MRPL48 is a novel prognostic and predictive biomarker of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent forms of cancer and poses a threat to the health and survival of humans. Mitochondrial ribosomal protein L48 (MRPL48) belongs to the mitochondrial ribosomal protein family, which participates in energy production. Studies have shown that MRPL48 can predict osteosarcoma incidence and prognosis, as well as promotes colorectal cancer progression. However, the role of MRPL48 in HCC remains unknown. METHODS: TCGA, GEO, HCCDB, CPTAC, SMART, UALCAN, Kaplan-Meier plotter, cBioPortal, and MethSurv were performed for bioinformatics purposes. Quantitative RT-PCR, immunoblotting, and functional studies were conducted to validate the methodology in vitro. RESULTS: MRPL48 was greatly overexpressed in HCC tissues, compared with healthy tissue, which was subsequently demonstrated in vitro as well. The survival and regression analyses showed that MRPL48 expression is of significant clinical prognostic value in HCC. The ROC curve and nomogram analysis indicated that MRPL48 is a powerful predictor of HCC. MRPL48 methylation was adversely associated with the expression of MRPL48, and patients with a low level of methylation had poorer overall survival than those with a high level of methylation. GSEA showed that the expression of the MRPL48 was correlated with Resolution of Sister Chromatid Cohesion, Mitotic Prometaphase, Retinoblastoma Gene in Cancer, RHO Gtpases Activate Formins, Mitotic Metaphase and Anaphase, and Cell Cycle Checkpoints. An analysis of immune cell infiltration showed a significant association between MRPL48 and immune cell infiltration subsets, which impacted the survival of HCC patients. Additionally, MRPL48 knockdown reduced HCC cell proliferation, migration, and invasion in vitro. CONCLUSIONS: We demonstrated that MRPL48 expression may be associated with HCC development and prognosis. These findings may open up new research directions and opportunities for the development of HCC treatments.

Isolated traumatic gallbladder injury: A case report.

BACKGROUND: Isolated gallbladder injury (GI) (IGI) directly induced by abdominal trauma is rare. Symptoms, indications, and imaging examinations of IGI are frequently non-specific, posing tremendous diagnostic challenges, which are simple to overlook and may have severe implications. Improving doctors' understanding of gallbladder injury (GI) facilitates early detection and decreases the likelihood of severe consequences, including death. CASE SUMMARY: We report a case of IGI caused by blunt violence (after falling from three meters with the umbilicus as the stress point) and performed laparoscopic repair of the gallbladder rupture, which helps clinicians understand IGI and reduce the severe consequences of delayed diagnosis. Through extensive medical history and dynamic abdominal ultrasound evaluation, doctors can identify GI early and begin surgery, thereby decreasing the devastating repercussions of delayed diagnosis. CONCLUSION: This article aims to improve clinicians' understanding of IGI and propose a method for the diagnosis and treatment of GI.

Mechanistic origin of different binding affinities of SARS-CoV and SARS-CoV-2 spike RBDs to human ACE2

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein mediates viral entry into host cells through binding to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). It has been shown that SARS-CoV-2 RBD (RBDCoV2) has a higher binding affinity to human ACE2 than its highly homologous SARS-CoV RBD (RBDCoV), for which the mechanistic reasons still remain to be elucidated. Here, we used the multiple-replica molecular dynamics (MD) simulations, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations, and interface residue contact network (IRCN) analysis approach to explore the mechanistic origin of different ACE2 binding affinities of these two RBDs. The results demonstrate that, when compared to the RBDCoV2-ACE2 complex, the RBDCoV-ACE2 complex features the enhanced overall structural fluctuations and inter-protein positional movements and increased conformational entropy and diversity. The inter-protein electrostatic attractive interactions are a dominant force in determining the high ACE2 affinities of both RBDs, while the significantly strengthened electrostatic forces of attraction of ACE2 to RBDCoV2 determine the higher ACE2 binding affinity of RBDCoV2 than of RBDCoV. Comprehensive comparative analyses of the residue binding free energy components and IRCNs reveal that, although any RBD residue substitution involved in the charge change can significantly impact the inter-protein electrostatic interaction strength, it is the substitutions at the RBD interface that lead to the overall stronger electrostatic attractive force of RBDCoV2-ACE2, which in turn not only tightens the interface packing and suppresses the dynamics of RBDCoV2-ACE2, but also enhances the ACE2 binding affinity of RBDCoV2 compared to that of RBDCoV. Since the RBD residue substitutions involving gain/loss of the positively/negatively charged residues, in particular those near/at the binding interfaces with the potential to form hydrogen bonds and/or salt bridges with ACE2, can greatly enhance the ACE2 binding affinity, the SARS-CoV-2 variants carrying such mutations should be paid special attention to.

Multi-species hydrocarbon measurement using TDLAS with a wide scanning range DFG laser.

Tunable diode laser absorption spectroscopy (TDLAS) is a widely used diagnostic technique due to its high sensitivity, fast response, low cost, and other merits. Hydrocarbon detection is a field of great interest in the application of tunable diode lasers as hydrocarbons are fundamental molecules in many industrial processes. Many tunable diode lasers are only suitable for single species detection due to the short scanning range and in real situations. However, different hydrocarbon species tend to exist simultaneously. Here we present a laser system based on the difference-frequency generation (DFG) method for simultaneous hydrocarbon mixtures detection. The direct absorption spectra of different hydrocarbons covering various groups (e.g., alkane, olefin, and aromatic) were measured. The measurements of the concentration dependence of absorbance for each molecule were carried out. The R2 values were larger than 0.997, which demonstrated the system can measure hydrocarbons covering different molecular classes accurately. The mixture components were identified using the independent component analysis and quantitative analysis was performed using the classical least-squares method. Future studies will focus on the validation of the system in actual processes.

Indigenous microbiota protects development of medication-related osteonecrosis induced by periapical disease in mice / 国际口腔科学杂志·英文版

Bacterial infection is a common finding in patients, who develop medication-related osteonecrosis of the jaw (MRONJ) by the long-term and/or high-dose use of anti-resorptive agents such as bisphosphonate (BPs). However, pathological role of bacteria in MRONJ development at the early stage remains controversial. Here, we demonstrated that commensal microbiota protects against MRONJ development in the pulp-exposed periapical periodontitis mouse model. C57/BL6 female mice were treated with intragastric broad-spectrum antibiotics for 1 week. Zoledronic acid (ZOL) through intravenous injection and antibiotics in drinking water were administered for throughout the experiment. Pulp was exposed on the left maxillary first molar, then the mice were left for 5 weeks after which bilateral maxillary first molar was extracted and mice were left for additional 3 weeks to heal. All mice were harvested, and cecum, maxilla, and femurs were collected. ONJ development was assessed using μCT and histologic analyses. When antibiotic was treated in mice, these mice had no weight changes, but developed significantly enlarged ceca compared to the control group (CTL mice). Periapical bone resorption prior to the tooth extraction was similarly prevented when treated with antibiotics, which was confirmed by decreased osteoclasts and inflammation. ZOL treatment with pulp exposure significantly increased bone necrosis as determined by empty lacunae and necrotic bone amount. Furthermore, antibiotics treatment could further exacerbate bone necrosis, with increased osteoclast number. Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.

Efficacy and Safety of Cladribine-based Intensified Conditioning Regimen in Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, safety and the risk factors affecting prognosis of high-risk acute myeloid leukemia (AML) patients treated by cladribine-based intensified conditioning regimen.@*METHODS@#The clinical data of 28 patients with high-risk AML treated by cladribine in combination with busulfan plus cyclophosphamide (BuCy) intensified conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Zhujiang Hospital, Southern Medical University from October 2016 to June 2020 were analyzed retrospectively. The overall survival (OS) rate, cumulative progression-free survival (PFS) rate, relapse rate, non-relapse mortality (NRM), regimen related toxicity (RRT) and risk factors affecting prognosis of the patients were analyzed.@*RESULTS@#The 1-year OS and PFS of the patients after implantation was (78.8±8.6)% and (79.8±8.1)%, while the 1-year cumulative relapse rate and NRM of the patients was 9.3% and 22.0%, respectively. The 1-year expected OS of MRD- high-risk patients before HSCT was 100%. The 1-year expected OS and PFS of the patients in pre-transplant relapse group was (46.9±18.7)% and (50.0±17.7)%, respectively. The incidence of I/II grade RRT was 39.3%. NO III/IV grade RRT were found in 28 patients. Multivariate analysis showed that pre-transplant relapse was the independent risk factor affecting OS and PFS of the patients.@*CONCLUSION@#The intensified conditioning regimen of cladribine in combination with BuCy can reduce the relapse rate of high-risk AML transplantation, and its RRT is mild, exhibiting good safety. MRD- high-risk patients before HSCT can achieve better transplant benefits, but the prognosis of patients with relapse before transplantation is not significantly improved. Therefore, for non-relapsed high-risk AML patients, this intensified conditioning regimen deserves to be considered.

Characteristics of blood test indexes in patients with pneumoconiosis complicated with tuberculosis / 环境与职业医学

Background The positive rate of sputum bacteria in patients with pneumoconiosis complicated with pulmonary tuberculosis is lower than that in patients with simple tuberculosis, which makes the disease assessment more difficult. Objective To compare the differences of blood test indexes between patients with pneumoconiosis complicated with bacteriologically negative and bacteriologically positive pulmonary tuberculosis, so as to provide a basis for the assessment of lesions in patients with pneumoconiosis complicated with pulmonary tuberculosis. Methods The relevant information of 329 patients with pneumoconiosis complicated with tuberculosis diagnosed from 2010 to 2020 was retrospectively collected, including 260 cases of pneumoconiosis complicated with bacteriologically negative tuberculosis (B-TB) and 69 cases of pneumoconiosis complicated with bacteriologically positive tuberculosis (B+TB). The demographic characteristics and blood test indexes of the two groups of patients were analyzed and compared, and logistic regression analysis was conducted to identify factors associated with pneumoconiosis complicated with bacteriologically positive tuberculosis. Results Body mass index (BMI) was significantly different between the two groups (P<0.05), and the proportion of BMI≤18.5 kg·m−2 in the pneumoconiosis cases with B+TB was higher than those with B-TB. The levels of platelet count, fibrinogen, white blood cell count, neutrophil count, monocyte count, C-reactive protein, erythrocyte sedimentation rate, and D-dimer in the pneumoconiosis cases with B+TB were higher than those in the pneumoconiosis cases with B-TB (P<0.05); the levels of mean platelet volume, hemoglobin, albumin to globulin ratio, and high-density lipoprotein in the pneumoconiosis with B+TB group were lower than that in the pneumoconiosis with B-TB group (P<0.05). The abnormal rates of other indicators except mean platelet volume, fibrinogen, and high-density lipoprotein were higher in the pneumoconiosis with B+TB group than in the pneumoconiosis with B-TB group (P<0.05). The results of multiple logistic regression showed that C-reactive protein (OR=1.006, 95%CI: 1.001-1.010), platelet count (OR=1.004, 95%CI: 1.002-1.007), and monocyte count (OR=3.461, 95%CI: 1.370-8.745) were associated with positive sputum smear in patients with pneumoconiosis complicated with pulmonary tuberculosis (P<0.05). Conclusion Some blood test indexes show differences between pneumoconiosis complicated with bacteriologically positive patients and pneumoconiosis complicated with bacteriologically-negative tuberculosis patients. C-reactive protein, platelet count, and monocyte count are factors associated with sputum positivity in pneumoconiosis complicated with tuberculosis patients. Monitoring selected indicators of blood test have a certain reference value for the assessment of lesions in patients with pneumoconiosis complicated with tuberculosis.

Analysis of occupational identity among family doctor teams and its influencing factors in Chengdu / 环境与职业医学

Background The contracted family doctor services are the embodiment of the implementation of the new medical reform policy, and the transformation of the grass-roots health service mode. Studies have proved that the occupational stress in medical staff was at a high level. The enhancement of professional identity will contribute to strengthen team building，alleviate job burnout, and reduce turnover intention of family doctors. Objective To investigate the current situation of occupational identity among family doctor teams in Chengdu, to examine potential influencing factors of occupational identity, and to provide a reference for promoting career development and team building of family doctor teams. Methods Multi-stage random cluster sampling was adopted to enroll study participants form 46 primary healthcare centers where family doctor contract services were implemented among 23 districts and counties in Chengdu between March 4 and 26, 2021. A total of 2 681 family doctors participated in this survey. A self-reported survey was conducted to collect participants' demographic and occupational data. The Effort-Reward Imbalance (ERI）questionnaire was implemented to assess occupational stress. The Professional Identity Scale was used to appraise occupational identity. Results A total of 2 327 valid questionnaires were collected, with a valid recovery rate of 86.80%, involving 1 715 females (73.7%) and 612 males (26.3%), with dominant age groups of 26−35 years (43.3%) and 36−45 years (30.4%), a high proportion of being married (82.8%), having college (36.0%) and undergraduate (47.3%) education, a high proportion of primary titles (66.0%) and informal work contract (66.1%). About 88.7% of family doctor team workers reported occupational stress. The average score of occupational identity was (3.68±0.62) points. There were significant differences in occupational identity scores among different professional title, work contract, working years in medical institutions, income, and effort/reward ratio (EER) groups (P < 0.05). ERR was negatively correlated with occupational identity (rs=−0.495, P<0.05）. The multiple regression model showed that occupational identity score in the non-staffed participants was lower than the score in the staffed ones (OR=0.429, 95%CI: 0.299−0.825). The occupational identity score in the participants having associate senior title or above was higher than in without professional title (OR=1.424, 95%CI: 1.194−2.328). The longer the working years, the higher the occupational identity score among the participants. The score of the more than 20 working years group was 1.820 times that of the less than 5 working years group (95%CI: 1.342−2.543). The higher the income, the higher the occupational identity score. The score of the 9001−12000 yuan per month group was 1.977 times that of the 1000−3000 yuan per month group (95%CI: 0.811−9.696) , and the score of the more than 12000 yuan per month group was 2.283 times that of the 1000−3000 yuan per month group (95%CI: 1.199−10.267）. Conclusion The family doctor team workers generally report occupational stress, and their occupational identity is at a medium level in Chengdu. Relevant managers should implement intervention measures against the main influencing factors to reduce their work tension and improve their occupational identity.

The mechanism of tilianin against ischemia-reperfusion injury of H9c2 cells / 药学学报

Z-VAD-FMK was combined with hypoxia-reoxygenation (H/R) injury to establish a necroptosis model of H9c2 cells to mimic the pathological changes of myocardial ischemia reperfusion injury (MIRI) in vitro and to study the effect and mechanism of tilianin against myocardial ischemia-reperfusion injury. A cell counting kit-8 (CCK-8) was used to detect cell viability, and commercial kits were used to detect lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in the cell culture supernatant. Hoechst 33342/PI immunofluorescence staining was used to detect cell death. DCFH-DA, BBcellProbeTMM61, and JC-1 probes were used to detect reactive oxygen species (ROS), mitochondrial permeability transition pore (mPTP), and mitochondrial membrane potential (MMP), respectively. An enzyme-linked immunosorbent assay (ELISA) method was used to detect the release of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). The results show that the cell viability, SOD activity, and MMP of the model group induced by H/R injury decreased, as compared with control group, but the necroptosis rate, LDH level, and ROS release increased significantly. Furthermore, mPTP of the model group cells opened, and TNF-α, IL-1β, and IL-6 levels were significantly higher. Molecular docking modeling showed that tilianin can bind to calmodulin-dependent protein kinase II (CaMKII), and Western blot results showed that compared with control group, the expression levels of p-CaMKII and phospho-mixed lineage kinase domain-like protein increased in the model group, and tilianin could decrease the expression level of these proteins. The above results indicate that tilianin can protect H9c2 cells by inhibiting the phosphorylation of CaMKⅡ at threonine 287, protecting mitochondrial function, and inhibiting the opening of mPTP to prevent necroptosis. This study has value for research on new methods to treat H/R injury.

Prevalence and influencing factors of sarcopenia in maintenance hemodialysis patients / 中华肾脏病杂志

Objective:To determine the prevalence of sarcopenia and explore related influencing factors of sarcopenia in maintenance hemodialysis (MHD) patients.Methods:MHD patients aged ≥18 years old and receiving therapies of ≥3 months from March 2019 to December 2019 in Blood Purification Centre of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively enrolled in this study. General data of the patients were collected. Grip strength was measured by the Jamar dynamometer and the chair stand was measured by a chair of standard height to assess skeletal muscle strength and appendicular skeletal muscle mass was measured by dual energy X-ray absorptiometry. Baseline data between MHD patients with and without myasthenia were compared. Logistic regression analysis method was used to analyze the influencing factors for sarcopenia in MHD patients.Results:A total of 125 MHD patients were enrolled, with 68 males (54.4%), age of (59.4±14.9) years and median dialysis age of 51.0(23.5, 101.0) months. Sarcopenia was diagnosed in 39 cases (31.2%). Compared with MHD patients without sarcopenia, age, tumor necrosis factor-α, von Willebrand factor (vWF) and proportion of using α ketones were higher, and serum carbondioxide combining power (CO 2CP), prealbumin, albumin and proportion of regular exercise were lower in MHD patients with sarcopenia (all P<0.05). Multivariable logistic regression analysis results showed that low CO 2CP ( OR=0.717, 95% CI 0.576-0.892, P=0.003), high vWF ( OR=1.037, 95% CI 1.016-1.058, P<0.001) and no regular exercise ( OR=0.309, 95% CI 0.118-0.810, P=0.017) were independent influencing factors of sarcopenia in MHD patients. Conclusions:The prevalence of sarcopenia in MHD patients is high. Low CO 2CP, high vWF and no regular exercise are independent influencing factors for sarcopenia in MHD patients.

Analysis of Influential Parameters on Tacrolimus Dosage and Concentration One Year after Lung Transplantation / 中国药学杂志

OBJECTIVE: To investigate the influence of patients' genetic and clinical parameters on tacrolimus dosage and concentration after lung transplantation. METHODS: A total of 50 patients who had received lung transplantation in our hospital from April 2017 to August 2018 were enrolled in this study. Information was collected 1 year after transplantation. Tacrolimus concentration was determined by chemiluminescent microparticle immunoassay (CMIA) and CYP3A5 genotype was detected by Sanger sequencing. Body weight adjusted dosage (D) and dosage adjusted concentration (C/D) were calculated. Influence of CYP3A5 genotype on D and C/D were analyzed. Multiple linear regression was performed to determine influential factors on tacrolimus dosage 1 year after lung transplantation. RESULTS: While maintaining tacrolimus concentration within therapeutic range, dosage requirement for CYP3A5*1/*1 and *1/*3 patients was higher than that of *3/*3 patients and C/D value was lower than that of *3/*3 patients (P<0.05). Multivariable linear regression results showed that CYP3A5 genotype, hemoglobin and age had significant influence on tacrolimus D, among which hemoglobin and age showed negative correlation (P<0.05). Prediction equation for tacrolimus D was obtained by multivariable linear regression. The correlation coefficient between predicted dose and actual dose was 0.824 (95% CI: 0.705-0.893). CONCLUSION: Tacrolimus dosage after lung transplantation is influenced by CYP3A5 genotype, hemoglobin and age. Using these factors for tacrolimus dosage prediction could possibly be instructive for individualized use of tacrolimus.

S100a4 promotes differentiation of neural stem cells through up-regulation of brain-derived neurotrophic factor / 中国组织工程研究

BACKGROUND: How to promote neural stem cells differentiate into neurons is a difficulty. S100A4 has been found to play a role in the nervous system repair by various pathways. OBJECTIVE: To investigate whether S100A4 affects the differentiation of neural stem cells into neurons through up-regulating the expression of brain-derived neurotrophic facto. METHODS: The neural stem cells from brain hippocampus and subependymal region of embryonic mice were cultured in vitro and passaged. The S100A4 expression vector and/or brain-derived neurotrophic factor + siRNA were transfected into neural stem cells by electroporation, and the cells were induced to differentiate into neurons at 48 hours after transfection. Three days later, the expression levels of brain-derived neurotrophic factor and Tuj1 in cells were detected by western blot assay. Proportion of Tuj1 positive neurons was tested by immunofluorescence. RESULTS AND CONCLUSION: Compared with the unrelated sequence plasmid group, the proportion of Tuj1 positive neurons and the expression levels of Tuj1 and brain-derived neurotrophic factor in the S100A4 transfection group were significantly increased (P < 0.01). Compared with the S100A4+siRNA unrelated sequence plasmid group, the proportion of Tuj1 positive neurons and the expression levels of Tuj1 and brain-derived neurotrophic factor in the co-transfection group were significantly decreased (P < 0.01). These results indicate that S100A4 overexpression can promote the differentiation of neural stem cells into neurons, which may be mediated by brain-derived neurotrophic factor.

Effect of acupoint stimulation on the quality of recovery in patients with radical thyroidectomy under the concept of enhanced recovery after surgery: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of acupoint stimulation on the quality of recovery in patients with radical thyroidectomy under the concept of enhanced recovery after surgery (ERAS).@*METHODS@#A total of 62 patients with radical thyroidectomy were randomized into an observation group and a control group, 31 cases in each one. In both of the two groups, general anesthesia with tracheal intubation was applied, the same anesthesia induction and maintenance medication were given. In the observation group, auricular point pressing with magnetic beads was adopted at bilateral shenmen (TF) and transcutaneous electrical acupoint stimulation (dilatational wave, 2 Hz/100 Hz in frequency, 6 to 12 mA) was performed at bilateral Hegu (LI 4) and Neiguan (PC 6) from 30 min before anesthesia induction to the end of the anesthesia. In the control group, medical adhesive plaster was pasted at bilateral shenmen (TF) and the electrodes were plastered at bilateral Hegu (LI 4) and Neiguan (PC 6) with no corresponding stimulation. In both of the two groups, visual analogue scale for anxiety (VAS-A) score was observed to evaluate the anxiety severity before anesthesia induction; the total intraoperative dosages of sufentanil, remifentanil and propofol were recorded; the numerical rating scale (NRS) score was used to assess the pain severity of instant time (T0) and 30 min (T1) of entering post-anesthesia recovery room (PACU), motor and static mode at 2 h (T2), 6 h (T3), 12 h (T4), 24 h (T5) after surgery; time of first anal exhaust, time of getting out of bed after surgery, total hospitalization time and the incidences of postoperative nausea and vomiting were observed; the quality of recovery was assessed by the 40-item quality of recovery score (QoR-40).@*RESULTS@#The VAS-A score and the total intraoperative dosage of remifentanil in the observation group were reduced compared with the control group (0.05). The time of first anal exhaust and getting out of bed after surgery in the observation group were advanced than those in the control group (0.05). Compared with the control group, the QoR-40 score was increased in the observation group (<0.05).@*CONCLUSION@#Acupoint stimulation can improve the preoperative anxiety in patients with radical thyroidectomy, reduce the intraoperative anesthetic dosage and postoperative pain, advance the time of anal exhaust and getting out of bed, improve the quality of postoperative recovery and enhance the recovery process.

Protective effect and mechanism of total flavonoids of Dracocephalum moldevica on doxorubicin myocardial toxicity / 中草药

Objective: To explore the protective effect and mechanism of total flavonoids of Dracocephalum moldevica (TFDM) on doxorubicin-induced cardiotoxicity. Methods: H9c2 cells were induced with 1 μmol/L doxorubicin for 24 h to establish a cardiotoxicity model. H9c2 cells were randomly divided into control group, model group, and drug intervention group (four subgroups of 5, 25, 50, and 100 μg/mL). After the intervention of TFDM, the doxorubicin cardiotoxicity model was established in the other groups except the control group. The cell counting Kit-8 method was used to determine the viability of H9c2 cells induced by doxorubicin injury after the intervention of TFDM. The effects of lactate dehydrogenase release, intracellular superoxide dismutase and malondialdehyde in each group were determined by kit method. The apoptosis rate of each group was detected by flow cytometry using Annexin-V FITC/PI double staining method. Reactive oxygen species (ROS) and mitochondrial membrane potential in each group were detected by DCFH-DA and JC-1 probes. The expressions of p38MAPK, ERK1/2, and PI3K/Akt pathway-related proteins were detected by Western blotting. Results: Compared with the control group, the cell viability of the model group induced by doxorubicin was decreased, the release of lactate dehydrogenase and the content of malondialdehyde were increased, the activity of superoxide dismutase was decreased, the apoptosis rate was increased, the release of reactive oxygen species was increased significantly, and the mitochondrial membrane potential was decreased significantly. However, TFDM increased H9c2 cell viability, decreased LDH and MDA levels, increased SOD activity, decreased apoptosis rate, significantly decreased ROS release, and significantly increased MMP in a dose-dependent manner. The difference was statistically significant. The results of Western blot showed that the expression levels of p-PI3K, p-Akt, p-ERK1/2, and Bcl-2 were decreased, and the expression levels of p-p38MAPK, Bax and Caspase-3 were significantly increased compared with the control group. However, in the TFDM-treated group, the expression of p-PI3K, p-Akt, p-ERK1/2, and Bcl-2 protein was increased, and the protein expression of p-p38MAPK, Bax, and Caspase-3 protein was decreased. Conclusion: TFDM can protect cardiomyocytes, and its protective mechanism may be related to the resistance to oxidative stress, protection of cardiomyocyte mitochondria, and regulating MAPK enzyme family proteins, and PI3K/Akt signaling pathway and subsequent release of apoptotic cytokines to inhibit apoptosis.

Progress in immunotherapy targeting PD-1/PD-L1 for lung cancer / 中国实用内科杂志

Lung cancer is the leading cause of cancer-related mortality with high malignancy. In recent years, a major breakthrough has been made in immunotherapy targeting PD-1/PD-L1 for lung cancer, which altered the traditional therapeutic pattern of lung cancer and heralded the dawn of the new immune era. This paper reviewed the application of immune checkpoint blockers in the subtypes of lung cancer, immune-related adverse events, the selection of potential biomarkers, and the exploration of resistance mechanisms.

Association analysis of PPP1R3A gene polymorphism with schizophrenia in Uygur Chinese population / 中国神经精神疾病杂志

Objective To explore the correlation between exon region polymorphism of PPP1R3A gene and schizophrenia in Uygur Chinese population. Methods PPP1R3A gene exon region DNA amplification was performed using multiple PCR targeted capture next-generation sequencing method in 528 patients with schizophrenia and 576 healthy controls of Uyghur descent, Illumina HiSeq X Ten was used for sequencing, the symptoms of schizophrenia were assessed by positive and negative symptoms scale (PANSS). Results The allelic and genotypic distributions in rs1800000 of PPP1R3A gene between patients with schizophrenia and healthy controls had significant difference (P＜0.05), rs1799999 in genotype frequency between the female case and control groups showed significant difference (P＜0.05). Furthermore, the allelic distributions of rs8192686 between male cases and controls had significant difference (P＜0.05). Conclusion PPP1R3A gene rs1800000 may be associated with the development of schizophrenia in Uygur Chinese population; rs1799999 may be a risk factor for susceptibility of female Uygur Chinese schizophrenia; The C allele at rs8192686 may be associated with male Uygur Chinese schizophrenia.

A research on predictive value of plane QRS-T angle for postoperative malignant ventricular arrhythmia of patients with AMI undergoing PCI and the correlation analysis between the predictive value and prognostic effect / 中国医学装备

Objective: To analyze predictive value of plane QRS-T angle for postoperative malignant ventricular arrhythmia (MVA) of patients with acute myocardial infarction (AMI) who underwent PCI and the correlation between the predictive value and prognostic effect. Methods: The clinical data of 100 patients with AMI who underwent the treatment of percutaneous coronary intervention(PCI) were researched by using retrospective analysis. All of patients were divided into observation group (24 cases) and control group (76 cases) according to the angle of plane QRS-T after PCI. The plane QRS-T angle of observation group was more than 90°, and it was less than or equal to 90° in control group. The occurrence of MVA and clinical outcome of MVA between the two group were compared. Results: The age of observation group was significantly higher than that of control group (t=3.516, P<0.05). The interval of QTc of observation group was significantly higher than that of control group (t=2.131, P<0.05). And the percentage of left ventricular ejection fraction (LVEF) less than 45%, the occurrence rate of high blood pressure and the occurrence rate of MVA of observation group were significantly higher than those of control group (x2=3.922, x2=3.950, x2=5.942, P<0.05), respectively. The results of multi-factor Logistic regression analysis indicated that the angle of plane QRS-T of patients with AMI after PCI above 90° was the independent risk factor of MVA after PCI (OR=9.640, P<0.05). Conclusion: After the PCI of patients with AMI, the QRS-T angle> 90 ° was an independent risk factor of MVA.

The analysis of low cost medicine's accessibility in China: Based on the empirical study from 24 provinces and cities / 中国卫生政策研究

Objective:To analyze the satiation of low cost medicine at present and provide suggestions for im-proving the low cost medicine policy since it has been conducted. Methods: The article uses the statistics from 24 provinces and cities to analyse the accessibility of low cost medicine with the angles of general condition,procurability and affordability. Results:The accessibility of low cost medicine is high through its policy knowledge is low. For pro-curability, there are only part of low cost medicine lacking in several areas momently; for affordability, the price of low cost medicine is affordable even through its price has been raised after the performance of policy. The reasons for shortage includes low price,check price transaction,lack of raw and processed material and small quantity demand of some medicine,etc. Conclusions:We suggest that government should improve the knowledge of this policy in hospi-tals and encourage low cost medicine in clinical applications. It also should lead companies to set the appropriate price and refine the purchasing system which will avoid the too high or too low price and help to ensure the amount and standard of companies that be selected in purchasing online. At the same time, government is supposed to strengthen the supervision on supply chain of low cost medicine and establish the communication mechanism for sup-ply system in order to guarantee the regulated supply of low cost medicine.

Correlation of four gene polymorphic loci with athlete endurance phenotype / 中国组织工程研究

BACKGROUND: Increasing evidence shows that at least 155 genetic polymorphisms are associated with aerobic performance and elite endurance athlete status. OBJECTIVE: To study the association of α-actin 3 (ACTN3) gene, nuclear respiratory factor 2 (NRF2), β2 adrenergic receptor (ADRB2) gene and peroxisome proliferative activated receptor gamma coactivator 1 alpha (PPARGC1A) polymorphic loci with aerobic performance of rowing athletes and their interaction effect, thereby providing basis for understanding the mechanism of genetic polymorphisms acting on endurance athlete status. METHODS: A case-control experiment was designed to analyze the distribution characteristics of four gene polymorphism loci in 15 excellent rowing athletes and 50 common college freshmen. The association of four polymorphic loci with the aerobic performance-related indexes was analyzed using total genotype scores. RESULTS AND CONCLUSION: The preponderant polymorphism locus distributions of ACTN3, PPARGC1A and NRF2 in the athletes group were higher than those in the control group, and the NRF2 gene loci showed significant difference between two groups. In the athletes group, the mean values of VO2 maxwas significantly different among three genotypes. That is to say, these three genetic polymorphisms may be the biomarkers to predict the elite endurance athlete status, but the mechanism needs to be studied in depth.