Traditionally, liver cirrhosis has a bleeding tendency due to the reduction in blood coagulation factors, hyperfibrinolysis, thrombocytopenia, and increased portal hypertension. Some studies show that the patients with live cirrhosis are in a state of hypercoagulability and tend to develop venous thromboembolism, which greatly affects the patients′ prognosis. This article reviews the epidemiological features and risk factors of venous thromboembolism, as well as the significance of prevention of venous thromboembolism in patients with liver cirrhosis, so as to guide clinical practice.

Objective:To observe the effects of kidney-tonifying and mind-calming acupuncture therapy on sleep,mood,sex hormone levels,and traditional Chinese medicine(TCM)symptoms in patients with perimenopausal insomnia(PMI). Methods:A total of 90 patients with PMI were randomly divided into a treatment group and a control group,with 45 cases in each group.Patients in the treatment group were treated with acupuncture at Shenshu(BL23),Taixi(KI3),Baihui(GV20),and Anmian(Extra).The control group was treated with sham acupuncture.Both groups were treated 3 times a week for 4 weeks.Pittsburgh sleep quality index(PSQI)and insomnia severity index(ISI)were used to evaluate the sleep quality of the subjects before treatment,after treatment,and 1 month after treatment(follow-up).Beck depression inventory(BDI)and Beck anxiety inventory(BAI)were used to evaluate the depression and anxiety of the subjects before treatment,after treatment,and at 1-month follow-up.The TCM symptom scale was used to evaluate the TCM symptoms of the subjects before treatment,after treatment,and 1 month after treatment.Serum levels of estradiol(E2),follicle-stimulating hormone(FSH),and luteinizing hormone(LH)were measured before and after treatment. Results:During the study,2 cases dropped out of the treatment group,and no cases dropped out of the control group.The PSQI scores of the treatment group were significantly lower after treatment and at 1-month follow-up compared with those before treatment(P<0.05),and the difference was statistically significant compared with that of the control group(P<0.05).In the control group,the PSQI score was significantly lower after treatment compared with before treatment(P<0.05),and the difference was not statistically significant at 1-month follow-up compared with before treatment(P>0.05).Compared with the pre-treatment,the ISI,BDI,BAI,and TCM symptom scale scores of the treatment group were lower after treatment and at 1-month follow-up(P<0.05),and the differences with the control group at the same time point were statistically significant(P<0.05).The differences in ISI,BDI,BAI,and TCM symptom scale scores of the control group before treatment,after treatment,and at 1-month follow-up were not statistically significant(P>0.05).After treatment,the serum E2 level in the treatment group was significantly higher than that before treatment(P<0.05),and the difference with the control group was statistically significant(P<0.05).The difference in the serum E2 level before and after treatment in the control group was not statistically significant(P>0.05).The differences in the serum FSH and LH levels between before and after treatment were not statistically significant in either group of subjects(P>0.05). Conclusion:Kidney-tonifying and mind-calming acupuncture therapy can improve sleep quality,relieve anxiety and depression,delay the decrease of serum E2 level,and improve related TCM symptoms in patients with PMI.

Objective This study aimed to investigate the effect of Dapagliflozin on the hypertrophy and apoptosis of cardiomyocytes induced by angiotensinⅡ(Ang Ⅱ).Methods Primary rat neonatal cardiomyocytes were isolated,cultured and randomly divided into 4 groups:control group,Ang Ⅱ group,dapagliflozin group 1(0.5 μmol/L),and dapagliflozin group 2(2 μmol/L).α-actin staining was used to detect cell area.qPCR was applied to detect embryonic gene transcription.Tunel staining was adopted to detect cell apoptosis level.The caspase3 kit was used to detect caspase3 activityand western blotting was used to detect classical signal molecules.Results The cell surface area of the Ang Ⅱ group was significantly larger than that of the control group(P＜0.05).The cell surface area of the dapagliflozin group 1 and the dapagliflozin group 2 was significantly lower than that of the Ang Ⅱ group(P＜0.05).The results of qPCR showed that the fetal gene transcription of Ang Ⅱ group was sig-nificantly higher than that of the control group(P＜0.05);the fetal gene transcription of dapagliflozin group 1 and dapagliflozin group 2 was lower than that of Ang Ⅱ group(P＜0.05).Tunel staining showed that the number of apoptosis in the Ang Ⅱ group was higher than that in the control group(P＜0.05);the number of apoptosis in the dapagliflozin group 1 and the Dapagliflozin group 2 was lower than that in the Ang Ⅱ group(P＜0.05).The cas-pase3 activity of the cells in the Ang Ⅱ group was higher than that of the control group(P＜0.05)but lower in dapagliflozin group 1 and the dapagliflozin group 2(P＜0.05).The results of Western blotting showed that the ac-tivation of insulin-like growth factor 1 receptor(IGF1R)and Akt in the Ang Ⅱ group was lower than that in the control group(P＜0.05)but increased in the dapagliflozin group 1 and 2 cells(P＜0.05).Conclusion Dapa-gliflozin could directly act on cardiomyocytes to protect them from Ang Ⅱ-induced damage.

Objective:To analyze the diagnostic value of positron emission tomography/computed tomography (PET/CT) for mediastinal lymph node metastasis in non-small cell lung cancer (NSCLC) patients.Methods:A retrospective analysis was conducted on the clinical data of 120 NSCLC patients admitted to the Suqian Hospital Affiliated to Xuzhou Medical University from July 2017 to June 2021. All patients underwent preoperative chest CT and PET/CT examination ( 18F-FDG imaging agent), and underwent total thoracoscopic lobectomy+ mediastinal lymph node dissection. Using the pathological results obtained from surgery as the gold standard, the diagnostic efficacy of chest CT and PET/CT examination for mediastinal lymph node metastasis in NSCLC patients was analyzed. Results:The surgical pathological results showed that 53 out of 120 patients had lymph node metastasis (33 cases of adenocarcinoma, 17 cases of squamous cell carcinoma, and 3 cases of adenocarcinoma), with 15, 32, and 6 cases of pN1, pN2, and pN3 staging, respectively; Preoperative chest CT examination identified 28 cases of true positive, 52 cases of true negative, 15 cases of false positive, and 25 cases of false negative with mediastinal lymph node metastasis, while PET/CT examination identified 44 cases, 61 cases, 6 cases, and 9 cases, respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT in diagnosing mediastinal lymph node metastasis were higher than those of chest CT (all P<0.05); The consistency rate between PET/CT examination of lymph node metastasis N stage and surgical N stage [79.25% (42/53)] was higher than that of chest CT examination [45.28% (24/53)] ( P<0.05); The maximum standard uptake value (SUV) of lung cancer primary lesion in patients with mediastinal lymph node metastasis was higher than that in patients without lymph node metastasis ( P<0.05). Conclusions:PET/CT examination has high diagnostic value for mediastinal lymph node metastasis in NSCLC patients, and those who have objections to the results need further thoracoscopic examination to clarify the diagnosis.

Tumor immunotherapy is a therapeutic modality that uses immunological principles and methods to activate and enhance the body''s immune system to generate immune response for the removal of tumour cells. Many new immunotherapeutic agents have demonstrated effective anti-tumour capabilities, yet their clinical use is challenging due to the complex mechanisms of tumour immune escape. Meanwhile, these drugs would accumulate in different tissues and organs in the human body and be unable to achieve precise and specific targeting therapeutic effects, resulting in serious immune-related adverse effects, which greatly hinders the clinical potential of immunotherapy.Nanodrug delivery systems can deliver immunotherapeutic drugs to target tissues or specific immune cells precisely, thereby enhancing immune effects and reducing side effects.This paper reviews the research progress of nanodrug delivery systems in tumour immunotherapy in recent years based on the regulatory mechanism of the anti-tumour immune response, with a prospect of the challenges and development in this field.

Partial thickness rotator cuff tears(PTRCTs) are a common cause of shoulder pain and dysfunction in adults, which are seen in middle-aged and older adults and young adults in over-the-shoulder sports(throwing sports are the most common). PTRCTs include partial tears on the articular side, partial tears on the bursal side, and intratendinous tears. Tears on the articular side are 2-3 times more likely than on the bursal side, but intratendinous tears are the most common type. The treatment of PTRCTs consists of both conservative and surgical treatments. Conservative treatment is suitable for most patients with PTRCTs, and recommended as the primary treatment for PTRCTs because of its good clinical efficacy and patients′ willingness to accept it. However, there is no genaral consensus on the best treatment and the results reported in the literature are controversial. In this paper, the anatomy, epidemiology, pathogenic factor, diagnosis and treatment progress of PTRCTs are summarized in light of relevant domestic and international studies in recent years to provide reference for clinical diagnosis and treatment.

Objective To study the cognitive impairment in SD rats after intermittent hypoxia (IH),and explore the relation of miR-26b up-regulated expression and neuron apoptosis in the hippocampus of SD rats after IH.Methods Eight-week-old male SD rats (n=20,each weighing approximately 300±10 g) were randomly divided into normal oxygen control group,IH 1-week group,IH 2-weeks group and IH 4-weeks group (n=5).Rats in the later three groups were given IH for different times,and rats in the normal oxygen control group were given normal oxygen.The spatial learning and memory abilities were detected by Morris Water Maze (MWM) in the normal oxygen control group and IH 4-weeks group.The levels of apoptosis proteins Caspase3 and Bax and anti-apoptosis protein Bcl-2 in the hippocampus of 4 groups were detected by Western blotting.The miR-26b expression level in the 4 groups was detected by real time-PCR.Results (1) The results of MWM revealed that the mean escape latency in the IH 4-weeks group was significantly prolonged as compared with that in the normal oxygen control group (P＜0.05);the time entering into the target quadrant in the IH 4-weeks group ([22.0±6.7] s) was significantly shorter than that in the normal oxygen control group ([39.8±8.8] s,P＜0.05).(2) Western blotting indicated that up-regulated expressions of apoptosis proteins Bax and Casepase3 and down-regulated expression of anti-apoptosis protein Bcl-2 in the IH 1-week group,IH 2-weeks group and IH 4-weeks group were noted as compared with those in the control group,with significant differences (P＜0.05);significantly higher apoptosis protein Bax and Casepase3 expressions in the IH 1-week group were noted as compared with those in the IH 2-weeks group and IH 4-weeks group (P＜0.05),while significantly decreased Bcl-2 expression in the IH 1-week group was noted as compared with that in the IH 2-weeks group and IH 4-weeks group (P＜0.05).(3) The results of real time-PCR revealed that the miR-26b expression level in the hippocampus was up-regulated in the IH 1-week group,IH 2-weeks group and IH 4-weeks group as compared with that in the control group,with significant differences (P＜0.05);miR-26b expression level in the IH 1-week group was significantly higher as compared with that in the IH 2-weeks group and IH 4-weeks group (P＜0.05).Conclusion The miR-26b up-regulated expression in the hippocampus might refer to Bax /Bcl-2-related mitochondrial apoptotic signaling pathway after IH brain injury;miR-26b could be a potential mean ofgene therapy after IH brain injury.

Background::Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy. Methods::Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification. Results::A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1. Conclusions::The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.

Objectives:To report a novel mutation site in the pathogenic gene TTR of transthyretin cardiac amyloidosis(ATTR-CA),and to identify family members at risk,and provide suitable clinical diagnosis and treatment. Methods:A retrospective analysis was conducted on the clinical data of the proband with ATTR-CA who visited the Department of Cardiology,the First Affiliated Hospital of Zhengzhou University in March 2021.The proband underwent whole exome sequencing using high-throughput methods to detect mutation genes.Sanger sequencing was used to test candidate pathogenic loci in suspected family members,and relevant literature was reviewed. Results:Among 51 individuals spanning 5 generations in the pedigree,10 family members(including the proband)carried the heterozygous TTR gene c.163A>G mutation,resulting in the amino acid residue at position 55 changing from lysine(Lys)to glutamic acid(Glu).This mutation follows an autosomal dominant inheritance pattern,with early onset in adulthood,rapid progression,and presenting as a mixed-type ATTR-CA.Five mutation carriers had different clinical manifestations,while the remaining 5 mutation carriers,who are at younger age,have not yet shown symptoms.Within the pedigree,7 individuals died(the proband's uncle[Ⅱ-1]who died from stroke at 65 years old,the rest 6 family members died from heart disease before the age of 50). Conclusions:According to the American College of Medical Genetics and Genomics guidelines,TTR gene Lys55Glu mutation is classified as likely pathogenic,this mutation site has not been reported in the literature before.Present study adds clinical evidence that might broaden the spectrum of TTR mutations.

Objective To investigate the changes of microglia cell phenotypes in the injured brains of rats following repetitive mild traumatic brain injury (rmTBI).Methods Sixty male SD rats were randomly divided into sham-operated group,injury of one-week group,injury of two-week group,injury of four-week group,and injury of six-week group (n=12).Rats in the injury groups were induced rmTBI models by controlled cortical impact (CCI),and rats in the sham-operated group were only performed bone window opening without hitting.Six rats from each group were sacrificed;immunofluorescent staining was used to detect the Iba-1 positive microglial cells in the injured cortex and changes ofmicroglia subsets in the injured brain after rmTBI were analyzed by flow cytometry.Results As compared with the sham-operated group,the injury of one-week group and injury of six-week group had significantly increased percentages of Iba-1 positive microglial cells in the injured cortex (19％ and 12％,P＜0.05).flow cytometry indicated that CD451ow/CD11b+ cells were the microglial cells,accountting for 90％ ofCD11b+ cells;as compared with the sham-operated group,the injury of one-week group,injury of two-week group,injury of four-week group,and injury of six-week group had significantly increased M1 type microglial cells (P＜0.06),with injury of six-week group enjoying the highest level;as compared with the sham-operated group,the injury of one-week group,injury of two-week group and injury of four-week group had significantly increased M2 type microglial cells (P＜0.06),with injury of two-week group enjoying the highest level.Conclusion Dynamic changes ofmicroglia subsets after rmTBI are noted,which reveals that different subsets of microglia phenotypes might play their unique roles in the acute or chronic phases after rmTBI.