Long non-coding RNAs(lncRNAs),a group of non-coding RNAs with lengths exceeding 200 nucleotides,play a crucial role in the human transcriptome,particularly in various types of cancers,where they are pivotal in regulating the tumor immune microenvironment and tumor cell immune evasion.However,there is currently a lack of systematic literature review.Myeloid-derived suppressor cells(MDSCs),a subset of myeloid cells with immunosuppressive functions,play a significant role in cancer by directly and indirectly suppressing T cell activity,promoting the expansion of regulatory T cells,modulating the tumor microenvironment,and facilitating tumor metastasis.This review emphasizes the importance of in-depth investigation into the regulatory mechanisms of MDSCs for the discovery of effective tumor therapeutic targets and the development of novel treatment strategies.With further understanding and research into the relationship between lncRNAs and MDSCs,it is anticipated that more targets and new therapeutic approaches will be identified for cancer treatment,thereby improving clinical outcomes for patients.

Objective To investigate the mechanism of metformin for regulating tumor-stromal cell cross-talk in breast cancer.Methods Tumor associated fibroblasts(CAFs)co-cultured with breast cancer cells were treated with metformin,and the changes in expressions of hypoxia-inducible factor-1α(HIF-1α),p-AMPK,stroma-derived factor-1(SDF-1)and interleukin-8(IL-8)in the CAFs were detected using ELISA,RT-qPCR or Western blotting;Transwell assay was used to evaluate the invasiveness of the tumor cells and its changes following treatment with exogenous SDF-1,IL-8 and TGF-β1.The effects of HIF-1α shRNA or overexpression plasmid,AMPK shRNA,and treatment with OG(a proline hydroxylase inhibitor)or 2-OXO(a proline hydroxylase activator)were examined on p-AMPK,HIF-1α,SDF-1 and IL-8 expressions and invasiveness of the CAFs.Results Metformin treatment significantly increased the expression levels of p-AMPK,SDF-1 and IL-8(P<0.05)and decreased HIF-1α expression(P<0.05)without affecting AMPK expression level(P>0.05)in the CAFs.The invasion ability of metformin-treated breast cancer cells was significantly decreased(P<0.05).Exogenous SDF-1 and IL-8,HIF-1α overexpression,and OG-induced upregulation of HIF-1α all significantly attenuated the inhibitory effects of metformin on breast cancer cell invasion(P<0.05)and HIF-1α,SDF-1 and IL-8 expressions in CAFs(P<0.05).Transfection with HIF-1α shRNA or treatment with 2-OXO significantly decreased the invasiveness of breast cancer cells(P<0.05).P-AMPK knockdown significantly suppressed the inhibitory effect of metformin on HIF-1α expression in CAFs and on invasion of breast cancer cells(P<0.05).Treatment with TGF-β1 partially decreased the inhibitory effect of metformin on HIF-1α expression in CAFs and invasiveness of the breast cancer cells(P<0.05).Conclusion Metformin suppresses HIF-1α expression in CAFs to block tumor-stromal cross talk in breast cancer.

Objective To investigate the mechanism of metformin for regulating tumor-stromal cell cross-talk in breast cancer.Methods Tumor associated fibroblasts(CAFs)co-cultured with breast cancer cells were treated with metformin,and the changes in expressions of hypoxia-inducible factor-1α(HIF-1α),p-AMPK,stroma-derived factor-1(SDF-1)and interleukin-8(IL-8)in the CAFs were detected using ELISA,RT-qPCR or Western blotting;Transwell assay was used to evaluate the invasiveness of the tumor cells and its changes following treatment with exogenous SDF-1,IL-8 and TGF-β1.The effects of HIF-1α shRNA or overexpression plasmid,AMPK shRNA,and treatment with OG(a proline hydroxylase inhibitor)or 2-OXO(a proline hydroxylase activator)were examined on p-AMPK,HIF-1α,SDF-1 and IL-8 expressions and invasiveness of the CAFs.Results Metformin treatment significantly increased the expression levels of p-AMPK,SDF-1 and IL-8(P<0.05)and decreased HIF-1α expression(P<0.05)without affecting AMPK expression level(P>0.05)in the CAFs.The invasion ability of metformin-treated breast cancer cells was significantly decreased(P<0.05).Exogenous SDF-1 and IL-8,HIF-1α overexpression,and OG-induced upregulation of HIF-1α all significantly attenuated the inhibitory effects of metformin on breast cancer cell invasion(P<0.05)and HIF-1α,SDF-1 and IL-8 expressions in CAFs(P<0.05).Transfection with HIF-1α shRNA or treatment with 2-OXO significantly decreased the invasiveness of breast cancer cells(P<0.05).P-AMPK knockdown significantly suppressed the inhibitory effect of metformin on HIF-1α expression in CAFs and on invasion of breast cancer cells(P<0.05).Treatment with TGF-β1 partially decreased the inhibitory effect of metformin on HIF-1α expression in CAFs and invasiveness of the breast cancer cells(P<0.05).Conclusion Metformin suppresses HIF-1α expression in CAFs to block tumor-stromal cross talk in breast cancer.

The disorder of group 3 innate lymphoid cells(ILC3)subgroup,such as the predominance of NCR-ILC3 but the deple-tion of NCR+ILC3,is unfavorable to damaged intestinal barrier repair,which leads to the prolongations and obstinacy of ulcerative colitis(UC).Our previous studies had shown that luteolin promoted NCRILC3 differentitating into NCR+ILC3 to improving the de-pletion of NCR+ILC3 in UC mice,while the mechanism is unclear.This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3.UC mice model was established with 2％DSS and Notch signaling was blocked,then luteolin was used to intervene.The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice,including inhibit-ing the weight loss,reducing the pathological damage of colon mucosa,etc.,was diminished with blocking Notch signaling pathway.In addition,luteolin increased the proportion of NCR+ILC3,NCR+MNK3 and IL-22+ILC3,decreased intestinal permeability,pro-moted mucin secretion,and promoted ZO-1 and Occludin expression,the above effect of luteolin was neutralized by Notch inhibitor LY-411575.Luteolin activated the abnormally blocked Notch signaling pathway in UC mice.And molecular docking predicted the af-finity of luteolin for RBPJ to be-7.5 kcal·mol-1 in mouse,respectively;the affinity of luteolin for Notchl and RBPJ was respectively scored to be-6.4 kcal·mol-1 and-7.7 kcal·mol-1 homo sapiens.These results proved that luteolin is positive for enhancing the propor-tion of NCR+ILC3 via Notch signaling,and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alle-viating ulcerative colitis.

Objective To evaluate the effect of hypothermic machine perfusion (HMP) on the expression levels of inflammatory cytokines in rat kidney. Methods Thirty male rats were randomly divided into the control (Control group), static cold storage group (SCS group) and HMP group, with 10 rats in each group. The velocity, intrarenal resistance and pH value of perfusion effluent were recorded during HMP. The expression levels of CXC chemokine ligand (CXCL)1, CXCL2, interferon (IFN)-β1, IFN-α4, CC chemokine ligand (CCL)2, CCL20, interleukin (IL)-17α, IL-17C and tumor necrosis factor (TNF)-α messenger RNA (mRNA) in renal tissues were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Pathological changes of the kidney were observed by hematoxylin-eosin (HE) staining. Results During HMP, the velocity and intrarenal resistance remained stable, and the pH value of perfusion effluent was decreased slowly. RT-PCR showed that the relative expression levels of CXCL1, CXCL2, CCL2, CCL20, IL-17α, IL-17C and TNF-α mRNA in the SCS and HMP groups were higher compared with those in the Control group. Compared with the SCS group, the relative expression levels of CXCL1, CXCL2, CCL2, CCL20, IL-17α and TNF-α mRNA were up-regulated in the HMP group (all P<0.05). HE staining revealed that the morphology of renal cells was normal in the Control group, whereas evident epithelial necrosis, cytoplasmic vacuolation, brush border loss and epithelial shedding were observed in the SCS group. Compared with the SCS group, pathological changes in the HMP group were alleviated. Conclusions HMP may activate renal inflammation, and inhibiting the activation of inflammation during HMP is expected to further improve the effect of allograft preservation.

Objective:To explore the effects of different concentrations of 2-hydroxybenzylamine(2-HOBA)on atherosclerosis and vascular smooth muscle cell senescence and the underlying mechanisms.Methods:Fourteen apolipoprotein E-deficient(ApoE-/-)mice were used to establish an atherosclerosis model and were divided into two groups(n=7)using the random number method: a high-fat diet(HD)group and a high-fat diet plus 2-HOBA(1 mg/ml)(HD+ HOBA)group.Pulse wave velocity was used to assess vascular stiffness and a treadmill was used to assess exercise endurance.Oil Red O staining was used to detect the size and number of atherosclerotic plaques.Masson staining was used to detect the morphology of collagen fibers and elastic fibers in the plaque, the size of the necrotic core area of the plaque, and the thickness of the fibrous cap.Mouse smooth muscle cells were treated with different concentrations of 2-HOBA(100 μmol/L, 250 μmol/L and 500 μmol/L)to establish an H 2O 2-induced senescence model.Senescence-associated β-galactosidase staining was used to detect cell senescence.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expression levels of senescence-related secretory phenotype factors, and Western blot was used to detect the expression levels of senescence-related signaling proteins. Results:Compared with the HD group, the HD+ HOBA group showed that the area and number of aortic atherosclerotic plaques were decreased, and the atherosclerotic plaques were stabilized.In addition, compared with the HD group, vascular stiffness in the HD+ 2-HOBA group decreased by 26%(2.59±0.32 mm/ms vs.3.50±0.28 mm/ms), with a statistically significant difference( P<0.01), and exercise endurance increased by 62%[(143.74±24.25)m vs.(233.50±30.21)m, P<0.01], suggesting that 2-HOBA was able to improve aortic vascular stiffness and exercise endurance in mice.2-HOBA ameliorated H 2O 2-induced vascular smooth muscle cell senescence and decreased the mRNA levels of H 2O 2-induced senescence-associated secretory phenotype factors such as interleukin-1β, interleukin-6, tumor necrosis factor-α and monocyte chemoattractant protein-1.Meanwhile, 2-HOBA also inhibited the expression of p53 and p21, the key signaling factors of senescence. Conclusions:2-HOBA suppresses the development and progression of atherosclerosis through inhibiting oxidative stress-related p53/p21 signaling activation and ameliorating vascular smooth muscle cell senescence and the aging-related inflammatory phenotype.

OBJECTIVES: This study aimed to analyze the application value of a modified tragus edge incision and transmasseteric anteroparotid approach to condyle reconstruction. METHODS: Condyle reconstruction was performed in 16 patients (9 females and 7 males) with modified tragus edge incision and transmasseteric anteroparotid approach. After regular follow-up, the function of condyle reconstruction was evaluated by clinical indicators, such as parotid salivary fistula, facial nerve function, mouth opening, occlusal relationship, and facial scar. The morphology of rib graft rib cartilage was evaluated by imaging indicators, such as panoramic radiography, CT, and three-dimensional CT image reconstruction. RESULTS: At 6-36 months postoperative follow-up, all patients had good recovery of facial appearance, concealed incisional scar, no parotid salivary fistula, good mouth opening, and occlusion. One case had temporary facial paralysis and recovered after treatment. Radiographic evaluation further showed that costochondral graft survived in normal anatomic locations. CONCLUSIONS The modified tragus edge incision and transmasseteric anteroparotid approach can effectively reduce parotid salivary fistula and facial nerve injury in condylar reconstruction. The surgical field was clearly exposed, and the incision scar was concealed without increasing the incidence of other complications. Thus, this approach is worthy of clinical promotion.
Male ; Female ; Humans ; Mandibular Condyle/surgery* ; Cicatrix/surgery* ; Fracture Fixation, Internal/methods* ; Mandibular Fractures/surgery* ; Oral Surgical Procedures/methods* ; Treatment Outcome

Objective:To investigate the efficacy of liposomal doxorubicin intensive preconditioning regimen and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treatment of leukemia.Methods:The data of 20 patients with intensive preconditioning regimen allo-HSCT who were admitted to Shenzhen Second People's Hospital from January 2016 to June 2017 were retrospectively analyzed. The transplantation effect, occurrence of complications and prognosis of patients were analyzed.Results:The median time of granulocyte engraftment was 17 d (13-23 d); the median time of platelet engraftment was 22.5 d (minimum 13 d, maximum >90 d). The acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 2 cases and 1 case, respectively. Eight cases occurred hemorrhagic cystitis, 15 cases occurred Epstein-Barr viremia, 8 cases occurred cytomegaloviremia, 1 case occurred sepsis, 1 case occurred acute liver injury, and 2 cases occurred fungal pneumonia. The median follow-up time was 31.7 months (0.8-53.8 months). One patient died of intracranial infection on the 25th day after transplantation; 3 patients relapsed during the follow-up period, and 2 of them died; the other 16 patients carried 100% donor genes during the follow-up period.Conclusions:The liposomal doxorubicin intensive preconditioning regimen and allo-HSCT have a good effect on leukemia. Increasing the intensity of pretreatment does not increase the treatment-related adverse reactions. The incidence rates of Epstein-Barr viremia and cytomegaloviremia are high, but they are improved after active treatment.

OBJECTIVE To evaluate th e effects of comprehensive drug cost control in China ，and to provide reference for further improving the effects of cost control. METHODS Entropy method was used to establish a comprehensive evaluation index system of the comprehensive drug cost control effect from the respective of drug price control ability ，drug cost control ability and patient affordability. The comprehensively evaluate the effects of drug cost control in 31 provinces （autonomous regions and municipalities）during 2016-2020. The k-means cluster method was used to analyze the effects of comprehensive drug cost control in various provinces. RESULTS & CONCLUSIONS During the period of 2016-2020，the total score of comprehensive drug cost control effect of 31 provinces were 14.64，16.71，17.58，17.57，17.88，respectively. The results of cluster analysis were similar to the ranking of entropy method. Medical and health system reform policy had entered a stable period after achieving phased results ； the effects of comprehensive drug cost control was characterized by regional steps in 31 provinces；the effects of comprehensive drug cost control were better in developed coastal areas and some provinces and cities of western regions ，followed by provinces and cities in central China ；however，comprehensive drug cost control in 3 provinces of northeast China showed poor effect. The effects of comprehensive drug cost control in pilot cities of comprehensive medical reform were significantly improved. It is suggested that the successful experience of pilot cities of comprehensive medical reform should be promoted nationwide ，and policies such as volume-based drug procurement ，medical insurance drug price negotiation ，and diagnosis-related groups / diagnosis-intervention packet payment method reform should be further deepened.

Objective:To observe the short-term efficacy of 3D-printed custom-made hemipelvic prosthesis in the treatment of primary malignant bone tumors of the pubis.Methods:From June 2017 to May 2019, a total of 5 patients with pubic primary malignant tumor received type Ⅲ hemipelvectomy and reconstruction with a 3D-printed custom-made hemipelvic prosthesis at Department of Orthopedics, West China Hospital. They were 3 males and 2 females with an average age of 36.3 years (range, from 26 to 46 years). Of them, 3 underwent resection of the upper pubic ramus and 2 resection of both pubic rami. All their tumors were chondrosarcomas, with one case of Enneking stage Ⅱa and 4 cases of Enneking stage Ⅱb. Preoperative CT/MRI image fusion was used to determine the tumor-free resection margin, design guide templates for osteotomy and prosthesis, and simulate surgical procedures. A total of 5 3D-printed custom-made hemipelvic prostheses were designed, including 3 ones with an intramedullary stem to preserve partial pubis and 2 ones with a non-intramedullary stem not to preserve the pubis. The functional recovery was assessed by Musculoskeletal Tumor Society (MSTS) scores. The prosthetic position and osseointegration were evaluated by imaging examination. Oncological outcomes and complications were recorded.Results:R0 resection and precise reconstruction were accomplished in all patients. Their intraoperative blood loss ranged from 300 to 3, 700 mL (mean, 1, 680 mL), operation time from 180 to 430 min (mean, 294 min), and follow-up time from 13 to 29 months (mean, 20.6 months). All the 5 patients were alive with no evidence of disease or tumor recurrence. The functional MSTS scores at the final follow-up ranged from 29 to 31 (mean, 29.8). One male patient complained of erectile dysfunction. Fretting wear around the prosthetic stem was found in 3 patients while bone wear on the normal pubic side in 2. Osseointegration was observed in all patients with no complications like deep infection, prosthesis dislocation, prosthetic or screw breakage.Conclusion:Since 3D-printed custom-made hemipelvic prostheses can result in fine short-term efficacy for pubic primary malignant bone tumors, they may be a reliable method to reconstruct pelvic malignant tumors.