BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.

Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

Objective To investigate the impacts of miR-141-3p on the proliferation,migration and epithelial-mesen-chymal transformation of glioma cells by regulating lysophosphatidic acid receptor 3(LPAR3).Methods RT-qPCR was used to detect the level of miR-141-3p and LPAR3 in glioma tissues and cells.Dual luciferase was used to de-tect the targeting relationship between miR-141-3p and LPAR3.The cells were divided into control group,miR-NC group,miR-141-3p mimics group,miR-141-3p mimics+pcDNA3.1 group,and miR-141-3p mimics+pcDNA-LPAR3 group,and then transfected with corresponding plasmids.RT-qPCR was used to detect the level of miR-141-3p and LPAR3 in cells.EdU method was used to detect cell proliferation.The scratch healing experiment was used to detect cell migration.Western blot was used to detect the expression of proteins related to cell proliferation,migration,and epithelial-mesenchymal transformation.Xenograft tumor model in nude mice was used to observe tumor formation.RT-qPCR was used to detect the level of miR-141-3p in tumor tissue.In addition,Western blot was performed to detect the expression of LPAR3,PCNA,and MMP-2.Results miR-141-3p was downregulated,whereas LPAR3 mRNA was upregulated in glioma tissues and U251,T98G,and CHG-5 cell lines(P＜0.05).There was a targeted binding site between miR-141-3p and LPAR3.miR-141-3p mimics significantly increased the ex-pression of miR-141-3p and E-cadherin,but decreased LPAR3 mRNA level,EdU-positive rate,scratch wound healing rate,and the expression of PCNA,cyclin D1,MMP-2,MMP-9,N-cadherin,and vimentin(P＜0.05).pcDNA-LPAR3 reversed effect on expression of these factors(P＜0.05).Tumor transplantation experiments in nude mice showed that miR-141-3p mimics reduced tumor volume,tumor weight,LPAR3,PCNA,and MMP-2 expres-sion,and increased the level of miR-141-3p(P＜0.05).Conclusions miR-141-3p can inhibit proliferation,mi-gration,and epithelial-mesenchymal transformation of glioma cells by down-regulating LPAR3.

Objective To investigate the protective effects of Ligilactobacillus salivarius Li01(L.salivarius Li01)against DNA damage induced by Helicobacter pylori(Hp),Benzo(a)pyrene(BaP),and Hp+BaP,and to evaluate the probiotic properties of L.salivarius Li01.Methods After 1 week of adaptive feeding,specific pathogen-free male Mongolian gerbils were randomly assigned to groups and subjected to intragastric administration of Hp,BaP,and Hp+BaP for model induction.At week 32 post model establishment,therapeutic L.salivarius Li01 was administered intragastrically.At week 36,peripheral blood samples were collected from each group for the comet assay,while liver tissues were collected and tested for Cyp1a1 gene expression levels.Results Compared with those in the control group,the comet tail length,％tail DNA,and hepatic Cyp1a1 expression levels were significantly increased in the Hp,BaP,and Hp+BaP groups(P＜0.0001).Among these,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly higher in the Hp+BaP group than in the Hp and BaP groups(P＜0.05).Following intervention with L.salivarius Li01,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly reduced in each group(P＜0.001).Conclusions Hp infection,BaP exposure,and the Hp+BaP combination induced DNA damage in the peripheral lymphocytes of Mongolian gerbils,with the Hp+BaP combination showing synergistic damage.L.salivarius Li01 had a protective effect against DNA damage caused by Hp,BaP,and Hp+BaP.

Objective:To explore any effect of combining Liuzijue training with pulmonary rehabilitation training on functional recovery after pulmonary nodule resection.Methods:Sixty patients after pulmonary nodule resection were randomly divided into an observation group and a control group, each of 30.Both groups were given pulmonary rehabilitation training, but the observation group also received Liuzijue training for 4 weeks. Before and after the treatment and at follow-up 3 months after the surgery, both groups′ forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were evaluated. Exercise endurance and somatic functioning were quantified using the 6-minute walk test (6MWT) and the short physical performance battery (SPPB), respectively. The 36-item short form survey (SF-36) was administered to assess their life quality.Results:After 4 weeks the pulmonary function index, 6-minute walking distance, SPPB scores and SF-36 scores of both groups were significantly improved. Both groups′ improvements had persisted 2 months later. The observation group′s average FVC and FEV1 values, as well as their average scores on some components of the SF-36 instrument were significantly better than the control group′s averages after 4 weeks. After 3 months their average 6MWT distance and SPPB score was also significantly better.Conclusions:Combining Liuzijue training with pulmonary rehabilitation training can significantly improve the pulmonary function of patients after pulmonary nodule resection. It can further improve their exercise endurance, somatic function and life quality. The combination is worthy of clinical promotion and application.

Objective To investigate the protective effects of Ligilactobacillus salivarius Li01(L.salivarius Li01)against DNA damage induced by Helicobacter pylori(Hp),Benzo(a)pyrene(BaP),and Hp+BaP,and to evaluate the probiotic properties of L.salivarius Li01.Methods After 1 week of adaptive feeding,specific pathogen-free male Mongolian gerbils were randomly assigned to groups and subjected to intragastric administration of Hp,BaP,and Hp+BaP for model induction.At week 32 post model establishment,therapeutic L.salivarius Li01 was administered intragastrically.At week 36,peripheral blood samples were collected from each group for the comet assay,while liver tissues were collected and tested for Cyp1a1 gene expression levels.Results Compared with those in the control group,the comet tail length,％tail DNA,and hepatic Cyp1a1 expression levels were significantly increased in the Hp,BaP,and Hp+BaP groups(P＜0.0001).Among these,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly higher in the Hp+BaP group than in the Hp and BaP groups(P＜0.05).Following intervention with L.salivarius Li01,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly reduced in each group(P＜0.001).Conclusions Hp infection,BaP exposure,and the Hp+BaP combination induced DNA damage in the peripheral lymphocytes of Mongolian gerbils,with the Hp+BaP combination showing synergistic damage.L.salivarius Li01 had a protective effect against DNA damage caused by Hp,BaP,and Hp+BaP.

Objective:To explore any effect of combining Liuzijue training with pulmonary rehabilitation training on functional recovery after pulmonary nodule resection.Methods:Sixty patients after pulmonary nodule resection were randomly divided into an observation group and a control group, each of 30.Both groups were given pulmonary rehabilitation training, but the observation group also received Liuzijue training for 4 weeks. Before and after the treatment and at follow-up 3 months after the surgery, both groups′ forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were evaluated. Exercise endurance and somatic functioning were quantified using the 6-minute walk test (6MWT) and the short physical performance battery (SPPB), respectively. The 36-item short form survey (SF-36) was administered to assess their life quality.Results:After 4 weeks the pulmonary function index, 6-minute walking distance, SPPB scores and SF-36 scores of both groups were significantly improved. Both groups′ improvements had persisted 2 months later. The observation group′s average FVC and FEV1 values, as well as their average scores on some components of the SF-36 instrument were significantly better than the control group′s averages after 4 weeks. After 3 months their average 6MWT distance and SPPB score was also significantly better.Conclusions:Combining Liuzijue training with pulmonary rehabilitation training can significantly improve the pulmonary function of patients after pulmonary nodule resection. It can further improve their exercise endurance, somatic function and life quality. The combination is worthy of clinical promotion and application.

【Objective】 To compare the value of CT pulmonary angiography (CTPA) and echocardiography in predicting the degree pulmonary hypertension (PH). 【Methods】 Fifty-four patients in our hospital who underwent right heart catheterization, CTPA and echocardiography for suspected or confirmed PH from November 2013 to April 2021 were retrospectively recruited. Pulmonary artery systolic pressure (PASP) and mean pulmonary artery pressure (PAMP) were measured by right heart catheterization. According to PAMP, the patients were divided into non-PH group and mild, moderate, and severe PH groups. The three-dimensional model of the pulmonary artery was obtained by computer-aided segmentation, and the best fitting circle diameter (Dfit), inscribed circle diameter (Dmin), circumscribed circle diameter (Dmax), hydraulic diameter (Dh), cross-sectional area (Area), circumference (Scf), and the largest area and largest short diameter of the right ventricle were measured. Echocardiography was used to estimate PASP. The differences in the above parameters between different PH groups were compared, the correlations of the above parameters with PASP and PAMP were analyzed, and statistically significant indicators were included to establish three predictive models of PAMP (Model 1: CTPA pulmonary artery; Model 2: CTPA pulmonary artery+CTPA right ventricle; Model 3: CTPA pulmonary artery+CTPA right ventricle+echocardiography), and receiver operating characteristic (ROC) curves were used to compare the diagnostic performance of the three models. 【Results】 Some parameters of main pulmonary artery (Dfit, Dmin, Dmax, Dh, Area, Scf), right pulmonary artery (Dmax, Dh, Area, Scf), left pulmonary artery (Dfit), and right ventricular short diameter increased with the increase of PAMP (P<0.05). Dfit, Dmin, Dh, and area of main pulmonary artery, right pulmonary artery and left pulmonary artery were positively correlated with PASP and PAMP (P<0.05). Right ventricular short diameter and right ventricular maximum area were positively correlated with PASP (P<0.05), and right ventricular short diameter was positively correlated with PAMP (P<0.05). The estimated value of pulmonary artery systolic blood pressure in echocardiography was positively correlated with PASP and PAMP (P<0.05). Model 1, Model 2 and Model 3 could all be used to identify mild PH and moderate PH, among which Model 3 had the best performance in identifying non-PH and mild PH, moderate PH and severe PH. 【Conclusion】 CTPA and echocardiography are helpful in assessing the degree of PH, and the combination of the two has better accuracy in distinguishing non-PH from mild PH, moderate and severe PH.

ObjectiveTo explore the histological characteristics of the kidney in Mongolian gerbils of different ages. MethodsTen Mongolian gerbils of 2, 6, and 12 months old (half male and half female) were selected. After euthanasia, the kidneys were taken and paraffin sections were made. After HE, MASSON and PAS staining, the structural differences of different parts of the kidney tissue in gerbils of different ages were observed by digital scanning, and the relevant data of the kidney tissue were measured by image analysis software. ResultsThe number of proximal convoluted tubules was more than that of distal convoluted tubules in the renal cortex and outer medulla of gerbils. With age, the glomerular density decreased, the glomerular diameter increased, the basement membrane of renal tubules thickened, and the fibrous components between renal tubules increased. ConclusionThe histological structure of Mongolian gerbil's kidney varies with age, which may be related to glomerulosclerosis and parenchymal cell reduction. The specific mechanism needs further study.

Objective Cysteinyl leukotrienes are potent inflammatory mediators. Their actions are mediated by specific receptors,the CysLT receptors(CysLT1R and CysLT2R),which have been cloned and characterized. In this stud-y,we investigated the protective effects of the CysLTR antagonist Pranlukast and HAMI 3379 on global cerebral ischemia/reperfusion(CI/R)injury in gerbils and its underlying mechanisms. Methods The gerbil model of CI/R was established by bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion. Then the animals were equally ran-domized into four groups: sham, model, Pranlukast(0.1 mg/kg)and HAMI 3379(0.1 mg/kg)groups. The later two groups were treated with intraperitoneal injection of Pranlukast and HAMI 3379,respectively,once daily for 4 days before carotid artery occlusion,while the former two groups with saline only,all at 10 mL/kg. After 24 h reperfusion,neurologi-cal deficit scores were observed and the behavioral dysfunction was assessed. The neuron morphology of cerebral cortex and CA1 subregion of hippocampus were observed in brain sections stained with cresyl violet. The expression of autophagy-relat-ed proteins beclin-1 and LC3 in the homogenate of cerebral cortex and hippocampus were determined using western blotting analysis. The ultrastructure of autophagosomes in the CA1 subregion of hippocampus was observed by electron microscopy. Results Compared with the model group, Pranlukast and HAMI 3379 attenuated neurological deficits, improved the be-havioral dysfunction,inhibited the neuron injury and loss, decreased the expression of autophagy-related protein beclin-1 and LC3 and the number of autophagosomes. Conclusions cysteinyl Leukotriene receptor antagonist Pranlukast and HAMI 3379 can alleviate global cerebral ischemia/reperfusion injury in gerbils. The protective effects of Pranlukast and HAMI 3379 appear to be associated with the inhibition of autophagy.