In recent years, benefiting from the increasing understanding of tumor immunity, the application of immunotherapy especially immune checkpoint inhibitors in the clinic has achieved great success. Although immunotherapy shows great potential for antitumor therapy, many challenges are currently facing. The limited benefit population is one of the important issues, and the development of new therapeutic strategies to increase the proportion of the population benefiting immunotherapy is of great clinical importance. As one of the traditional means of antitumor therapy, increasing evidence shows that it plays an important role in antitumor immune mechanisms. Chemotherapy can improve the sensitivity of tumor cells to programmed death-1(PD-1)/PD-L1 inhibitors by affecting the immune microenvironment and activating antitumor immune responses. Moreover, chemotherapy can affect the tumor cells themselves, upregulate the expression of PD-L1, and induce PD-L1-mediated tumor immunosuppressive phenotype, thereby increasing the therapeutic targets of PD-1/PD-L1 inhibitors. A large body of evidence from clinical studies has also suggested a synergistic effect between combination chemotherapy and immune checkpoint inhibitors in multiple malignancies, and combination therapy is expected to be a novel immunotherapeutic strategy. This paper systematically reviews the evidence from relevant basic and clinical studies, analyzes and summarizes the interaction relationship between chemotherapy and immunotherapy, aiming to provide new ideas for enhancing antitumor immune responses, and at the same time provides a corresponding theoretical basis for clinical combination chemotherapy and immunotherapy.

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are the important endocrine hormones for human, and their associated diseases (e. g. acromegaly and growth hormone deficiency) can lead to obviously increased morbidity and mortality secondary to cardiovascular, cerebrovascular and respiratory diseases. Clinically, the determination and closely monitoring of serum GH and IGF-1 are important means for diagnosing, assessing curative effect and formulating post-treatment follow-up plans of such diseases, and have received extensive concern from clinicians. Although the levels of serum GH and IGF-1 are consistent in most cases, more and more studies have reported that the results of serum GH and IGF-1 are unreasonable or even contradictory. Therefore, in the conditions of inconsistent serum GH and IGF-1 levels, reliable biochemical criteria for assessing disease status and control degree are currently controversial, and their rational interpretation remains a clinical challenge. In present paper, the influence of serum GH and IGF-1 detection methods, physiological and pathological states, and drugs on the detection results and the possible reasons or mechanisms are explained in detail, and proposes that it is necessary to carefully sort out the factors that may lead to unreasonable results in clinic, in order to judge the detection results more accurately and conduct appropriate diagnosis and treatment of the related diseases.

Surgery and resuscitation are the core capabilities of combat casualty care. Early treatment should be carried out within 3 hours, and divided into two phases, emergency treatment and surgical resuscitation, emphasizing the capability building of resuscitation and surgery. This paper interprets the capability requirements of the early casualty care level. According to the domestic and international progress in the care of civilian trauma and combat casualty, the relationship between "surgery" and "resuscitation" in the early treatment level of combat casualty, and the key technological progress are summarized, indicating that only the coordinated development of surgery and resuscitation ability and mutual support can provide safe, standardized and efficient treatment and reduce the death rate of the combat casualties.

Objective To observe the effects and possible mechanism of exposure to high altitude environment on liver function in rats. Methods Forty-eight healthy male SD rats were randomly divided into plain group, plateau 1-month group, plateau 2-month group and plateau 4-month group (12 each). Rats in plain group were fed at an altitude of about 500 m for 1 month, and in the plateau groups were fed in a simulated chamber of high altitude (5000 m) for 1 month, 2 months and 4 months, respectively. Serum and liver tissue were collected at the end of the model. The contents of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were measured with automatic biochemical analyzer. The pathological morphology of liver tissue was observed by HE staining. The levels of reduced glutathione (GSH) and superoxide dismutase(SOD) in liver tissue were measured by ELISA. The ultra structural changes of hepatocytes were observed by transmission electron microscope. The relative expressions of autophagy associated proteins LC3-Ⅱ and Beclin-1 were determined by Western blotting. Results Compared with the plain group, the serum levels of ALT, AST and TBIL significantly increased in the plateau 2-month group (P<0.05); compared with the plateau 2-month group, the serum levels of ALT, AST and TBIL significantly decreased in the plateau 4-month group (P<0.05). HE staining showed that the lobule structure of liver tissue in each group was clear without obvious inflammatory infiltration, cell edema or necrosis. The results of transmission electron microscope showed that the number of autophagy corpuscles in hepatocytes of rats was significantly higher in plateau 1-month group and plateau 2-month group than in plain group, and was significantly lower in plateau 4-month group than in plateau 2-month group. Western blotting and ELISA results showed that the relative expression levels of LC3-Ⅱ and Beclin-1 protein increased significantly, while the GSH and SOD levels decreased significantly in plateau 1-month group and plateau 2-month group than in the plain group (P<0.05); the relative expression levels of LC3-Ⅱ and Beclin-1 protein significantly decreased, and the levels of GSH and SOD significantly increased in plateau 4-month group than in plateau 2-month group (P<0.05), but no significant differences compared with those in plain group(P>0.05). Conclusion In the process of adapting to hypobaric and hypoxic environment, abnormal changes of liver function indexes of rats occurred, the mechanism may be related to the changes of oxidative stress level and autophagy of hepatocytes.

Objective To explore the effect of hsa-microRNA-203-3p (miR-203) targeted-regulating Cullin2 (CUL2) on the biological characteristics of human papillomavirus 16 (HPV16) positive cervical cancer cells. Methods A total of 10 patients underwent cervical cancer screening from September 2018 to September 2019 in the Department of Obstetrics and Gynecology, the Second Hospital of Shanxi Medical University. HPV genotyping was performed as single HPV16 positive, and pathological examination showed cervical squamous cell carcinoma (SCC). Ten corresponding paracancer normal tissue samples were collected as control group. Real-time quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expression of miR-203 in cervical squamous cell carcinoma and corresponding adjacent tissues, cervical cancer cell line (SiHa) and human immortal keratinocyte line (HaCaT) cells. GO and KEGG enrichment were applied to analyze the functions and pathways miR-203 involved. The regulatory relationship between miR-203 and CUL2 were verified via TargetScan website and dual luciferase reporter assay. The miR-203 mimics or inhibitor were transfected into SiHa cells to establish cell models of high and low expression of miR-203,and the expressions of CUL2 mRNA and protein were detected by qRT-PCR and Western blotting. The proliferation, migration and apoptosis of SiHa cells were assessed by CCK-8, scratch assay and Annexin V-APC/PI double staining, respectively. Results Results of qRT-PCR indicated that, compared with the corresponding adjacent tissues and HaCaT cells, the relative expression level of miR-203 decreased obviously in both cervical SCC tissues and SiHa cells (P<0.01). The results of GO and KEGG enrichment methods showed that miR-203 was widely involved in the ubiquitination process and the signaling pathways involved in the malignancies. TargetScan website and dual-luciferase reporter assay showed that the targeting regulatory relationship existed between miR-203 and CUL2 (P<0.01). qRT-PCR and Western blotting indicated that overexpression of miR-203 reduced the expressions of CUL2 mRNA and protein (P<0.05 or P<0.01); While low expression of miR-203 up-regulated the expressions of CUL2 mRNA and protein (P<0.01). CCK-8, scratch experiments and Annexin V-APC/PI double staining method confirmed that overexpression of miR-203 decreased proliferation rate and migration rate of SiHa cells (P<0.01), and elevated cell apoptosis rate (P<0.05). In contrast, low expression of miR-203 increased the proliferation rate and migration rate of SiHa cells (P<0.01), and reduced the apoptosis rate(P<0.01). Conclusion The miR-203 might suppress the biological characteristics of HPV16-positive cervical cancer cells SiHa by targeting CUL2, and it was expected to become a new candidate gene in diagnosis and treatment of cervical cancer.

Objective Use aspirin to induce mouse inflammatory bowel disease model, and investigate whether Lactobacillus acidophilus LA-GHB1756 can alleviate this type of enteritis injury. Methods A total of 40 male BALB/c mice (6-8 weeks old) was randomized into four groups: control group, aspirin group, LA low-dose group, and LA high-dose group. Except for the control group, the remaining groups were given 0.5 mg/(100 g·d) aspirin solution by gavage for eight weeks to induce inflammatory bowel disease. The LA low-dose and high-dose groups received an additional 2000 cfu/(100 g·d) and 10 000 cfu/(100 g·d) of LA-GHB1756 bacterial liquid, respectively. Accordingly, the control and aspirin groups received the same volume of normal saline through gavage. We then monitored the mouse's body weight, defecation status, hair color, and other conventional indicators, colon macroscopic and pathological staining. We used ELISA to detect intestinal tissue MPO content, serum tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) expression. We employed Western blotting to detect intestinal tissue NF-κB p65 expression levels. Results The general observation of mice in each group showed that LA-GHB1756 could improve the diarrhea, hair, and mental status of aspirin-induced mice. In the 8th week, the body weight of mice in the aspirin group was (21.6±0.5) g. The body weight was statistically significantly improved in the LA low-dose and high-dose groups, which were (22.8±0.4) g and (23.1±0.3) g, respectively (P<0.05). The colon morphology and pathological results showed that LA-GHB1756 could alleviate intestinal mucosal edema and inflammation caused by aspirin in mice. The colon length of mice in the aspirin group was(5.80±0.43) cm, and the colon length of low-dose and high-dose LA groups was (6.17±0.15) cm and (6.50±0.26) cm, respectively. This length improvement was statistically significant (P<0.05). The results of MPO content in intestinal tissues showed that aspirin group was (95.90±11.34) pg/mg, the MPO content in LA low-dose group and LA high-dose group were (76.03±8.72) pg/mg and (51.40±9.12) pg/mg respectively, which was significantly decreased compared with aspirin group, the difference was statistically significant (P<0.05). The results of serum TNF-α and IL-6 expression showed that the concentrations of TNF-α and IL-6 in aspirin group were (238.75±17.80) pg/mg and (292.00±15.51) pg/mg, respectively, while those in LA low-dose group were (207.75±12.04) pg/mg and (250.25±11.50) pg/mg, respectively, LA high-dose group were (80.25±10.24) pg/mg and (108.50±13.38) pg/mg, respectively. Compared with aspirin group, TNF-α and IL-6 contents in LA low-dose group and LA high-dose group were statistically significantly decreased (P<0.05). The expression of NF-κB p65 was increased up to 5.07 fold in aspirin group when compared with control group. This level was statistically significantly decreased to 83.74% and 82.95% in LA low-dose and high-dose groups, respectively (P<0.05). Conclusion LA-GHB1756 can relieve intestinal inflammation in mice caused by aspirin, this effect may be related to the inhibition of MPO and NF-κB p65 expression in intestinal tissue.

Objective To investigate the effect and mechanism of homocysteine on apoptosis and proliferation of cardiomyocytes. Methods Cardiomyocytes were stimulated with homocysteine at the concentration of 3 mmol/L for 24 h. Cells were divided into control group and homocysteine group (Hcy group). Western blotting was detected the expression of TLR4,Myeloid differentiation factor 88 (MyD88), NF-κB, p-NF-κB, the expression of apoptosis related proteins Bax, cleaved-caspase-3 and anti-apoptotic protein Bcl-2; Flow cytometry was detected the apoptosis rate of cardiomyocyte, EdU staining was observed the proliferation of cardiomyocytes. After TLR4 interference fragment was transfected into cardiomyocytes, the interference fragment was verified by Western blotting. The cells were transfected with si-NC or si-TLR4 and treated with Hcy. Western blotting was detected the expression of MyD88, NF-κB and p-NF-κB, the expression of apoptosis related protein and anti-apoptosis protein in cardiomyocytes; The apoptosis rate of cardiomyocytes was detected by flow cytometry; The apoptosis of cardiomyocytes was observed by EdU staining. Results Compare with control group, Western blotting showed that TLR4, MyD88 and p-NF-κB significantly increased in Hcy group (P<0.01); The expression of apoptosis related proteins Bax and cleaved-caspase-3 increased and the expression of anti-apoptotic protein Bcl-2 was decreased (P<0.01); Compared with si NC+Hcy group, the expression of TLR4, MyD88 and p-NF-κB decreased (P<0.01), the expression of apoptosis related protein decreased (P<0.01), and the expression of anti-apoptosis protein increased in si-TLR4+Hcy group (P<0.01); Compare with control group, the results of flow cytometry showed that the apoptosis rate of cardiomyocytes increased in Hcy group (P<0.01); Compared with si-NC+Hcy group, the apoptosis rate of si-TLR4+Hcy group decreased (P<0.01). Compared with control group, EdU staining showed that the number of positive cells decreased in Hcy group (P<0.01); Compared with si-NC+Hcy group, the number of positive cells increased in si-TLR4+Hcy group (P<0.01). Conclusion Hcy can induce apoptosis and inhibit proliferation of cardiomyocytes, the mechanism may have something to do with TLR4/NF-κB signaling pathway.

Objective The novel μ opiate receptor (MOR) antagonists with biological activity was searched based on computer aided drug design method. Methods The MOR was employed as the target protein, and the Glide module of Schrodinger software was used to virtually screen the numerous compounds included in ZTNC-15 open source compound database. According to the molecular docking score, skeleton structure, binding mode and compound acquisition, one compound that may be as an antagonist was selected. The anti-fentanyl-induced acute death model of mice and the experiment of improving fentanyl-induced respiratory depression of rats were used to evaluate the biological activity of A₆ against MOR. Finally, molecular dynamics simulation method was employed to analyze the possible mechanism of MOR-A₆ interaction. Results The molecular docking score of compound A₆ was comparable to that of naloxone. The results of animal experiments showed that the LD₅₀ value of fentanyl-induced death of mice in A6 prevention administration group [13.2(95%CI 12.0-14.5) mg/kg] was 1.3 times and higher than that in model group [10.5(95%CI 9.6-11.5) mg/kg], and the mortality of mice in experimental group was significantly lower than that in model group (P<0.05); Compared with model group, the carotid oxygen saturation (SaO₂) of rats in A₆ prevention administration group increased significantly at 15, 20 and 25 min after fentanyl injection (47.91%±3.17% vs. 62.63%±4.14%, 52.99%±3.92%vs. 69.57%±3.17%, and 58.16%±2.45% vs. 77.10%±4.93%, P<0.05). Molecular dynamics simulation of A₆ and MOR showed that ASP147 amino acid residue of A₆ is consistent with the predicted results of molecular docking, and has a large contribution on binding free energy. Conclusions A novel compound A₆ has obtained by virtual screening which could effectively antagonise fentanyl-induced acute toxic death in mice and improve fentanyl-induced respiratory depression in rats. The mechanism may be related to the hydrogen bond formation of ASP147 amino acid residue with MOR.

Objective To explore the cumulative metabolic indicators and the related risk factors for restenosis after intervention of lower extremity arteriosclerosis obliterans (LEASO). Methods Data were collected of 110 patients with arterial occlusive symptoms of low limbs who admitted to the Department of Hypertension and Endocrinology, Army Characteristic Medical Center, Army Medical University from January 2007 to July 2021 and met the criteria. All patients underwent low limbs interventional surgery and were followed up for more than 2 years. CT angiography (CTA) and ultrasound of both low limbs arteries were performed 2 years after surgery to clarify whether restenosis occurred and, based on the results of CTA and ultrasound, patients were divided into restenosis group (n=37) and non-restenosis group (n=73). The patients' basic information, pre- and post-operative hematological indices at 6 months, 1 year and 2 years were collected to compare and analyze the differences in basic clinical information, baseline values of metabolic indices (X_baseline) and cumulative exposure values (X_cum) between patients in the restenosis group and non-restenosis group, and binary logistic regression models were used to analyze the risk factors for post-interventional revascularization in patients with LEASO. Results The incidence was 33.6% of restenosis 2 years after intervention in patients with lower extremity arterial occlusive disease. The percentage of patients with smoking, the percentage of patients with Pan Atlantic Collaborative Group (TASC) typeⅡ (hereafter referred to as TASC type Ⅱ) C or D femoropopliteal artery lesions(hereafter referred to as TASC typeⅡ), hypersensitive C-reactive protein (hs-CRP), cumulative hypersensitive C-reactive protein(hs-CRP_Cum), cumulative low-density lipoprotein cholesterol (LDL-C_Cum), and cumulative triacylglycerol (TG_Cum) were significantly higher in restenosis group than those in non-restenosis group (P<0.05). The percentage of patients with regular postoperative use of antiplatelet agents and ankle-brachial index (ABI) were significantly lower than those in non-restenosis group (P<0.05). Binary logistic regression analysis showed that smoking (OR=4.158, P=0.040), TASC Ⅱ typing (OR=4.3, P=0.036), hs-CRP_Cum (OR=1.160,P=0.013), LDL-C_Cum (OR=2.313, P=0.003), and TG_Cum (OR=1.668, P=0.015) were the risk factors for restenosis 2 years after surgery, and regular postoperative use of antiplatelet drugs was a protective factor (OR=0.038, P=0.000). Conclusions Smoking,TASC Ⅱ typing, hs-CRP_Cum, LDL-C_Cum, and TG_Cum were the risk factors for restenosis of blood vessels after intervention in patients with lower extremity atherosclerotic occlusive disease. The regular use of postoperative antiplatelet drugs was a protective factor. Continuous smoking cessation, intensive lipid lowering, and anti-inflammation are the key factors to reduce the occurrence of postoperative restenosis, and early intervention of vascular lesions (TASC A-B) has better long-term effects.

Objective To analyze the clinical features, diagnosis and treatment and prognosis of acute megakaryocytic leukemia (AMKL), and then review the relative of AMKL. Methods Retrospectively study the clinical data of 14 AMKL patients admitted to Fujian Medical University Union Hospital and the First Affiliated Hospital of Gannan Medical University from January 2016 to May 2021, analyze and discuss the clinical features, diagnosis and differential diagnosis, treatment and prognosis of AMKL patients, and search domestic or foreign literature for the literature review at the same time. Results A total of 14 AMKL patients were included in present study, including 6 children [4 males and 2 females, with a median age of 2 years (13 months to 6 years)]; 8 adult patients [5 males and 3 females, with a median age of 57 (19-78) years]. The clinical manifestations of the patients were mainly non-specific symptoms of blood diseases. All patients underwent bone marrow biopsy, and a large number of primitive megakaryocytes were seen under the microscope. Except for 2 patients with incomplete flow immunophenotyping, cytogenetics and molecular biology tests, all the remaining 12 patients had megakaryocyte antigens (CD41, CD61, CD42b) expression, accompanied by genetic or molecular biology abnormalities. Except for 1 patient who survived after bone marrow transplantation and 1 patient who was lost to follow-up, the remaining 12 patients died, the median survival time was 5.5 (0–21) months. A total of 249 cases of AMKL patients in mainland of China (excluding Hong Kong, Macao and Taiwan) were reported from 2002 to 2022,of which 16 cases were transformed by other hematological tumor diseases: 6 cases were transformed by chronic myeloid leukemia(CML), 4 cases were transformed by myelodysplastic syndrome (MDS), 3 cases were transformed by myelofibrosis (MF), 2 cases were transformed by primary immune thrombocytopenia (ITP), and 1 was transformed by acute lymphoblastic leukemia (ALL).Among the 249 AMKL patients, 24 survived and 225 died. Most of the causes of death were disease progression, recurrence after chemotherapy or transplantation, severe infection, and fatal hemorrhage. Conclusions AMKL is rare and has an extremely poor prognosis with lack of specificity in clinical manifestations. It is helpful for diagnosis and differential diagnosis of AMKL by the results of bone marrow routine and pathology, flow cytometry, cytogenetics, molecular biology and electron microscopy. Clinical trials should be the first choice for the treatment of AMKL, correspondingly, close monitoring of measurable residual disease (MRD),and the remission induction chemotherapy combined with epigenetic drugs and targeted therapy may benefit patients. In addition,AMKL patients should undergo hematopoietic stem cell transplant as soon as possible after the first complete remission induced by standard chemotherapy, which will maximize the prognosis of patients.