Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

BACKGROUND:Intervertebral disc degeneration is an important cause of low back pain.At present,there are many modeling methods for disc degeneration in China and abroad,but there is not a model for low back pain due to disc degeneration. OBJECTIVE:To compare the effect of mechanical puncture combined with tumor necrosis factor α and complete Freund's adjuvant with a conventional disc mechanical puncture alone. METHODS:A total of 18 male adult Sprague-Dawley rats were randomly divided into 3 groups,with 6 animals in each group.No treatment was given in the blank group.Animal models of intervertebral disc degeneration were made in the L4-5 segments of rats in the control using conventional mechanical puncture.In the experimental group,on the basis of mechanical puncture,tumor necrosis factor α+complete Freund's adjuvant was injected into the L4-5 intervertebral discs using a microinjector to establish a model of disc degeneration induced by mechanical puncture combined with inflammatory factors.Four weeks after surgery,the pain threshold of rats was measured by the hot plate method for assessing the perception of heat injury in rats with intervertebral disc degeneration.MRI examination was performed to observe the disc degeneration in each group.ELISA was used to detect the levels of serum tumor necrosis factor α,interleukin 1β,interleukin 6 and prostaglandin E2.Hematoxylin-eosin and Safranin O-fast green staining were used to observe the morphological changes of the disc. RESULTS AND CONCLUSION:In terms of pain,the behavioral pain threshold of the experimental group was continuously decreased,and the levels of serum inflammatory factors were significantly higher compared with the control group.In terms of morphology,the MRI results showed that the L4-5 nucleus pulposus signal completely disappeared in the experimental group.Histopathological results showed that in the control group,the nucleus pulposus was intact,more notochord cells were visible,and some fiber rings were ruptured,while in the experimental group,there are fewer notochord cells and the structure of the nucleus pulposus and fibrous ring is disturbed,with the boundary disappearing.To conclude,mechanical puncture combined with tumor necrosis factor alpha and complete Freund's adjuvant can successfully establish a discogenic low back pain model in rats.This operation is simple and economical to achieve obvious disc degeneration and low back pain,with greatly shortened molding cycle.This model can be used as a reference for studying discogenic low back pain models.

Objective:To construct a risk prediction model for the inter-hospital transfer of critically ill children using machine learning methods, identify key medical features affecting transfer outcomes, and improve the success rate of transfers.Methods:A prospective study was conducted on critically ill children admitted to the pediatric transfer center of Hunan Children's Hospital from January 2020 to January 2021. Medical data on critical care features and relevant data from the Pediatric Risk of Mortality (PRISMⅢ) scoring system were collected and processed. Three machine learning models, including logistic regression, decision tree, and Relief algorithm, were used to construct the risk prediction model. A back propagation neural network was employed to build a referral outcome prediction model to verify and analyze the selected medical features from the risk prediction model, exploring the key medical features influencing inter-hospital transfer risk.Results:Among the 549 transferred children included in the study, 222 were neonates (40.44%) and 327 were non-neonates (59.56%). There were 50 children in-hospital deaths, resulting in a mortality rate of 9.11%. After processing 151 critical care medical feature data points, each model selected the top 15 important features influencing transfer outcomes, with a total of 34 selected features. The decision tree model had an overlap of 72.7% with PRISMⅢ indicators, higher than logistic regression (36.4%) and Relief algorithm (27.3%). The training prediction accuracy of the decision tree model was 0.94, higher than the accuracy of 0.90 when including all features, indicating its clinical utility. Among the top 15 important features selected by the decision tree model, the impact on transfer outcomes was ranked as follows based on quantitative feature violin plots: base excess, total bilirubin, ionized calcium, total time, arterial oxygen pressure, blood parameters (including white blood cells, platelets, prothrombin time/activated partial thromboplastin time), carbon dioxide pressure, blood glucose, systolic blood pressure, heart rate, organ failure, lactate, capillary refill time, temperature, and cyanosis. Eight of these important features overlapped with PRISMⅢ indicators, including systolic blood pressure, heart rate, temperature, pupillary reflex, consciousness, acidosis, arterial oxygen pressure, carbon dioxide pressure, blood parameters, and blood glucose. The decision tree was used to select the top 15 medical features with high impact on the neonatal and non-neonatal datasets, respectively. A total of 19 features were selected, among which there were 8 differences and 11 overlap terms between the important features of the neonatal and non-neonatal.Conclusions:Machine learning models could serve as reliable tools for predicting the risk of inter-hospital transfer of critically ill children. The decision tree model exhibits superior performance and helps identify key medical features affecting inter-hospital transfer risk, thereby improving the success rate of inter-hospital transfers for critically ill children.

Objective To investigate whether embolization surgery can improve mid-to-long-term outcomes related to quality of life,anxiety and depression in patients with unruptured intracranial aneurysms(UIA).Methods This prospective study included patients diagnosed with UIA within 30 days.Patients were divided into two groups based on treatment:the embolization group and the conservative group.The assessments of quality of life,depression,and anxiety were conducted using the medical outcome study short form-36(SF-36),self-rating depression scale(SDS),and self-rating anxiety scale(SAS)at baseline,3 months,and 5 years after treatment.In the embolization group,psychological trauma was assessed using the impact of event scale-revised(IES-R)at 3 months and 5 years post-surgery.Results A total of 113 patients were involved in the analysis including 76 in the embolization group and 37 in the conservative group.Compared to the conservative group,SF-36 data showed that the embolization group had a lower physical function(80.3±16.4 vs.86.1±12.8,P=0.046)and role-physical(47.37±43.32 vs.67.57±34.29,P=0.015)scores at 3 months,but a higher mental health score(68.16±18.80 vs.61.62±14.62,P=0.048).At 5 years,all dimensions of SF-36 improved significantly compared to baseline(all P<0.05).The SDS and SAS scores in the embolization group were significantly lower at both 3 months and 5 years compared to baseline(both P<0.05).The decrease in SDS(-2.8±10.6 vs.0.5±6.5)and SAS(-2.7±11.8 vs.1.2±5.4)scores in the embolization group at 3 months was greater than in the conservative group(both P<0.05).Subgroup analysis showed that patients with depression or anxiety at baseline in the embolization group experienced a significant decrease in SDS and SAS scores at 3 months and 5 years compared to baseline(both P<0.05).Additionally,in the embolization group,the IES-R score at 3 months was 37.5±13.8,which was significantly higher than the critical threshold(P=0.005),but decreased to 33.8±13.3 at 5 years post-surgery.Conclusions Patients with unruptured intracranial aneurysms experienced long-term improvements in quality of life after embolization surgery.Embolization surgery also helped alleviate depression and anxiety.

AIM To explore the effects of praeruptorin A from Suhuang antitussive capsules on cough variant asthma(CVA).METHODS The rats were randomly divided into the normal group,the model group,the dexamethasone group(0.5 mg/kg),the Suhuang antitussive capsules group(7 g/kg)and the low,medium and high dose praeruptorin A groups(15,30 and 60 mg/kg).The rat model of CVA was established by intraperitoneal injection of sensitizer(1 mg/mL ovalbumin and 10 mg/mL aluminum hydroxide)and aerosol inhalation of 1%ovalbumin followed by the corresponding dosing of drugs by gavage initiated on the 14th day.Another 14 days later,the rats had their pathological pulmonary changes observed by HE,Masson and PAS stainings;their number of inflammatory cells in bronchoalveolar lavage fluid(BALF)detected by hematology analyzer;and their levels of IL-4,IL-5,IL-13 and MUC5AC in BALF detected by ELISA.The RAW264.7 cell inflammatory model induced by lipopolysaccharide(LPS)was treated with 4,8,16 μmol/L praeruptorin A or 0.25 mg/mL Suhuang antitussive capsules,respectively.And the cells had their NO level detected by Griess method,and their ROS expression observed using fluorescence microscopy.The detections of the pulmonary and cellular mRNA expressions of IL-6,IL-1β,COX-2,iNOS and PPAR-γ by RT-qPCR;and the protein expressions of p-P65,P65,p-IκBα,IκBα,NLRP3,caspase-1(p20)and IL-1β by Western blot were conducted in both the cells and the rats.RESULTS The in vivo result showed that praeruptorin A reduced the cough frequency(P＜0.01);prolonged the cough latency(P＜0.05,P＜0.01);reduced the number of eosinophils and neutrophils in BALF(P＜0.05,P＜0.01);decreased the levels of IL-4,IL-5,IL-13 and MUC5AC in BALF and the pulmonary mRNA expressions of IL-6,IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);and decreased the phosphorylation of P65 and IκBα protein and NLRP3,caspase-1(p20)and IL-1β protein expressions(P＜0.05,P＜0.01)as well.The in vitro result showed that praeruptorin A inhibited the release of LPS-induced NO and reduce the ROS level(P＜0.01);decreased the mRNA expressions of IL-1β,COX-2 and iNOS(P＜0.05,P＜0.01);increased PPAR-γ mRNA expression(P＜0.05),and decreased the phosphorylation of P65 and IκBα protein and the expression of NLRP3 protein(P＜0.05,P＜0.01).CONCLUSION Praeruptorin A,one of the main antitussive components of Suhuang antitussive capsules,may improve CVA because of its anti-inflammatory and antitussive role by inhibiting the activation of NF-κB signaling pathway and reducing the expression of NLRP3 inflammatory corpuscles.

Aim To investigate the role of mitochondrial translocator protein(TSPO)in the apoptosis of HepG2 cells induced by tanshinone IIA(Tan II A)and the involved mechanism. Methods Following the HepG2 cells treated with Tan ⅡA at 2.5, 5 and 10 μmol·L-1, the cell viability was determined by MTT assay, and intracellular ATP content was determined by luciferin-luciferase method. Oxygen utilization was measured polarographically with a Clark oxygen electrode. Cell apoptosis was determined by Hoechst 33342 staining and flow cytometry. The mitochondrial membrane potential was assessed with JC-1 staining. The intracellular distribution of TSPO was examined by TSPO immunostaining, and the expressions of TSPO, Cyto C, caspase-3, caspase-9 were determined by immunoblotting analysis. Results Tan II A inhibited the proliferation of HepG2 cells in a dose-and time-dependent manner. The treatment with Tan II A inhibited ATP production and oxygen utilization of mitochondria. In addition, Tan ⅡA enhanced TSPO expression and accumulation in nuclei and up-regulated the expression of Cyto C, caspase-3 and caspase-9. Conclusions Tan II A induces the apoptosis of HepG2 cells, which may be related to the TSPO-mediated mitochondrial dysfunction.

Objective To explore the effect of JianpiYiqi Decoction on the proliferation,invasion and apoptosis of Human hepatoma Huh-7 cells under the constructed inflammatory microenvironment stimulated by lipopolysaccharide(LPS)and adenosine triphosphate(ATP),and to detect the interleukin-1β(IL-1β)and interleukin-18(IL-18)Expression level in cells.Methods Construction drug-containing serum of JianpiYiqi.Adopt LPS and ATP were added to the cell culture medium to stimulate hepatoma cells and construct the inflammatory microenvironment.The cells were divided into blank group,model group,VX-765 group(10 μmol·L-1),low concentration of traditional Chinese medicine group(15%JianpiYiqi Decoction low dosedrug-containing serum),Medium concentration of traditional Chinese medicine group(15%JianpiYiqi Decoction Medium dose drug-containing serum),and high concentration of traditional Chinese medicine group(15%JianpiYiqi Decoction high dose drug-containing serum).Adopt CCK-8 method was used to detect the proliferation level of cells in each group after cell intervention;The apoptosis rate of cells in each group was detected by Annexin V-FITC/PI method;Adopt Transwell method was used to detect the level of cell invasion in each group;adopt PI single staining was used to detect the cell cycle level in each group;Adopt ELISA method and Western blot method were used to detection of IL-1β and 1l-18 expression level in Huh-7 cells.Results Compared with the blank group,in the model group stimulated by LPS and ATP,the proliferation level,invasion level,IL-1β and IL-18 expression level of Huh-7 cells were higher(P<0.05),and the apoptosis level was lower(P<0.05).Compared with other groups,the Medium concentration of traditional Chinese medicine group and the high concentration of traditional Chinese medicine group could effectively inhibit the proliferation and invasion level of Huh-7 cells,block the cell proliferation cycle,reduce the cell survival rate(P<0.05),significantly induce apoptosis of Huh-7 cells(P<0.05),and reduce the expression levels of IL-1β and IL-18 in Huh-7 cells(P<0.05).Conclusion The drug-containing serum JianpiYiqi.The medium and high concentrations of JianpiYiqi Decoction drug-containing serum can inhibit the proliferation and invasion,block the cell cycle and induce apoptosis of human liver cancer Huh-7 cells by improving the inflammatory microenvironment in liver cancer Huh-7 cells.Its mechanism may be related to the inhibition of liver cancer cells.Analyze the levels of inflammatory factors IL-1β and IL-18 to achieve the therapeutic purpose of primary liver cancer.

Objective To explore the obstacles in palliative care consultation services and put forward the suggestions for improving the services in grade A tertiary hospitals. Methods A semi-structured interview was conducted with 17 medical workers who had requested palliative care consultation services in Peking Union Medical College Hospital. Results The palliative care consultation services were hindered by five obstacle factors including insufficient knowledge of patients and their families about palliative care,unsound understanding of medical workers about palliative care,poor implementation of consultation opinions,limited labor of palliative care team,and poor economic benefits from palliative care.In view of such obstacles,the following suggestions were put forward,which included increasing the acceptance of palliative care by patients and their families,enriching the knowledge of medical staff on palliative care,establishing a new cooperation model between consultation team and medical staff,strengthening the institutional guarantee for the development of palliative care,and establishing and perfecting the laws and policies related to palliative care. Conclusion Although there are many difficulties in the in-hospital palliative care consultation services in grade A tertiary hospitals,the demand and expectation of medical staff for palliative care are still increasing.
Humans ; Palliative Care ; Tertiary Care Centers ; Referral and Consultation ; Hospitalization

The clinical randomized controlled trial(RCT) of Chinese patent medicine in the treatment of influenza were reviewed and analyzed to provide basic information for clinical decision and related research. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, and Cochrane Library were searched for RCTs of Chinese patent medicine for influenza published from database inception to July 25, 2021. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. Ninety-two RCTs of Chinese patent medicine for influenza published between 2005 and 2021, were included, among which 17 RCTs(18.48%) had a sample size higher than 200 and the average sample size was about 145. Twenty-seven Chinese patent medicines were involved, including twenty-one oral medicines and six injections. The Chinese patent medicines in trials reported in more than five papers included Lianhua Qingwen Capsules/Gra-nules, Tanreqing Injection, and Reduning Injection. Fourteen intervention protocols were reported, of which Chinese patent medicine+western medicine+conventional treatment vs western medicine+conventional treatment(20.65%) was the most frequently employed. Additionally, 85.87% of the RCTs reported the course of treatment, and 80.43% of the RCTs determined 3-7 d as the intervention course. Forty-five outcome indicators were extracted, which were used 434 times, including symptoms/signs, physicochemical detection, safety events, TCM symptoms/syndromes, quality of life, long-term prognosis, and economic evaluation. Symptoms/signs(61.52%) exhibited the highest frequency. Methodological problems were prevalent in the included trials. The findings reveal that there are few clinical trials on influenza treatment by Chinese patent medicine, and the methodological problems are prominent, affec-ting the reliability and practicability of the trials. In the future research, the value characteristics of Chinese patent medicine should be highlighted and the quality control in the whole process should be strengthened based on the scientific and rigorous design.
China ; Clinical Trials as Topic ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Influenza, Human/drug therapy* ; Medicine, Chinese Traditional ; Nonprescription Drugs/therapeutic use* ; Quality of Life ; Reproducibility of Results

The present study reviewed the clinical randomized controlled trials(RCTs) of Chinese patent medicine for pneumonia to provide references for clinical research, guideline development, and policy formulation, and promote the quality improvement of clinical evidence. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, SinoMed were searched for RCTs of Chinese patent medicine for pneumonia from database inception to December 31, 2019. A total of 1 245 RCTs were included, involving 84 Chinese patent medicines, including 45 oral medicines and 39 injections. Specifically, 85.9% of RCTs had treatment course not exceeding 14 d; 43.3% of RCTs had a sample size of more than 100 cases and 6.1% of RCTs more than 200 cases; 13 types of interventions/controls were included in the RCTs, with Chinese patent medicine + western medicine vs western medicine as the top one used(32.6%). In outcome indicators, symptoms/signs(3 285) and physicochemical detection(2 066) were the most frequently applied. In the methodological evaluation, "allocation concealment" was not clearly described or mentioned in 71.2% of RCTs, and "blinding" in 23.9% of RCTs met the normative standards. Registration and research ethics were not clearly reported. There are many methodological deficiencies in terms of design and implementation in included RCTs, which may impact the reliability and practicability of the results of RCTs. Additionally, key standards were unclear(such as disease classification methods and selection of core outcome indicators). In conclusion, RCTs should give priority to the preciseness and scientificity of the protocol, strengthening quality control of the processes and accelerating the standardized research of key links.
China ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Pneumonia/drug therapy* ; Randomized Controlled Trials as Topic ; Reproducibility of Results