor tissues with high EGFR expression compared with that in those with low expression of EGFR.Conclusion The hypoxia in MCF-7 and HeLa cells exerts heterogeneous effect on EGFR expression.Under hypoxic conditions,EGFR exoression is negatively correlated with cell apoptosis.

Objective To observe the recovery of superficial sensation and movement of lower limbs,the first urination and exhaust of patients after knee arthroscopy under spinal anesthesia.Methods Sev-enty-two patients undergoing arthroscopic knee surgery under subarachnoid anesthesia in the Sports Medicine Department of a class-3 grade-A hospital in Beijing between May and November 2020 were selected,including 56 males and 16 females,ranging in age from 13 to 59.The recovery time of su-perficial sensation and movement,first urination and exhaust were observed and recorded respectively.Then,the correlation of the above indexes to gender,age,weight,operation duration,tourniquet time and anesthesia time was analyzed.Results The patients regained their superficial feeling and lower limbs mobility 333.40±115.04 and 263.13±84.48 min after the anesthesia,with the recovery of the lower limbs movement 100 minutes earlier than the superficial feeling.Moreover,the first urina-tion and exhaust time were 358.33±111.78 min and 354.51±130.16 min after the lumbar anesthe-sia,respectively.In addition,the superficial feeling,lower limbs mobility and first urination of the males were 352.05±115.18 min,274.55±84.77 min and 376.43±113.25 min after the anesthe-sia,significantly later than the females(268.13±90.29 min,t=2.684,P=0.009;223.13±72.36 min,t=2.205,P=0.031;295.00±81.34 min,t=2.679,P=0.009).However,no significant differences were found between different sexes in their first exhaust(P>0.05).Moreover,superficial sense and motion re-covery were not correlated with the age and weight,as well as the durationof surgery,hemostatic band application and anesthesia(P>0.05).Conclusion The motion recovery after knee arthroscopy under subarachnoid anesthesia is earlier than the superficial sensation,followed by the first urination and first exhaust.Female patients regain their superficial sensation,movement and the first urination about 4～6 hours after anesthesia,earlier than males as they do about 6～8 hours after it.

AIM:To investigate the impact and regulatory mechanisms of zinc finger protein 36-like protein 1(ZFP36L1)on pancreatic carcinoma cell growth.METHODS:The ZFP36L1 expression in pancreatic carcinoma and its correlation with patient prognosis were analyzed using online databases UALCAN and GEPIA.Western blot was utilized to detect ZFP36L1 protein expression in pancreatic ductal cells(HPNE)and three different pancreatic carcinoma cell lines.CCK-8 and cell colony formation assays were performed to evaluate the effects of ZFP36L1 on pancreatic cancer cell prolif-eration.Wound healing and Transwell assays were used to assess the impact of ZFP36L1 expression changes on pancreatic carcinoma cell migration and invasion.Flow cytometry experiments were used to analyze the effect of ZFP36L1 on the pan-creatic carcinoma cell cycle process.Bioinformatics analysis was conducted to predict potential ZFP36L1 interacting pro-teins.Co-immunoprecipitation experiments were carried out to confirm the interaction between ZFP36L1 and mitogen-acti-vated protein kinase 14(MAPK14).Rescue experiments were performed to assess the function of MAPK14 in ZFP36L1-regulated pancreatic carcinoma cell growth.RESULTS:(1)ZFP36L1 is highly expressed in pancreatic carcinoma and is positively correlated with poor prognosis in pancreatic carcinoma patients.Compared to HPNE,ZFP36L1 is highly ex-pressed in MIA PaCa-2 and ASPC-1 cells,but relatively low in PANC-1 cells.(2)ZFP36L1 overexpression significantly increased the cell viability,colony formation,migration,and invasion abilities of PANC-1 and MIA PaCa-2 cells,while siRNA interference of ZFP36L1 led to opposite results.(3)ZFP36L1 promotes the entry of pancreatic carcinoma cells into the S phase of the cell cycle.(4)ZFP36L1 interacts with MAPK14 to regulate pancreatic cancer cell growth.MAPK14 overexpression reversed the cell viability and migration abilities of pancreatic carcinoma cells overexpressing ZFP36L1.Furthermore,it also decreased the cell viability and migration abilities of pancreatic carcinoma cells with ZFP36L1 inter-ference.CONCLUSION:ZFP36L1 is a potential oncogene in pancreatic carcinoma growth and may regulate pancreatic carcinoma cell growth through cell cycle modulation and interaction with MAPK14.

Objective:To investigated the expression and localization of the long non-coding RNA(lncRNA)STAG3L5P in oral squamous cell carcinoma(OSCC)cells and its effects on OSCC cell proliferation and migration.Methods:STAG3L5P expression in HNSC and OSCC was ana-lyzed online using gene expression profiling interactive analysis 2(GEPIA2)and the University of California Santa Cruz Xena(UCSC Xena)database,respectively.STAG3L5P expression in OSCC cell lines was detected using real-time fluorescence quantitative PCR(qPCR).Nuclear-cytoplasmic RNA fractionation assays were carried out to pinpoint the location of STAG3L5P.Cell counting kit-8(CCK-8)and Transwell migra-tion assays were used to assess OSCC cell proliferation and migration changes.The effect of STAG3L5P overexpression on epithelial-mesen-chymal transition(EMT)related gene expression was detected by qPCR and Western blot.The effect of STAG3L5P overexpression on PI3K/AKT pathway activity was also assessed by Western blot.Results:STAG3L5P was highly expressed in OSCC,and its expression correl-ated significantly with histological grade.STAG3L5P expression was significantly higher in OSCC cell lines than in normal cells.The level of cytoplasmic STAG3L5P in OSCC cells was significantly higher than that in the nucleus.The proliferation and migration capacity of OSCC cells overexpressing STAG3L5P were significantly enhanced compared to negative control OSCC cells.N-cadherin and vimentin mRNA and protein levels were significantly increased by STAG3L5P overexpression,while E-cadherin protein expression was decreased.Overexpression of STAG3L5P also increased activity of p-PI3K and p-AKT.Conclusions:STAG3L5P is up-regulated in OSCC,and STAG3L5P overexpression can promote OSCC cell proliferation and migration.This effect may be related to activation of the PI3K/AKT pathway,thus promoting EMT.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Background and purpose:Long noncoding RNA(lncRNA)can regulate gene transcription,mRNA shear,stabilization and translation,and it is an important regulatory factor in a variety of biological processes.This study aimed to investigate the expression and clinical features of lncRNA FLJ30679 in oral squamous cell carcinoma(OSCC)and its effect on the malignant biological behavior of OSCC.Methods:The expression of FLJ30679 in head and neck squamous cell carcinoma(HNSCC)tissues and normal tissues was analyzed by the UCSC Xena database for expression and prognosis.The expression of FLJ30679 in OSCC cell lines was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).The subcellular localization of FLJ30679 in OSCC cells was detected by RNA nuclear-cytoplasmic fractionation assays.FLJ30679 Smart Silencer was used to establish the FLJ30679 knockdown group(SS-FLJ30679),and overexpression plasmid of FLJ30679 was used to establish FLJ30679 overexpression group(FLJ30679).The effects of altered FLJ30679 expression on the proliferative and migration capacity of OSCC cells were examined by cell counting kit-8(CCK-8)and transwell migration assays.RTFQ-PCR and Western blot were used to determine the effect of altered FLJ30679 expression on the expression of epithelial-mesenchymal transition(EMT)-related genes in OSCC cells.The effects of altered FLJ30679 expression on the phosphoinositide 3-kinase(PI3K)/protein kinase(AKT)pathway were detected by Western blot.Results:Online query of database showed that FLJ30679 expression was higher in HNSCC tissues compared to normal tissues(P＜0.01).HNSCC patients with higher FLJ30679 expression had lower overall survival(P＜0.01).The RTFQ-PCR results showed that FLJ30679 was expressed at a higher level in six OSCC cell lines compared with normal cells,and was predominantly localized in the nucleus.The ability of OSCC cells in the SS-FLJ30679 group to proliferate and migrate was significantly lower compared with the SS-NC group(P＜0.01).OSCC cells in the FLJ30679 overexpression group had significantly higher proliferative and migratory capacities than those in the vector group(P＜0.001).RTFQ-PCR and Western blot results showed that FLJ30679 knockdown resulted in upregulation of mRNA and protein expression levels of E-cadherin(P＜0.01)and downregulation of mRNA and protein expression levels of N-cadherin and vimentin(P＜0.01).FLJ30679 overexpression resulted in downregulation of protein expression levels of E-cadherin(P＜0.01)and upregulation of mRNA and protein expression levels of N-cadherin and vimentin(P＜0.05).Western blot results showed that knockdown of FLJ30679 resulted in decreased protein expression levels of phosphorylated-PI3K(p-PI3K)and phosphorylated-AKT(p-AKT)(P＜0.001),and overexpression of FLJ30679 resulted in increased protein expression levels of p-PI3K and p-AKT(P＜0.01).Conclusion:The expression of FLJ30679 was increased in OSCC tissues and cells.It promoted the proliferation and migration ability of OSCC cells,which may be caused by FLJ30679 promoting EMT via PI3K/AKT pathway.

Objective:To explore the association between frailty index (FI) and the risk for cardiovascular disease (CVD) in adults in Inner Mongolia Autonomous Region, and provide new evidence for the prevention of CVD in adults in Inner Mongolia Autonomous Region.Methods:The FI was constructed by using the data from a prospective cohort with a sample size of 25 055 individuals in 6 years of follow-up, and the prevalence of frailty in adults in Inner Mongolia Autonomous Region was described by the FI, and Cox proportional hazard regression model was used to evaluate the association between the FI and the incidence of CVD in adults in Inner Mongolia Autonomous Region.Results:The FI of the study population was 0.24±0.09. The population in the pre-frail (FI: 0.21-0.27) and frail (FI≥0.28) phases had increased risk for CVD compared to non-frail (FI≤0.20) population [pre-frail: hazard ratio ( HR)=1.232, 95% CI: 1.127-1.347; frail phase: HR=1.418, 95% CI:1.299-1.548]. For every 0.10 increase in FI, the risk for cardiovascular disease increased by 20.3% ( HR=1.203,95% CI:1.156-1.252). Conclusions:In this study, we constructed a FI, which can suggest the risk for CVD. As the increase of frailty degree, the risk for CVD increases.

Energy metabolism reconstruction is the new target of the treatment of heart failure. By combing the researches of Chinese medicinals for energy metabolism reconstruction of heart failure， it was found that Chinese medicinal compound formula and single Chinese medicinal have a certain role in regulating energy metabolism， mainly through three aspects， including the optimization of substrate utilization， improvement of mitochondrial structure， function， and homeostasis， and improvement of mitochondrial energy transport， so as to make the energy metabolism of the cardiomyocyte adjusted in the direction of beneficial to the organism， increasing the supply of energy， and improving the cardiac function.

Severe pneumonia is one of the most common and critical respiratory diseases in clinical practice. It is characterized by rapid progression， difficult treatment， high mortality， and many complications， posing a significant threat to the life and health of patients. The pathogenesis of severe pneumonia is highly complex， and studies have shown that its occurrence and development are closely related to multiple signaling pathways. Currently， the treatment of severe pneumonia mainly focuses on anti-infection， mechanical ventilation， and glucocorticoids， but clinical outcomes are often not ideal. Therefore， finding safe and effective alternative therapies is particularly important. In recent years， with the deepening of research into traditional Chinese medicine （TCM）， it has gained widespread attention in the treatment of severe pneumonia. This paper reviewed the relationship between severe pneumonia and relevant signaling pathways in recent years and how TCM regulated these pathways in the treatment of severe pneumonia. It was found that TCM could regulate the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， NOD-like receptor protein 3 （NLRP3）， and nuclear factor E₂-related factor 2 （Nrf2） signaling pathways， playing a role in reducing the inflammatory response， inhibiting cell apoptosis and pyroptosis， improving oxidative stress， and other effects in the treatment of severe pneumonia. Among these pathways， it was found that all of them regulated inflammation to treat severe pneumonia. Therefore， reducing inflammation is the core mechanism by which Chinese medicine treats severe pneumonia. This review provides direction for the clinical treatment of severe pneumonia and offers a scientific basis for the research and development of new drugs.