OBJECTIVE To establish the quality standard of Triadica cochinchinensis and to perform the acute toxicity study. METHODS Appearance properties, powder microscopic identification, and thin-layer chromatography(TLC) identification were researched. The specific chromatogram was established by HPLC. The content of cadmium(Cd), lead(Pb), arsenic(As), copper(Cu), and mercury(Hg) was determined by inductively coupled plasma-mass spectrometry(ICP-MS). Acute toxicity was studied by maximum dose. RESULTS The outer skin of herbs was dark brown, and the inner surface was light yellow brown and fibrous. Besides, crystal sheath fiber was common, and calcium oxalate clusters arranges in rows. In the TLC diagram of the test product, the fluorescent spots of the same color were displayed at the corresponding position of the control product(scopoletin, isofraxidin). Five common peaks were calibrated in the characteristic map and the three characteristic peaks(scopoletin, isofraxidin, dimethylfraxetin) were recognized. The content of the measured heavy metal elements was lower than the national limit standard. The linear correlation coefficient was R2 > 0.999. The precision, stability, repetitive RSD were < 10%. The average recovery rate of the added sample was 80%−120%, and the RSD was < 10%. The maximum dose of the acute toxicity test was 184.09 g·kg−1. The 14 d internal body mass, food intake, organ-body ratios, the serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, blood urea nitrogen, and creatinine were not significantly different by comparing with the normal controls. Therefore, no significant toxicity was observed. CONCLUSION The established standard can provide a reference for evaluating the quality of Triadica cochinchinensis. The heavy metal content of ten batches of medicinal materials is within the safe range. Acute toxicity test show that there is no obvious significant adverse teactions after oral administration, and the safe dose range is large, which can provide a reference for the subsequent development and utilization.

Heat stroke(HS)is a serious life-threatening disease caused by heat injury and characterized by a core body temperature>40℃with central nervous system dysfunction and multi-organ failure.The main pathophysiological manifestations of HS are the thermal acute phase response and thermoregulatory imbalance.Proteins are particularly sensitive to heat,and the thermal environment can cause massive protein denaturation,resulting in the deposition of unfolded and misfolded proteins in the cytoplasm,causing cellular dysfunction and even death.The unfolded protein response(UPR),mainly divided into the endoplasmic reticulum UPR and the mitochondrial UPR,is an important physiological process that helps proteins to fold correctly or degrade irretrievably denatured proteins.This paper summarizes the regulatory mechanisms of UPR,the relationship between UPR and severe diseases,as well as the relationship between HS and UPR to provide new ideas for the treatment of HS.

In order to assist in the standardization and maturity evaluation of national hospital information interconnection, and further standardize the application and management of hospital medical record data, a hospital carried out the practice of design of structured medical records and the corresponding quality management from April 2021. Based on the six sigma quality management method, the hospital had developed universal templates for electronic medical records and a list of candidate electronic medical record templates. The problems faced by medical record data had been analyzed, and improvement strategies had been proposed from three levels: template design, software functionality and management services. The clinical departments were guided to design and develop various structured electronic medical record templates for specialties and specialized diseases, and established a medical record template design and quality management method. The hospital had ultimately designed a total of 614 structured electronic medical record templates that met the actual needs of the hospital. This practice enhanced the scalability of structured templates and quality of the data, and achieved localization and specialization of medical record templates while meeting the requirements of information interconnection and sharing, providing reference for promoting the interconnection and sharing of electronic medical records of hospitals in China.

BACKGROUND: Recent cardiovascular outcome trials (CVOTs) changed the therapeutic strategy of guidelines for type 2 diabetes. We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials. METHODS: This electronic medical record (EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1, 2011, to June 30, 2019. We identified patients meeting the inclusion criteria of a pragmatic randomized trial (EMPA-REG OUTCOME) based on EMRs and compared their baseline characteristics with those of the trial participants. The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation. RESULTS: We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389 (17.4%) inpatients and 2646 (7.2%) outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial. Compared with the trial population, the real-world inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age, blood pressure, and lipid profiles but comprised of fewer males, metformin users, anti-hypertensive drug users, and aspirin users, and had a lower body mass index. The group of outpatients meeting the eligibility criteria had fewer males, similar age, fewer metformin users, fewer insulin users, fewer anti-hypertensive drug users, and fewer aspirin users compared with the trial population. CONCLUSIONS The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center. Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.
Benzhydryl Compounds ; Canagliflozin ; Cardiovascular Diseases ; China ; Diabetes Mellitus, Type 2/drug therapy* ; Glucosides ; Humans ; Male ; Sodium-Glucose Transporter 2 Inhibitors ; Tertiary Care Centers

OBJECTIVE: To study the value of fast spin-echo diffusion weighted imaging (TSE-DWI) apparent diffusion coefficient (ADC) in children aged 2-12 years with intellectual disability (ID)/global developmental delay (GDD) who have normal conventional brain MRI findings. METHODS: A total of 578 children with normal conventional brain MRI findings who met the diagnostic criteria for ID/GDD and 375 normal children were enrolled. Their imaging and clinical data were collected. All children underwent scanning with brain TSE-DWI sequence and routine sequence. ADC values of each brain region were compared between normal children with different ages, as well as between children with different degrees of ID/GDD in each age group. The influence of Adaptive Behavior Assessment System-II (ABAS-II) score on ADC values of each brain region was analyzed. RESULTS: For the normal children, the ADC values of the frontal and temporal white matter, the corpus callosum, the inner capsule, the centrum semiovale, the cerebellar dentate nucleus, the optic radiation, the thalamus, the lenticular nucleus, and the caudate nucleus gradually decreased with age (P<0.05). ADC values of the deep white matter, the shallow white matter, the deep gray matter nuclei, and the shallow gray matter increased with the increase in the degree of ID/GDD in the ID/GDD children aged 4-6 years (P<0.05). In the children with ID/GDD, the ADC values of the deep white matter, the shallow white matter, and the deep gray matter nuclei decreased with age (P<0.05). The ADC values of the children with ID/GDD decreased with the increase in ABAS-II score (P<0.05). CONCLUSIONS ADC can reflect the subtle structural changes of brain regions in children with ID/GDD who have normal conventional brain MRI findings. It may be associated with social adaptation. It can provide an objective basis for the quantitative diagnosis of ID/GDD in children.
Brain ; Child ; Child, Preschool ; Diffusion Magnetic Resonance Imaging ; Humans ; Intellectual Disability ; diagnostic imaging ; Magnetic Resonance Imaging ; White Matter

Haploinsuffieiency of the runt-related transcription factor 2 (Runx2) gene is widely known to be responsible for cleidocranial dysplasia (CCD).To date,more than 190 mutations in Runx2 gene have been reported to be related to CCD.In this study,a novel mutation of Runx2 gene was observed in a female with CCD.Genomic DNA was extracted from peripheral venous blood of the proband and eleven members of her family.Genetic testing on these twelve people identified a novel missense mutation (c.895T＞C,Y299H) in exon 5 of the RUNX2 gene in the proband.This mutation results in an amino acid change at codon 895 (P.Tyr 299 His.) from a tryptophan codon (TAT) to a histidine codon (CAT).Our finding may further extend the known mutation spectrum of the RUNX2 gene,and facilitate prenatal genetic diagnosis of CCD in the future.

Objective To investigate the effects of anti?PD?L1 monoclonal antibody and EGFR?TKI on expression of soluble PD?L1 and function of T lymphocytes in EGFR?mutated lung cancer cells. Methods Flow cytometry was used to analyze the expression of membrane PD?LI. ELISA was performed to detect the level of sPD?L1 in the supernatant of cultured EGFR?mutated and wild type lung cancer cells before and after erlotinib treatment. After treated with anti?PD?L1 monoclonal antibody alone and in combination with erlotinib, the proliferation of T lymphocytes in co?culture system was measured using Cell Counting Kit?8 ( CCK?8) assay. The expression levels of PD?LI and IFN?γin tumor cells and T lymphocytes treated with erlotinib in co?culture system were analyzed by flow cytometry and ELISA, respectively. Results PD?L1 was highly expressed in EGFR?mutated lung cancer PC9 cells (78.7±3.1)% and HCC827 cells (82. 7±2.6)%.After treated with erlotinib, the expression rates of membrane PD?L1 in PC9 and HCC827 cells were down?regulated (64.7%±3.1% and 73.0%±2.6%, respectively),significantly lower than that in the two cell lines without erlotinib treatment ( P<0.05) , and the expression levels of sPD?L1 in the supernatant of PC9 and HCC827 cells were also down?regulated ( 0. 680 ± 0. 120) ng/ml and ( 0. 903 ± 0. 047) ng/ml, respectively, significantly lower than that in the two cell lines without erlotinib treatment ( P<0. 01 ) . However, no significant changes of membrane PD?L1 and sPD?L1 expression were found in EGFR wild type lung cancer cells ( H1299 and A549) before and after erlotinib treatment. In the co?culture system composed of T cells and EGFR?mutated lung cancer cells, treatment with erlotinib alone promoted the proliferation of T lymphocytes (P<0.05), and combined treatment of anti?PD?L1 monoclonal antibody with erlotinib had a stronger effect ( P<0.05) . In the co?culture system composed of T cells and EGFR wild type cell lines, the proliferation of T cells was not changed after using erlotinib alone or combination of erlotinib and anti?PD?L1 monoclonal antibody ( P>0.05) . Before and after treatment with erlotinib, the secretion levels of IFN?γwere (856.0± 70. 3) pg/ml and ( 1 697. 3 ± 161. 0) pg/ml, respectively, showing a significant difference ( P<0.001). The expression rates of membrane PD?L1 were (76.2±0.5)% and (50.9±0.9)%, respectively, also showing a significant difference ( P<0.001) . However, no significant changes in the expression of IFN?γ and membrane PD?L1 were found in the co?culture system composed of T cells and A549 cells. Conclusions Anti?PD?L1 monoclonal antibody combined with EGFR?TKI can effectively promote the proliferation and secretion function of T lymphocytes in the microenvironment of EGFR?mutated lung cancer cells.

Objective To investigate the effects of anti?PD?L1 monoclonal antibody and EGFR?TKI on expression of soluble PD?L1 and function of T lymphocytes in EGFR?mutated lung cancer cells. Methods Flow cytometry was used to analyze the expression of membrane PD?LI. ELISA was performed to detect the level of sPD?L1 in the supernatant of cultured EGFR?mutated and wild type lung cancer cells before and after erlotinib treatment. After treated with anti?PD?L1 monoclonal antibody alone and in combination with erlotinib, the proliferation of T lymphocytes in co?culture system was measured using Cell Counting Kit?8 ( CCK?8) assay. The expression levels of PD?LI and IFN?γin tumor cells and T lymphocytes treated with erlotinib in co?culture system were analyzed by flow cytometry and ELISA, respectively. Results PD?L1 was highly expressed in EGFR?mutated lung cancer PC9 cells (78.7±3.1)% and HCC827 cells (82. 7±2.6)%.After treated with erlotinib, the expression rates of membrane PD?L1 in PC9 and HCC827 cells were down?regulated (64.7%±3.1% and 73.0%±2.6%, respectively),significantly lower than that in the two cell lines without erlotinib treatment ( P<0.05) , and the expression levels of sPD?L1 in the supernatant of PC9 and HCC827 cells were also down?regulated ( 0. 680 ± 0. 120) ng/ml and ( 0. 903 ± 0. 047) ng/ml, respectively, significantly lower than that in the two cell lines without erlotinib treatment ( P<0. 01 ) . However, no significant changes of membrane PD?L1 and sPD?L1 expression were found in EGFR wild type lung cancer cells ( H1299 and A549) before and after erlotinib treatment. In the co?culture system composed of T cells and EGFR?mutated lung cancer cells, treatment with erlotinib alone promoted the proliferation of T lymphocytes (P<0.05), and combined treatment of anti?PD?L1 monoclonal antibody with erlotinib had a stronger effect ( P<0.05) . In the co?culture system composed of T cells and EGFR wild type cell lines, the proliferation of T cells was not changed after using erlotinib alone or combination of erlotinib and anti?PD?L1 monoclonal antibody ( P>0.05) . Before and after treatment with erlotinib, the secretion levels of IFN?γwere (856.0± 70. 3) pg/ml and ( 1 697. 3 ± 161. 0) pg/ml, respectively, showing a significant difference ( P<0.001). The expression rates of membrane PD?L1 were (76.2±0.5)% and (50.9±0.9)%, respectively, also showing a significant difference ( P<0.001) . However, no significant changes in the expression of IFN?γ and membrane PD?L1 were found in the co?culture system composed of T cells and A549 cells. Conclusions Anti?PD?L1 monoclonal antibody combined with EGFR?TKI can effectively promote the proliferation and secretion function of T lymphocytes in the microenvironment of EGFR?mutated lung cancer cells.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

BACKGROUNDChromosome 13q14 deletion (del13q14), chromosome 1q21 gain (amp1q21) and chromosome 17p13 deletion (del17p13) are the most frequent chromosomal aberrations in multiple myeloma (MM). They play an important role in prognosis. The aim of this study was to investigate the clinical significance of the chromosomal changes in Chinese MM patients.

METHODSInterphase fluorescence in situ hybridization (FISH) on bone marrow (BM) cells was performed in 72 enrolled MM patients. Relationships between chromosomal abnormalities and clinical features, response to therapies and prognosis were analyzed.

RESULTSAs a result of interphase FISH, 77.8% (56/72) patients had chromosome changes. The incidences of each probe were RB1 51.4% (37/72), D13S319 47.2% (34/72), 1q21 45.8% (33/72) and p53 22.2% (12/72). Osteolytic lesion, BM plasma cells index, serum calcium and serum M component were significantly correlated to del13q14. BM plasma cells and hemoglobin were correlated to amp1q21. Serum lactate dehydrogenase (LDH) was correlated with del17p13. Patients with del13q14 treated with bortezomib had a notably higher overall response rate than the patients treated with traditional chemotherapies (93% vs. 65%, P = 0.048). Patients carrying amp1q21 or/and del17p13 did not achieve satisfactory response to bortezomib. The median progression-free survival (PFS) for patients with amp1q21 was 5 months and patients without amp1q21 got 9-month PFS (P = 0.001). The median PFS for patients with del13q14 was 5 months (vs. 8 months, P = 0.026). The median PFS for patients with del17p13 was 3 months (vs. 8 months, P = 0.002). Patients with β(2)-microglobulin > 5.5 mg/L also had a worse outcome, whose median PFS was 5 months (vs. 8 months, P = 0.016).

CONCLUSIONSThe prevalence of chromosomal abnormalities of MM patients was similar in Chinese and Caucasian people. Genetic changes were associated with patients' responses to therapies and prognosis.

Adult ; Aged ; Asian Continental Ancestry Group ; Chromosome Aberrations ; Chromosome Deletion ; Humans ; In Situ Hybridization, Fluorescence ; Interphase ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; genetics ; Prognosis