Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Gliomas are the most common central nervous system tumours; they are highly aggressive and have a poor prognosis. RGS16 belongs to the regulator of G-protein signalling (RGS) protein family, which plays an important role in promoting various cancers, such as breast cancer, pancreatic cancer, and colorectal cancer. Moreover, previous studies confirmed that let-7c-5p, a well-known microRNA, can act as a tumour suppressor to regulate the progression of various tumours by inhibiting the expression of its target genes. However, whether RGS16 can promote the progression of glioma and whether it is regulated by miR let-7c-5p are still unknown. Here, we confirmed that RGS16 is upregulated in glioma tissues and that high expression of RGS16 is associated with poor survival. Ectopic deletion of RGS16 significantly suppressed glioma cell proliferation and migration both in vitro and in vivo. Moreover, RGS16 was validated as a direct target gene of miR let-7c-5p. The overexpression of miR let-7c-5p obviously downregulated the expression of RGS16, and knocking down miR let-7c-5p had the opposite effect. Thus, we suggest that the suppression of RGS16 by miR let-7c-5p can promote glioma progression and may serve as a potential prognostic biomarker and therapeutic target in glioma.
Humans ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; MicroRNAs/metabolism* ; Glioma/genetics* ; Genes, Tumor Suppressor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor

ObjectiveTo explore the effects of different intensity of wearable lower limb rehabilitation robot-assisted training on walking function, lower limb motor function, balance function and functional independence of stroke patients. MethodsFrom November, 2021 to December, 2022, 60 stroke patients hospitalized in Beijing Bo'ai Hospital were randomly divided into control group (n = 20), observation group 1 (n = 20) and observation group 2 (n = 20). All the groups received routine rehabilitation, while the control group received routine walking training 30 minutes a day, the observation group 1 received wearable lower limb rehabilitation robot-assisted training 30 minutes a day, and the observation group 2 received wearable lower limb rehabilitation robot-assisted training 60 minutes a day, for four weeks. They were assessed with Functional Ambulation Category scale (FAC), Fugl-Meyer Assessment-Lower Extremities (FMA-LE), Berg Balance Scale (BBS) and Rivermead Mobility Index (RMI) before and after treatment. ResultsOne case in the observation group 1 and three cases in the observation group 2 dropped down. The FAC, FMA-LE, BBS and RMI scores improved in all the three groups after treatment (|Z| > 3.448, |t| > 8.102, P < 0.001), and there was no significant difference in all the indexes among the three groups (|H| < 4.643, F = 1.454, P > 0.05); however, the improvement of BBS score was more in the observation group 1 than in the control group (P < 0.05), and the improvement of all the indexes was more in the observation group 2 than in the control group (P < 0.05). ConclusionThe wearable lower limb rehabilitation robot-assisted training may promote the recovery of walking function, lower limb motor function, balance function and functional independence of stroke patients, and high-intensity training seems to be more effective.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

Objectives:This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) .Methods:From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy.Results:The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients.Conclusion:Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

Objective:To screen important genes and characterize their functions and signaling pathways by weighted gene co-expression network analysis (WGCNA) on the gene expression profile of brain tissue after traumatic brain injury (TBI) so as to provide a reference for the mechanism research and treatment of TBI.Methods:The rat TBI gene expression profile GSE2871 was downloaded from the Gene Expression Omnibus (GEO). The expression profile of 8 799 genes of all 47 rat brain tissue samples was analyzed by WGCNA. After calculating and selecting the β-weighted soft threshold, undirected weighted gene network was constructed to identify gene sets with a high degree of correlation. Sample information was obtained from the database to calculate the correlation between each trait of the samples and modules. Gene ontology (GO) analysis and KEGG pathway analysis were performed for the genes in modules related to injury severity and sampling side in order to unvail the biological processes and pathways involved. The gene-module correlation and gene-trait correlation in these key modules were calculated and hub genes were selected.Results:All the rat brain tissue samples and genes in GSE2871 were included in the WGCNA analysis. A total of 22 modules were obtained, which were marked as modules A to V. Modules E, G, T and U were significantly associated with the sampling side. Modules E and G were significantly related to injury severity . GO analysis and KEGG pathway analysis indicated that the genes in modules E and G with significant relation to injury severity and sampling side were mainly implicated in leukocyte migration, cell chemotaxis, various immune response regulation, etc. The involved pathways included antigen processing and presentation pathways, cell factor-cytokine receptor interaction, interleukin-17 signaling pathway, etc. While modules T and U with significant relation to the sampling side were mainly implicated in hypoxia response, cell metabolism, cell membrane ion channel regulation, signal transduction, etc. The pathways involved were neurodegenerative disease signaling pathways, ribosomes, autophagy, neuroactive ligand-receptor interactions, etc. Among the key modules significantly relating to traits, Tuba1b/1c, Ifitm3, Cebpd, Nfkbia, Serinc3, Pmpcb and Cyp4a8 were selected as hub genes of the above key modules.Conclusion:The genes significantly relating to rat TBI are mainly involved in pathophysiological links such as immune activation, inflammatory response, abnormal energy metabolism, calcium channel disorders, abnormal autophagy and cell apoptosis.

Objective:To analyze the efficacy and safety of curcumin in the treatment of knee osteoarthritis.Methods:The randomized controlled trials of curcumin in the treatment of knee osteoarthritis published from January 2011 to August 2021 were retrieved. The bias risk of the included literatures was evaluated by Revman 5.3 software, and the efficacy related indexes and the incidence of adverse events were analyzed by Stata 16.0 software. The weighted mean difference ( WMD) was calculated for the difference of efficacy indexes, the odds ratio ( OR) was calculated for the difference of safety indexes, the difference was compared by t test. Results:① A total of 9 relevant literatures were included, all of which were in English. ② A total of 724 patients were included in the study, of which 383 were treated with curcumin capsules and 341 were treated with placebo. ③ The visual analogue scale/score (VAS) of patients treated with oral curcumin at 3-4, 6 and 8 weeks were significantly lower than those of patients treated with oral placebo, the differences were statistically significant [weighted mean difference ( WMD)=-1.09, 95% CI (-1.44, -0.73), P<0.001; WMD=-1.52, 95% CI (-2.35, -0.69), P<0.001; WMD=-1.20, 95% CI(-1.71, -0.69), P<0.001]. ④ The western Ontario and McMaster universities osteoarthritis index (WOMAC) scores of patients treated with oral curcumin for 3-4 and 6-8 weeks were significantly lower than those of patients treated with oral placebo, and the differences were statistically significant [ WMD=-7.96, 95% CI(-14.89, -1.04), P=0.020; WMD=-15.34, 95% CI(-20.51, -10.18), P<0.001]. Specifically, the WOMAC pain and stiffness scores of patients treated with oral curcumin for 6-8 weeks were significantly lower than those of patients treated with oral placebo, and the differences were statistically significant [ WMD=-2.16, 95% CI(-3.69, -0.63), P=0.010; WMD=-1.00, 95% CI (-1.54, -0.46), P<0.001]. The WOMAC joint function scores of patients treated with oral curcumin for 3-4 and 6-8 weeks were significantly lower than those of patients treated with oral placebo, the difference was statistically significant [ WMD=-3.21, 95% CI(-4.51, -1.92), P<0.001; WMD=-7.07, 95% CI(-11.19, -2.94), P<0.001]. ⑤ There was no significant difference in the incidence of adverse events between oral curcumin and placebo [ OR=1.19, 95% P(0.74, 1.90), P=0.478]. Conclusion:Compared with placebo, oral curcumin can significantly alleviate the pain, stiffness and joint function of patients with knee osteoarthritis, and its safety is similar to placebo.

Objective:To compare the clinical efficacy and safety of intra-articular injection of platelet rich plasma and hyaluronic acid in the treatment of knee osteoarthritis.Methods:The relevant literatures including the randomized control study of intra-articular injection of platelet rich plasma and hyaluronic acid in the treatment of knee osteoarthritis published from January 2010 to December 2021 were searched. The bias risk of the included literatures was evaluated by Revman 5.3 software, and the data were processed and analyzed by Stata 16.0 software. The weighted mean difference ( WMD) was calculated for the difference ofefficacy indexes, and the difference was compared by t-test. The odds ratio ( OR) was calculated for the difference of safety index, and the difference was compared by t-test. Results:① A total of 10 literatures were included, all of which were in English. ② A total of 921 patients were included in the study, of which 479 patients were treated with intra-articular injection of platelet rich plasma and 442 patients were treated with intra-articular injection of hyaluronic acid. ③ Comparing the VAS scores of platelet rich plasma injection and hyaluronic acid injection, the visual analogue scale (VAS) scores of platelet rich plasma injection patients were significantly lower than those of hyaluronic acid injection patients after 6 and 12 months of injection treatment, and the difference was statistically significant [ WMD(95% CI)=-0.66(-1.25, -0.77), P=0.029; WMD(95% CI)= -0.90(-1.51, -0.29), P=0.004]. ④ The specific performance was that the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score of patients injected with platelet rich plasma after 6 and 12 months of injection treatment was significantly lower than that of patients injected with hyaluronic acid [ WMD(95% CI)=-0.76(-1.06, 0.45), P<0.001; WMD(95% CI)=-1.35(-2.05, -0.65), P<0.01]; After 3, 6 and 12 months of injection treatment, the WOMAC stiffness score of patients injected with platelet rich plasma was significantly lower than that of patients injected with hyaluronic acid [( WMD(95% CI)=-0.37(-0.66, -0.08), P=0.011; WMD(95% CI)=-0.30(-0.57, -0.04), P=0.023; WMD(95% CI)=-0.62(-0.92, -0.33), P<0.001]; After 3, 6 and 12 months of injection treatment, the WOMAC function score of patients injected with platelet rich plasma was significantly lower than that of patients injected with hyaluronic acid [ WMD(95% CI)=-1.90 (-2.53, -1.27), P<0.001; WMD(95% CI)=-5.77(-9.20, -2.34), P=0.001; WMD(95% CI)=-5.72(-8.62, -2.82), P<0.001]. ⑤There was no significant difference in the incidence of adverse events between the two intra-articular injection methods [ OR(95% CI)=1.28(0.68, 2.42), P=0.440]. Conclusion:Compared with intra-articular injection of hyaluronic acid, the short-term clinical efficacy of injection of platelet rich plasma is equivalent to that of injection of hyaluronic acid, but the long-term clinical efficacy is better, and the safety of the two methods is similiar.

Objective:To observe the clinical effect of scraping therapy on lumbar disc herniation (LDH) with different syndromes.Methods:Using the convenient sampling method, a total of 30 non-emergency LDH patients who were admitted to Department of Orthopedics and Traumatology of Yangzhou Hospital of Traditional Chinese Medicine from July 2017 to June 2018 were selected as the research objects. Among them, there were 11 cases of qi stagnation and blood stasis syndrome, 8 cases of damp-heat obstruction syndrome, 7 cases of cold-damp obstruction syndrome and 4 cases of liver and kidney deficiency syndrome. Du meridian, the bladder meridian of Foot Taiyang, as well as Jiaji (EX-B2) in pathological or painful sections, Ashi point, Shenshu (BL 23) , and Weizhong (BL 40) were mainly scraped. The treatment interval is 2~5 days (the marks of scrapping fade) , twice of scrapping as a treatment course and a total of 3 courses involved in the whole treatment. Japanese Orthopaedic Association (JOA) Score, Visual Analogue Scale (VAS) , serum interleukin-1 β (IL-1β) and interleukin-10 (IL-10) were compared before and after scraping.Results:Compared with those before scraping, the JOA score increased, the VAS decreased, the serum IL-1β content decreased and the serum IL-10 content increased after scraping, and the differences were sttaistically significant ( P<0.01) . Among them, the JOA scores of patients with qi stagnation and blood stasis syndrome and cold-damp obstruction syndrome were higher than those of damp-heat obstruction syndrome and liver-kidney deficiency syndrome, and the differences were statistically significant ( P<0.05) . The levels of serum IL-10 in patients with qi stagnation and blood stasis syndrome, damp-heat obstruction syndrome and cold-damp obstruction syndrome were higher than those in patients with liver-kidney deficiency syndrome, and the differences were statistically significant ( P<0.05) . Conclusions:The curative effect of scraping in the treatment of LDH is definite, and the curative effect is better for excessive syndromes.

Objective:To investigate the features of gait disorders in patients with idiopathic normal pressure hydrocephalus(iNPH).Methods:Clinical data of 42 patients diagnosed with iNPH admitted to the neurological department of Aviation General Hospital from March 2017 to July 2020 were consecutively collected.The features of gait disturbance and activity of daily living were retrospectively studied.Results:Of the 42 patients, 29 cases(69%)were males, aged(73.0±8.3)years, and 13 cases were females, aged(73.0±8.3)years old.The mean course of disease was(3.5±3.0)years.There were 90.5% of patients(38/42)complained of gait disorders, and 61.9%(26/42)had fall histories.All patients had gait abnormalities.The time for 3m-Timed Up and Go(TUG)test were(27.8±17.0)seconds, and the proportion of patients with the time for 3m-TUG less than 10 seconds, 10~20 seconds and more than 20 seconds were 5.9%(2/34), 35.3%(12/34)and 58.8%(20/34), respectively.In the 10-meter walking test, 8 patients needed assistance.Of the 34 patients who could walk independently, 94.1%(32/34)had tandem walking disturbed and tendency toward falling, 76.5%(26/34)had turning disturbed, 44.1%(15/34)had wide based stride and small steps, 29.4%(10/34)had trunk balance disturbed, 23.5%(8/34)had reduced foot-floor clearance, and 8.8%(3/34)had start hesitation, 97.6%(41/42)had abnormal step counting and 90.5%(38/42)had abnormal time evaluation.The proportion of patients with activity of daily living(Barthel Index)scores of(mild dependence), moderate dependence and severe dependence were 71.4%(30/42), 28.6%(12/42)and 0%(0/42). Of the 30 patients with mild dependence, 56.7%(17/30)had fall histories.Conclusions:In our study, all patients have gait dysfunction, which causes some impact on activity of daily living and a higher risk of falls.Gait slowness, tandem walking disturbed, turning disturbed, tendency toward falling, wide based stride and small steps are the most involved gait characteristics.Early assessment of gait disorders is of great significance in early diagnosis and the prevention of falls and living ability decline.