Diabetic kidney disease(DKD)is one of the most important complications of diabetes.In recent years,domestic and foreign studies have found that mammalian target protein of rapamycin(mTOR)related signaling pathway is a classic pathway involved in the regulation of autophagy,which can achieve the therapeutic effect of DKD by targeting the autophagy pathway,and plays a crucial role in the prevention and treatment of DKD.In this paper,we reviewed the mechanism of mTOR-related signaling pathway targeted autophagy in the prevention and treatment of DKD,in order to provide a new reference and basis for clinical prevention and treatment of DKD.

Objective:To explore the efficacy of long intramedullary nails versus short intramedullary nails in the treatment of AO/OTA 31-A3 intertrochanteric fractures.Methods:A retrospective analysis was conducted on 60 patients with AO/OTA 31-A3 intertrochanteric femur fractures treated between March 2019 and August 2022. The patients were randomly divided into two groups (the long nail group and the short nail group). Thirty-four patients were treated with long intramedullary nails, including 16 males and 18 females, aged 68.41±17.84 years old (range 31-96 years). Twenty-six patients were treated with short intramedullary nails, including 13 males and 13 females, aged 72.23±13.97 years old (range 31-90 years). The causes of injury, fracture classification (AO/OTA classification), intraoperative blood loss, operation time, fracture healing time, imaging indexes (fracture reduction quality, postoperative neck trunk angle, and medial support), Harris score of the hip joint at the last follow-up, one-year mortality rates and complications were compared between the two groups.Results:The follow-up time was 24.26±6.67 months in the long nail group and 24.31±5.60 months in the short nail group, and the general information of the two groups were comparable. Between the long nail and short nail group, the intraoperative blood loss was 281.47±235.28 ml vs. 121.92±84.14 ml and the operation time was 110.44±24.63 min vs. 81.15±28.54 min with significant differences ( P<0.05). While the length of hospital stay was 12.35±4.81 d vs. 10.89±4.30 d, the good rate of fracture reduction was 55.9% vs. 61.53%, the fracture healing time was 120.44±16.43 d vs. 128.07±18.33 d, the presence rate of medial support was 67.6% vs. 79.4%, and the excellent rate of Harris score was 65.4% vs. 65.4% with no significant difference between the two groups ( P>0.05). One-year mortality rates was 5.3% vs. 7.1% and complications was 11.7% vs. 15.4% with no significant difference between the two groups ( P>0.05). Conclusion:Both long intramedullary nails and short intramedullary nails are effective in the treatment of AO/OTA 31-A3 intertrochanteric femur fractures. However, surgical time and intraoperative blood loss was less in the short nail group.

Tamoxifen(TAM)has been widely used for the treatment of ER+breast cancer.However,the inevitable emergence of resistance to tamoxifen obstructs the successful treatment of this cancer.The tumor suppressor gene N-myc downstream-regulated gene 2(NDRG2)plays a significant role in the de-velopment of ER+breast cancer.However,it is unclear whether NDRG2 participates in mediating TAM resistance in ER+breast cancer.Here,we investigate the expression of NDRG2 mRNA and protein in TAM-sensitive and TAM-resistant ER+breast cancer cells.The results of immunoblotting experiments re-vealed a negative correlation between NDRG2 expression and TAM resistance ability in ER+breast cancer cells(P＜0.001).CCK-8 cell viability assays and soft agar colony formation assays showed that NDRG2 overexpression in TAM resistant cells significantly reduced the TAM IC50 value and the soft agar colony formation rate(P＜0.001).For the mechanism,the ERAD reporter protein assays showed that NDRG2 overexpression upregulated the expression of the ERAD reporter protein CD3ε-YFP and increased the lev-els of spliced XBP1s mRNA,leading to severe endoplasmic reticulum stress in TAM resistant cells(P＜0.001).Immunoblot analysis confirmed that overexpression of NDRG2 significantly increased the level of phosphorylation of the endoplasmic reticulum stress sensor IRE 1α and the expression levels of its down-stream protein factors,including ERdj4,P58IPK,EDEM and PDIA5(P＜0.001).The in vivo xenograft tumor experiments in mice further verified that NDRG2 overexpression significantly inhibited the growth of resistant tumors,which enhanced the therapeutic effect of TAM(P＜0.001).These findings indicate that increasing NDRG2 expression and triggering severe endoplasmic reticulum stress upon TAM treatment can reverse the resistance of ER+breast cancer cells to TAM and inhibits the growth of ER+breast canc-er tumors.Our results provide valuable new insights and potential targets for improving the clinical man-agement of TAM-resistance and prognosis in ER+breast cancer.

In recent years,the importance of long non-coding RNA(lncRNA)in acute myeloid leukemia(AML)has attracted wide attention.Among them,lncRNAs that play a role in promoting cancer mainly include HOTAIR,UCA1,H19,ITGB2-AS1 and some genes of SNHG family,while in tumor suppression mainly include H22954,NEAT1,SNHG4,LINC01128,etc.This article reviews the role of lncRNAs in the occurrence and development of AML,as well as those related to AML resistance and prognosis assessment,so as to provide a theoretical basis for the diagnosis and prognosis analysis of AML.

Objective:To discover the relationship between the RNF213 gene and acute myeloid leukemia(AML),and explore the effect of RNF213 on the proliferation and apoptosis of THP-1 cells.Methods:Analyze the expression of RNF213 gene in AML and its relationship with prognosis through the GEPIA database.Collecting 30 AML patients and non-tumor hematological patients who went to the Affiliated Hospital of Zunyi Medical University from January 2017 to January 2022.RT-qPCR and Western blot were used to detect the expression levels of RNF213 mRNA and protein.Perform survival of patients was analysed by Kaplan-Meier.Meanwhile,the expression levels of RNF213 mRNA and protein were detected in AML cell lines(THP-1,OCI-AML2).CRISPR-Cas9 was used to knockdown the RNF213 gene in THP-1 cells;flow cytometry was used to detect apoptosis rate of cell.CCK-8 and colony formation assay were used to detect cell proliferation.Western blot was used to detect the expression level of Cleaved-Caspase 3 protein.Results:Compared with the control group,the expression level of RNF213 in AML patients was significantly increased,and patients with high expression of RNF213 have a worse prgnosis.Higher expression level of RNF213 protein in THP-1 cells.After knocking down the RNF213 gene of THP-1 cells,cell proliferation was significantly reduced,and the apoptosis rate and expression of apoptosis related protein Cleared-Caspase3 were significantly increased.Conclusion:AML patients have high expression of RNF213,and the prognosis of high expression patients is poor.The RNF213 gene affects AML cell proliferation and apoptosis,and may be a prognostic marker and potential therapeutic target for AML.

Objective To evaluate clinical efficacy and safety of Bizheng Granules combined with basic therapy in the treatment of liver and kidney insufficiency and phlegm-dampness cross-blocking syndrome of nerve root type cervical spondylosis radiculopathy.Methods Totally 108 patients with nerve root type cervical spondylosis radiculopathy were selected and divided into Bizheng Granules group,Jingfukang Granules group,and Bizheng Granules placebo group according to random number table method,with 36 cases in each group.The three groups were treated with the basic treatment(oral methylcobalamin tablets of 0.5 mg,three times a day,and cervical spine intermittent traction once a day,each time for 15 min),and Bizheng Granules were given in the Bizheng Granules group,and Jingfukang Granules in the Jingfukang Granules group,and Bizheng Granules placebo in the Bizheng Granules placebo group,twice a day after meals.All three groups were treated continuously for 2 weeks and followed up at 4 and 12 weeks after treatment.Visual analog scale(VAS),cervical dysfunction index(NDI),and 36-items short form survey(SF-36)score were recorded in the 3 groups before and after treatment and 4 and 12 weeks after treatment,respectively.Adverse reactions during treatment and follow-up were recorded in the 3 groups.Results 3 cases lost in the Bizheng Granules group,3 cases in the Jingfukang Granules group,and 1 case in the Bizheng Granules placebo group.Compared with the pre-treatment period,the differences in VAS score,NDI score,and SF-36 score among the three groups of patients at all time points of treatment and follow-up were statistically significant(P<0.05).At 12 weeks after treatment,the VAS score and NDI score of the Bizheng Granules group and the Jingfukang Granules group were lower than those of the Bizheng Granules placebo group,but the differences in VAS score and NDI score between Bizheng Granules group and Jingfukang Granules group were not statistically significant(P>0.05).12 weeks after treatment,the SF-36 score of Bizheng Granules group were higher than those of Bizheng Granules placebo group,but the difference in SF-36 score between Bizheng Granules group and Jingfukang Granules group was not statistically significant(P>0.05).The total effective rate of Bizheng Granules group was better than that of the Jingfukang Granules group and Bizheng Granules placebo group(P<0.05).The incidence of adverse reactions in the three groups was not statistically significant(P>0.05).There were no serious adverse events in the three groups.Conclusion Bizheng Granules combined with basic therapy has a definite therapeutic effect in improving pain,restoring cervical dysfunction,and improving quality of life in the treatment of liver and kidney insufficiency and phlegm-dampness cross-blocking syndrome of nerve root type cervical spondylosis radiculopathy,with good safety.

Objective To investigate the diagnostic value of combining carotid intima-media thickness (cIMT) with serum Galectin-3 (Gal-3) and Pentraxin 3 (PTX3) in patients with psoriasis complicated with cardiovascular disease (CVD). Methods Thirty-eight patients with psoriasis complicated with CVD were included in CVD group, 51 patients with psoriasis alone were included in psoriasis group, and 60 healthy subjects were selected as control group. Clinical data were collected from each group. The cIMT was measured using carotid ultrasound, and serum Gal-3, PTX3, and inflammatory markers[high sensitivity C-reactive protein (hs-CRP), procalcitonin (PCT), tumor necrosis factor-α (TNF-α)]were detected using enzyme-linked immunosorbent assay. Multivariate Logistic regression analysis was used to identify the influencing factors of CVD in patients with psoriasis. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of serum Gal-3, PTX3, and cIMT for CVD. Results The cIMT was greater in the CVD group and the psoriasis group than in the control group, and the CVD group was greater than the psoriasis group (P < 0.05). The serum levels of Gal-3, PTX3, hs-CRP, PCT, and TNF-α were higher in the CVD group and the psoriasis group than in the control group, and their levels were higher in the CVD group than in the psoriasis group (P < 0.05). The psoriasis area and severity index (PASI) score was higher in the CVD group than in the psoriasis group (P < 0.05). Pearson's correlation analysis showed that cIMT, Gal-3, and PTX3 were separately positively correlated with hs-CRP, PCT, and TNF-α (P < 0.05). Multivariate Logistic regression analysis showed that PASI score, cIMT, Gal-3, PTX3, hs-CRP, and TNF-α were independent influencing factors for CVD in patients with psoriasis (OR=1.250, 1.451, 1.432, 1.365, 1.413, 1.465; P < 0.05). The diagnostic model based on cIMT combined with serum Gal-3 and PTX3 had higher diagnostic value for CVD in patients with psoriasis than single diagnosis. The area under the curve was 0.922, with sensitivity and specificity of 0.91 and 0.85, respectively. Conclusion The cIMT, serum Gal-3, and serum PTX3 are independent influencing factors for CVD in patients with psoriasis. The combination of the three indicators has higher diagnostic value for CVD in patients with psoriasis.

Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and β-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.
Humans ; Animals ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; B7-H1 Antigen/metabolism* ; Ligands ; Liver Neoplasms/pathology* ; RNA, Small Interfering/metabolism* ; Neoplastic Stem Cells/physiology* ; Cell Line, Tumor ; Cell Proliferation

Objective:To analyze the risk factors of radiation-based sarcopenia in patients with multiple myeloma (MM).Methods:A total of 185 clinical and imaging data of patients with MM admitted to Beijing Chaoyang Hospital from September 2009 to October 2019 were retrospectively analyzed. The area of the erector spinae muscle and the area of fatty infiltration (FI) in the fascial compartment were measured by Image-pro Ρlus software, and the area of the fat-free erector spinae muscle and the fat infiltration rate (FI%) were calculated. Sarcopenia was defined as an erector spinae area of less than 3 197 mm 2 in males and 2 895 mm 2 in females. The differences in gender, age, body mass index, disease duration, hemoglobin, leukocytes, platelets, albumin, serum calcium, lactate dehydrogenase, serum creatinine, alkaline phosphatase, M-protein, serum β 2-microglobulin, bortezomib chemotherapy, receipt of stem cell transplantation, osteopathy, stage, recurrence and progression of MM between the sarcopenia group and the normal muscle group were compared. Binary logistic regression was used to analyze the independent risk factors of sarcopenia in MM patients. Kaplan-Meier curves were drawn to compare the survival rates between the two groups. Results:53.0% (98/185) of MM patients were complicated with sarcopenia: there were 30 males, whose fat-free erector spinae area was 25.0±6.0 cm 2, the FI of erector spinae was 12.0±4.8 cm 2, and the FI% was 31.5%±12.0%, while there were 68 females, whose fat-free erector spinae area was 22.7±4.2 cm 2, the FI of erector spinae was 10.7±4.1 cm 2, and the FI% was 30.2%±9.8%. 47.0% (87/185) of MM patients had normal muscle mass: there were 62 males, whose fat-free erector spinae area was 40.6±6.5 cm 2, the FI of erector spinae was 9.3±4.8 cm 2, and the FI% was 17.9%±7.4%, while there were 25 females, whose fat-free erector spinae area was 33.6±5.1 cm 2, the FI of erector spinae was 9.9±3.0 cm 2, and the FI% was 21.9%±5.7%. There were statistically significant differences in the gender composition ratio (χ 2=30.47, P<0.001), hemoglobin ( t=-2.73, P=0.007), serum creatinine ( Z=-2.26, P=0.024), receipt of stem cell transplantation (χ 2=4.32, P=0.038), and MM recurrence and progression (χ 2=3.85, P=0.050) between the two groups. However, there were no significant differences in age, body mass index, course of disease, leukocytes, platelets, albumin, alkaline phosphatase, lactate dehydrogenase, serum calcium, M-protein, serum β 2-microglobulin, bortezomib chemotherapy, osteopathy or MM stage ( P>0.05). Binary logistic regression analysis showed that female was an independent risk factor for sarcopenia in MM patients. The survival rates at 2, 3, 4, and 5 years were 87.9%, 71.8%, 64.4%, and 53.7% in the sarcopenia group, and 92.1%, 75.8%, 66.8%, and 66.8% in the normal muscle group, respectively, with no statistically significant differences ( HR=0.71, P=0.364). Conclusion:The incidence of radiation-based sarcopenia in MM patients is 53.0%. Low hemoglobin and blood creatinine levels, not receiving stem cell transplantation, and recurrence or progression of MM are associated with sarcopenia in MM patients, and female is an independent risk factor for sarcopenia in MM patients.

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.
Humans ; COVID-19 ; Algorithms ; Databases, Factual ; Prescriptions ; Plant Extracts