Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Objective: To explore the incidence and risk factors of cardiovascular events in hematological neoplasms patients treated with anthracyclines in the real world. Methods: A total of 408 patients with lymphoma and leukemia, who were treated with anthracyclines during hospitalization in the First Affiliated Hospital of Dalian Medical University from January 1, 2018 to July 31, 2021, were included in this retrospective study. Patients were divided into cardiovascular event group (n=74) and non-cardiovascular event group (n=334). The primary endpoint was cardiovascular events (arrhythmia, heart failure, acute myocardial infarction etc.) after anthracyclines therapy. The secondary endpoint was all-cause mortality, cardiovascular-cause death, discontinued chemotherapy due to cardiovascular events. Multivariate regression analysis was used to investigate the risk factors of cardiovascular events. Kaplan-Meier was performed to calculate the incidence of all-cause mortality. Results: The mean age was (55.6±14.9) years, and there were 227 male patients (55.6%) in this cohort. The median follow-up time was 45 months. During follow-up, cardiovascular adverse events occurred in 74 patients (18.1%), including 45 heart failure (38 were heart failure with preserved ejection fraction), 30 arrhythmia, 4 acute myocardial infarction and 2 myocarditis/pericarditis. Multivariate regression analysis showed age (OR=1.024, 95%CI 1.003-1.045, P=0.027) and history of hypertension over 10 years (OR=2.328, 95%CI 1.055-5.134, P=0.036) were independent risk factors for the cardiovascular events. Kaplan-Meier survival curve showed mortality was significantly higher in cardiovascular event group than in non-cardiovascular event group (47.3% vs. 26.6%, P=0.001). In the cardiovascular event group, chemotherapy was discontinued in 9 cases (12.2%) due to cardiovascular events and cardiovascular death occurred in 7 cases (9.5%). Conclusions: Although heart failure is the main cardiovascular event in lymphoma and leukemia patients post anthracyclines therapy, other cardiovascular events especially arrhythmias are also common. The presence of cardiovascular events is associated with higher risk of all-cause mortality in these patients. Age and long-term hypertension are independent risk factors for cardiovascular events in lymphoma and leukemia patients after anthracyclines treatment.
Humans ; Male ; Adult ; Middle Aged ; Aged ; Child ; Anthracyclines/adverse effects* ; Retrospective Studies ; Risk Factors ; Heart Failure/drug therapy* ; Myocardial Infarction/complications* ; Hematologic Neoplasms/complications* ; Arrhythmias, Cardiac/complications* ; Leukemia/complications* ; Hypertension/complications*

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Acquired Immunodeficiency Syndrome/prevention & control* ; China/epidemiology* ; Disease Outbreaks ; HIV Infections/prevention & control* ; Humans ; Prevalence

Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients. Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control. Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.

OBJECTIVE: To observe the clinical effect on spinal low back pain (SLBP) in Air Force crew treated with novel thumbtack needling therapy and to analyze the relevant factors of the therapeutic effect. METHODS: A total of 120 Air Force crew with SLBP were randomized into a thumbtack needling group (40 cases), an external treatment group (40 cases, 1 case dropped off ) and a combined treatment group (40 cases, 1 case dropped off ). In the thumbtack needling group, the thumbtack needling therapy was adopted. The novel thumbtack needles were inserted at the lower No.6 region of the wrist-ankle acupuncture, Yaotongdian (EX-UE 7), Yaoyangguan (GV 3), etc. Each point was pressed and kneaded for 1 min each time, 3 or 4 times a day. The treatment for 3 days was taken as one course. At the interval of 2 days, 3 courses were required totally. In the external treatment group, RESULTS: Compared with the values before treatment, McGill scores and ODI scores were reduced ( CONCLUSION The thumbtack needling therapy is significantly effective on spinal low back pain in Air Force crew and is of the safety. Hence, this therapy is applicable to be promoted in the primary care army hospital.
Acupuncture Points ; Acupuncture Therapy ; Electromyography ; Humans ; Low Back Pain/therapy* ; Needles ; Treatment Outcome

OBJECTIVETo observe wet cupping therapy (WCT) on local blood perfusion and analgesic effects in patients with nerve-root type cervical spondylosis (NT-CS).

METHODSFifty-seven NT-CS patients were randomly divided into WCT group and Jiaji acupoint-acupuncture (JA) group according a random number table. WCT group (30 cases) was treated with WCT for 10 min, and JA group (27 cases) was treated with acupuncture for 10 min. The treatment efficacies were evaluated with a Visual Analogue Scale (VAS). Blood perfusion at Dazhui (GV 14) and Jianjing (GB 21) acupoints (affected side) was observed with a laser speckle flowmetry, and its variations before and after treatment in both groups were compared as well.

RESULTSIn both groups, the VAS scores significantly decreased after the intervention (P<0.01), while the blood perfusion at the two acupoints significantly increased after intervention (P<0.05); however, the increasement magnitude caused by WCT was obvious compared with JA (P<0.05).

CONCLUSIONSWCT could improve analgesic effects in patients with NT-CS, which might be related to increasing local blood perfusion of acupunct points.

Objective To study the effect and mechanism of endoplamic reticulum stress on the auditory cortex injury after focal cerebral ischemia-reperfusion injury in rats.Methods 30 healthy male adult SD rats were chosen and randomly divided into 2 groups,ischemia-reperfusion(I/R) group and sham operated control,with each group 15 rats.The rats in I/R group were operated for suture-occluded method to establish middle cerebral artery occlusionmodel(MCAO),with ischemia for 60 mins followed by reperfusion for 24 h.And the control group was only to be isolated cervical vessels,with no thread embolism inserted.The auditory brainstem response (ABR) was tested before operation and at 24 h post-operation respectively.The neurological deficits,ratio of infarct volume were evaluated.The pathological changes were observed by HE.Neurocyte apoptosis were observed by Tunel,and the AI were determined.The expression of GRP78,Caspase-12 were detected by immunohistochemistry and Western blotting.Results Compared with the sham group,the neurological function scores,the infarct volume of brain of I/R group increased significantly.The threshold of ABR elevated significantly and AI rised in I/R group.HE staining showed that the neurons in the sham group were arranged in order,the shape was normal,but in the I/R group the normal structure disappeared,the nuclei were condensed.The expression of GRP78,Caspase-12 protein were significantly up-regulated.All of the differences above have statistical significance(P＜0.05).Conclusion The mechanism of hearing loss after focal cerebral ischemia-reperfusion injury in rats is perhaps related to endoplamic reticulum stress,and GRP78,Caspase-12 participate in the process of neuron apoptosis on auditory cortex caused by ERS.

Objective The pathogenesis of type 2 diabetes mellitus (DM) is complex and its molecular mechanism remains unclear. This study was to explore the effect of metformin on the TLR4/MyD88/NFκB signaling pathway in the skeletal muscle of type 2 DM rats and its anti-inflammation mechanism from the perspective of immune inflammation.Methods Forty SD male rats were equally randomized into four groups, normal diet, type 2 DM model, insulin treatment (DM+INS), and metformin treatment (DM+MET). The DM model was established in the latter three groups by feeding the rats on a diet of high fat and high glucose followed by intraperitoneal injection of STZ at 30 mg/kg at the end of the 8th week. After modeling, the animals of the DM+INS and DM+MET groups were treated by hypodermic injection of insulin at 1 IU/d and intragastrical administration of metformin at 200 mg/（d·kg） respectively for 4 weeks. Then, the Homeostasis Model Assessment-insulin resistance (HOMA-IR) was calculated, the content of serum IL-23 measured by ELISA, the expressions of AMPK, TLR4, MyD88 and NFκB in the skeletal muscle detected by Western blot, and the levels of MyD88 mRNA and TLR4 mRNA determined by RT-PCR.Results HOMA-IR was significantly elevated in the DM model, DM+INS and DM+MET groups as compared with that in the normal diet group (4.55±0.22, 4.32±0.32 and 1.79±0.15 vs 1.56±0.04, P<0.05), lower in the DM+MET than in either the DM model (P<0.05) or the DM+INS group (P<0.05). The content of serum IL-23 was also markedly increased in the DM model, DM+INS and DM+MET groups in comparison with that in the normal diet group (\[2.279±0.472\], \[1.886±0.233\] and \[1.205±0.398\] vs \[0.788±0.193\] μg/L, P<0.05), lower in the DM+MET than in either the DM model (P < 0.05) or the DM+INS group (P<0.05). A positive correlation was found between HOMA-IR and serum IL-23 in both the DM model (r=0.716, P<0.05) and the DM+MET group (r=0.725, P<0.05). The levels of TLR4 mRNA, MyD88 mRNA, TLR4, MyD88, and NFκB were all increased in the DM model, DM+INS and DM+MET groups compared with those in the normal diet group (P<0.05), lower in the DM+INS and DM+MET than in the DM model (P<0.05), and even lower in the DM+MET than in the DM+INS group (P<0.05). The expression of AMPK in the skeletal muscle was remarkably upregulated in the M+MET group as compared with the other three groups (P<0.05).Conclusion Metformin acts against inflammation and improves insulin resistance by activating AMPK, inhibiting the TLR4/MyD88/NFκB signaling pathway in the skeletal muscle and down-regulating the expression of IL-23.

Clinical application evaluation research of Guidelines for the Diagnosis and Treatment of Common Diseases of Pediatrics in Traditional Chinese Medicine intends to evaluate the quality level and clinical application of the guideline. A questionnaire and prospective case survey methods were used to evaluate the applicability evaluation based on the clinician questionnaire and the application evaluation based on clinical case observation. The applicability evaluation, familiarity and utilization rate of doctors' guidelines were 85.06%, 62.76%; Sort by technical grade, intermediate grade doctors have a higher familiarity rate and utilization rate, while the junior grade doctor's is lower; Guide quality level of applicability evaluation, other items' rational percentage are better than 96% except the items of health preserving and prevention and other treatment is relatively low; Items' applicable percentage of applicability evaluation are more than 91% except the item of guide simplicity. Comprehensive applicability evaluation, The percentage of the guideline applicable to clinical practice accounted for 94.94%. The consistency rate of syndrome differentiation and clinical application is more than 96% in addition to prescription medication, other treatments and health preserving and prevention of the guidelines apply consistency of application evaluation. The percentage of good treatment effect accounted for 92.96% of application effect evaluation. The safety percentage is 99.89% and economy is 97.45%. The research shows that of Guidelines for the Diagnosis and Treatment of Common Diseases of Pediatrics in Traditional Chinese Medicine quality level is good and is basically applicable to pediatric clinical practice which can be used as a standardized recommendation of pediatric common diseases' treatment specification. A small part of the guidelines are not applicable and need to be further consummated. Health preserving and prevention and other treatment of the guideline need to be revised.

The application of prostate-specific antigen (PSA) in the screening and diagnosis of prostate cancer (PCa) has improved the clinical management of PCa patients.However,the PSA assay has been faced with criticism due to its potential association with over-diagnosis and subsequent overtreatment of indolent patients.Matrix metalloproteinase-26 (MMP26) is a member of matrix metalloproteinases (MMPs) and has been reported to be highly expressed in many cancers.This investigation evaluated the potential of serum MMP26 as a biomarker for PCa.The level of serum MMP26 was measured by enzyme-linked immunosorbent assay (ELISA) in 160 subjects including PCa group (n=80),benign prostatic hyperplasia (BPH) group (n=40) and control group (n=40).Furthermore,we evaluated the expression of MMP26 in tissues by immunohistochemistry.The results showed the serum MMP26 levels were significantly higher in PCa group than in BPH group and control group.Similarly,the MMP26 protein was positive in PCa tissues and negative in BPH tissues and control tissues.In conclusion,these results suggested MMP26 could be used as a potential serum biomarker in the diagnosis of PCa.