Hepatocellular carcinoma(HCC)is one of the most common malignant tumors.Tyrosine kinase inhibitors have been used in the mainstream treatment of HCC for many years,but their therapeutic efficacy is limited and the prognosis of patients is very poor.In recent years,the rapid rise of immunotherapy has provided a new direction for tumor treatment.In particular,immune checkpoint inhibitors have shown excellent clinical effect in the treatment of various solid tumors,including HCC.This article reviews various immune checkpoint inhibitors related to HCC and their clinical practice and research progress,aiming to provide a relevant reference and theoretical basis for the immunotherapy of HCC.

Tumor immunotherapy,recognized as the fourth major treatment modality alongside surgery,radiotherapy,and chemotherapy,fundamentally relies on mobilizing and enhancing the body's intrinsic immune system to achieve the precise targeting and elimination of neoplastic lesions.In this therapeutic framework,macrophages derived from blood monocyte differentiation serve as critical components of the innate immune defense system and exert profound impacts within the tumor microenvironment(TME).As the dominant inflammatory cell population infiltrating the TME,tumor-associated macrophages(TAMs)not only perform a key function in immune regulation but also serve as a paradigm for the connection between inflammation and tumors.Therapeutic strategies targeting TAMs aim to reverse the immunosuppressive milieu of the TME through multifaceted regulatory mechanisms,including cellular depletion or functional reprogramming,thereby effectively impeding tumor progression.This review systematically analyzes the intricate immune regulatory mechanisms of macrophages in tumor immunotherapy and synthesizes research advancements in major therapeutic agents targeting TAMs,aiming to provide researchers in the field of tumor immunotherapy and developers of macrophage-modulating pharmaceuticals with novel theoretical insights and practical guidelines.

Hepatocellular carcinoma(HCC)is one of the most common malignant tumors.Tyrosine kinase inhibitors have been used in the mainstream treatment of HCC for many years,but their therapeutic efficacy is limited and the prognosis of patients is very poor.In recent years,the rapid rise of immunotherapy has provided a new direction for tumor treatment.In particular,immune checkpoint inhibitors have shown excellent clinical effect in the treatment of various solid tumors,including HCC.This article reviews various immune checkpoint inhibitors related to HCC and their clinical practice and research progress,aiming to provide a relevant reference and theoretical basis for the immunotherapy of HCC.

Tumor immunotherapy,recognized as the fourth major treatment modality alongside surgery,radiotherapy,and chemotherapy,fundamentally relies on mobilizing and enhancing the body's intrinsic immune system to achieve the precise targeting and elimination of neoplastic lesions.In this therapeutic framework,macrophages derived from blood monocyte differentiation serve as critical components of the innate immune defense system and exert profound impacts within the tumor microenvironment(TME).As the dominant inflammatory cell population infiltrating the TME,tumor-associated macrophages(TAMs)not only perform a key function in immune regulation but also serve as a paradigm for the connection between inflammation and tumors.Therapeutic strategies targeting TAMs aim to reverse the immunosuppressive milieu of the TME through multifaceted regulatory mechanisms,including cellular depletion or functional reprogramming,thereby effectively impeding tumor progression.This review systematically analyzes the intricate immune regulatory mechanisms of macrophages in tumor immunotherapy and synthesizes research advancements in major therapeutic agents targeting TAMs,aiming to provide researchers in the field of tumor immunotherapy and developers of macrophage-modulating pharmaceuticals with novel theoretical insights and practical guidelines.

Objective:To study the curative effect of platelet-rich plasma (PRP) combined with internal fixation with hollow screws on femoral neck fractures.Methods:The clinical data of 160 patients with femoral neck fracture were retrospectively analyzed who had been treated by internal fixation with hollow screws at Orthopedic Department Ⅲ, The Second Affiliated Hospital to Luohe Medical College from May 2012 to May 2018. According to whether PRP was used or not to assist their internal fixation, they were divided into a PRP group ( n=80) and a control group ( n=80). In the PRP group, there were 46 males and 34 females with an age of 52.3 years±7.6 years, and one case of type Ⅰ, 5 cases of type Ⅱ, 57 cases of type Ⅲ and 17 cases of type Ⅳ by the Garden classification. In the control group, there were 41 males and 39 females with an age of 50.6 years ± 7.3 years, and 2 cases of type Ⅰ, 7 cases of type Ⅱ, 51 cases of type Ⅲ and 20 cases of type Ⅳ by the Garden classification. The 2 groups were compared in terms of fracture healing time, nonunion, femoral head necrosis and Harris hip scores. Results:The 2 groups were comparable because their preoperative general data showed no significant differences ( P>0.05). The 160 patients obtained follow-up for 12 to 36 months. The PRP group showed significantly shorter fracture healing time (4.3 months ± 1.0 months), significantly lower incidences of nonunion [0% (0/80)] and avascular necrosis of femoral head [3.8% (3/80)] than the control group [7.3 months ± 1.3 months, 7.5% (6/80) and 15.0% (12/80), respectively] (all P< 0.05). The Harris scores at 6 and 12 months after operation for the PRP group (88.7±5.3 and 94.2±4.8) were significantly higher than those for the control group (81.4±4.6 and 84.2±5.2) (both P<0.05). Conclusion:In the treatment of femoral neck fractures, compared with internal fixation with hollow screws alone, platelet rich plasma combined with internal fixation with hollow screws can significantly shorten fracture healing time, reduce incidence of avascular necrosis of the femoral head and improve functional recovery of the hip joint.

Objective To discuss the effects and the possible mechanismof curcumin on pulmonary functions and expression of TGF-β1 and NF-κB in paraquat-induced pulmonary fibrosis of rats.Methods SPF Wistar rats were randomly (random number) divided into three groups:paraquat-poisoned group (PQ group,with PQ 50 mg/kg by gavage),Curcumin-treatment group (PC group after 30,with curcumin (200 mg/kg) by intraperitoneal injection),and Blank group (B group,with same volume of sterile saline at the same time).After 14 d,the lung function of rats was observed,and the expression of TGF-β1 and NF-κB protein were detected by immunohistochemistry.Results The survival rates of mice significant difference in the PC and PQ groups with (70.83％ vs.41.67％,P ＜0.05).Compared with the B group,lung function index (Te,PIF,PEF,EF50,TV,F) of PQ group significantly decreased (P ＜ 0.05,P ＜ 0.01).Compared with the PQ group,lung function index (Te,PEF,TV,F) of PC group significantly increased (P ＜ 0.05 or P ＜ 0.01).There are some expression of lung tissues of rats with TGF-β1,NF-κB in B group.Compared with B group,PQ group significantly enhanced (P ＜0.01or P ＜0.05).Compared with the PQ,PC group significantly decreased (P ＜ 0.01 or P ＜ 0.05).Conclusions Curcumin can relieve paraquat-induced pulmonary fibrosis by inhibiting the over expression of TGF-β1,NF-κB in lung tissue of rats.

Objective To observe the effects of curcumin on pulmonary fibrosis and functions on paraquat (PQ)-challenged rats, and investigate the possible mechanism. Methods 108 SPF Wistar rats were divided into three groups according to random number sheet: normal saline (NS) control group, PQ model group and curcumin-treatment group. The rats in each group were subdivided into three subgroups according to different time points (3, 7, 14 days), with 12 rats in each subgroup. PQ-challenged models were reproduced by intragastrical administration of PQ solution 50 mg/kg, and those in NS control group were given the equal volume of NS. After 30 minutes, the rats in curcumin-treatment group were given 200 mg/kg of curcumin by intraperitoneal injection, and those in NS control group and PQ model group were given the equal volume of NS. At 3, 7, 14 days, the tidal volume (VT) was examined, and the blood was drawn from femoral artery for blood gas analysis. Then the rats were sacrificed and the lung tissues were harvested, the hydroxyproline (Hyp) content was measured by alkaline hydrolysis; the expression of transforming growth factor-β1 (TGF-β1) was determined by immuno-histochemistry; the distribution and the change of the pulmonary collagen fiber were observed after Masson staining. Results After exposure to PQ, the VT and arterial partial pressure of oxygen (PaO2) were decreased gradually, and the levels of Hyp and TGF-β1 were increased gradually, reaching the trough or the peak at 14 days, which were significantly lower or higher than those in NS control group [14-day VT (mL):1.52±0.33 vs. 2.81±0.47, 14-day PaO2(kPa): 5.87±0.95 vs. 14.15±1.02, 14-day Hyp (μg/mg): 3.12±0.06 vs. 1.14±0.05, 14-day TGF-β1 (integral A value): 29.72±4.27 vs. 4.15±0.52, all P < 0.01]. After intervene of curcumin, the parameters were significantly improved as compared with those of PQ model group [14-day VT (mL): 2.34±0.19 vs. 1.52±0.33, 14-day PaO2(kPa): 10.23±1.01 vs. 5.87±0.95, 14-day Hyp (μg/mg): 2.31±0.04 vs. 3.12±0.06, 14-day TGF-β1 (integral A value): 15.46±2.89 vs. 29.72±4.27, all P < 0.01]. It was shown by Masson staining that in PQ model group, with the PQ-poisoned time prolonging, diffused pulmonary fibrosis and a large number of collagen deposition were observed gradually, and the most serious collagen deposition was observed at 14 days; after intervene of curcumin, pulmonary fibrosis was alleviated significantly at different time points as compared with the PQ model group. Conclusion Curcumin can enhance the pulmonary function by reducing the deposition of collagen fiber and inhabiting pulmonary fibrosis of PQ-poisoned rats.

Objective To observe the effects of curcumin on the lung collagen area and the expression of TNF-α,IL-6 and NE in paraquat-poisoning rats at different intervals,and discuss the possible mechanism of curcumin antagonizing paraquat poisoning.Methods A total of 108 SPF Wistar rats were divided into three groups (random number):blank group (B group) for control,paraquat poisonin group (PQ group) and curcumin-treatment group (PC group).The rats of PQ group and PC group were given paraquat (50 mg/kg) by gavage,and the rats of B group were given equal volume of sterile saline solution at the same time.Thirty minutes later,the rats of PC group were given curcumin (200 mg/kg) by intraperitoneal injection,and rats of B group and PC group were given equal volume of sterile saline solution instead.At 3 d,7 d and 14 d after modeling,the distribution and pathological changes of lung tissue and collagen fiber were observed by HE and Masson staining.The concentration of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-immunoassay.The lung neutrophil elastase (NE)expression was observed by immuno-histochemical method.Result Compared with B group,PQ group had pulmonary alveolitis in different degrees at different intervals,and the most serious pulmonary alveolitis was observed at 7 d after modeling.Diffused pulmonary fibrosis of the lung tissue and a large area of collagen fiber deposition were observed especially at 14 d after modeling,as well as the expression of NE was observed obviously,especially at 14 d after modeling.The concentration of TNF-α,IL-6 in serum were significantly increased (P ＜ 0.05,P ＜ 0.01).Compared with PQ group,the pulmonary alveolitis and fibrosis obviously in PC group with obvious reduction in the expression of NE and significant descrease in the concentrations of TNF-o and IL-6 (P ＜ 0.05).Conclusion Inhabiting inflammatory factors to alleviate the seriousness of alveolar inflammation and pulmonary fibrosis might be one of the mechanism of treatment with curcumin for paraquat poisoning rats.

Objective To investigate the treatment effect of aescuven forte on the postoperative complications of breast cancer.Methods One hundred and twenty patients with breast cancer radical surgery were randomly divided into control group(n =60) and treatment group(n =60).Patients in control group were given postoperative routine treatment,while in treatment group were administrated aescuven forte pills at 300 mg orally,2 times/day for 4 weeks beside the conventional treatment.Results (1)After the 1st,2nd weeks therapy,the flap congestion disappear rate in the treatment group were 80.0％ (48/60) and 93.3％ (56/60),better than that in the control group 60.0％ (36/60) and 71.6％ (43/60),the difference was statistically significant (P ＜ 0.05).However this trend was not seen in third weeks treatment (P ＞ 0.05).(2) The total efficiency of remission of upper limb edema was 93％ (56/60),higher than that in control group 77％ (46/60),the difference was statistically significant(x2 =5.17,P ＜ 0.05).(3) Visual analogue scale(VAS) pain score in treatment group were decreased form (8.87 ±0.74) in before treatment to (3.21 ±0.92) at after treatment.And the VAS score in control was from (8.91 ±0.85) down to (4.87 ± 1.34),the difference was statistically significant (P ＜ 0.05).Moreover VAS score in treatment group was lower than that in control group (P ＜ 0.05).(4) There was no adverse effect of the medication process.Conclusion Aescuven forte showed a ability to reduce congestion disappear time of breast cancer and shorten the recovery time of upper limb swelling and pain and other symptoms.

Objective To evaluate the clinical characteristics and in-hospital mortality of acute myocardial infarction patients (AMI) with diabetes mellitus (DM) and to analyze the risk factors of in-hospital mortality of AMI. Method A total of 1023 patients with diagnosis of AMI complicated with or without DM admitted between 2000 and 2004 were analyzed to find out the clinical characteristics, in-hospital complications and mortality. Of them, 164 (16.03%) were complicated with DM. The data were analyzed by using Mann-Whitney U or chi-square test. The multivariate logistic regression analysis was used to find out the risk factors of in-hospital mortality of patient with AMI. Results In comparison with non-DM patients, the females were predominant in number over males in the DM patient cohort (42.2% vs. 28.9%, P < 0.05), the incidence of hypertension (71.7% vs. 41.6%, P < 0.01) and rate of angina (57.3% vs. 48.3%, P < 0.06). The admission time of DM patients was delayed rather than that of non-DM patients. Coronary angiography revealed that the rate of three-vessel in-volved was higher in DM patients than in non-DM patients (48.4% vs. 25.4%, P < 0.05. During hospital stay, AMI patients with DM presented mar frequently with arrhythmias, pulmonary edema (18.9% vs. 10.5%, P <0.01) and increase in in-hospital mortality (17.7% vs. 9.2%, P < 0.01) compared with non-DM patients. Di-uretics (43.9% vs. 32%, P <0.01) and digitalis (27.4% vs. 16.8%, P <0.01) were more frequently used in DM patients rather than in non-DM patients. Compared to medication, primary coronary intervention (PCI) with placement of intra-vascular stent significantly decreased the mortality of DM patients (χ~2 = 4.536, P < 0.05).Logistic regression analysis showed DM was an independent risk factor for in-hospital mortality (OR = 2.109;95% CI:1.229-3.619). Conclusions AMI patients with DM exhibit more risk factors for in-hospital complications and higher mortality than those without DM.DM is an independent risk factor for in-hospital mortality of patients with AMI.