The predictive value of PPV and SVV after tidal volume challengeon volumetric responsiveness in patients with ARDS / 重庆医学

Objective To explore the predictive value of pulse pressure variation(PPV),stroke volume variation(SVV)and their changing values after tidal volume increase from 6 mL/kg to 8 mL/kg predicted body weight(PBW)on the volumetric responsiveness in the patients with acute respiratory distress syndrome(ARDS).Methods A prospective study was conducted.Twenty-three ARDS patients with acute circulatory failure treated in the intensive care unit(ICU)of this hospital from January 2021 to December 2022 were se-lected.The indicators such as PPV,SVV and cardiac index were recorded at the tidal volume of 6 mL/kg PBW,1 min after tidal volume challenge(tidal volume instantly increased to 8 mL/kg PBW),the tidal volume re-reduced to 6 mL/kg PBW,and after fluid bolus(FB),respectively.The cardiac index increase(ΔCI)≥15％served as the volumetric responsiveness positive when the tidal volume was re-reduced to 6 mL/kg PBW and after giving FB.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of PPV,SVV and their changing values for the volumetric responsiveness after the tidal volume increase from 6 mL/kg to 8 mL/kg PBW.Results A total of 42 measurements were performed in 23 patients.Among them,24 set of measurements were volumetric responsiveness positive(group R),and 18 set of measurements were volumetric responsiveness negative(group NR).The absolute values(ΔPPV6-8,ΔSVV6-8)and percentage(％ΔPPV6-8,％ΔSVV6-8)of PPV and SVV in tidal volume increase from 6 mL/kg to 8 mL/kg PBW had statisti-cal differences between the two groups(P＜0.05).ΔPPV6-8 and ΔSVV6-8 could predict the volumetric respon-siveness in the patients with ARDS.The area under the ROC curve(AUC)and its 95％CI were 0.92(0.84-1.00)and 0.90(0.81-0.99),and the optimal cut off values were 2.5％and 3.5％,respectively.When the tid-al volume was 6 mL/kg PBW,the PPV,SVV and central venous pressure(CVP)could not effectively predict the volumetric responsiveness in the patients with ARDS.Conclusion The efficiency of PPV or SVV changing values after tidal volume challenge for predicting the volumetric responsiveness of ARDS patients during low tidal volume ventilation is superior to PPV and SVV.

Conversion of stromal vascular fraction in the microenvironment of radiation-induced skin injuries and its clinical implications / 中华放射医学与防护杂志

Objective:To investigate the conversion of stromal vascular fraction (SVF) in the microenvironment of radiation-induced skin injuries to provide guidance for clinical applications.Methods:Based on a random number table, C57BL/6N mice were categorized into four groups: the blank control, negative control, acute injury, and chronic injury groups, with each group containing 25 mice. The backs of mice in the blank control, acute injury, and chronic injury groups were exposed to 15 Gy X-ray irradiation. Then, the mice in the negative control, acute injury, and chronic injury groups were injected subcutaneously with the SVF derived from B6/G-R mice. The survival of these mice was observed 1, 3, 7, 14, and 21 d after the injection through fluorescence tracing and in vivo imaging. Accordingly, the clinical SVF injection regimens were optimized based on the experimental result of mice. Finally, local SVF injection was performed on different frequencies for patients in different wound conditions, with the efficacy being observed. Results:The fluorescence of SVF was observed from the tissue slices of the acute injury, chronic injury, and negative control groups 14 d post-injection. The result showed that the fluorescence intensity of SVF 1, 3, and 7 d post-injection was in the order of the negative control group > the acute injury group > the chronic injury group. The acute injury group ranked at the top and the chronic injury group remained at the bottom 14 d after the injection. The fluorescence of SVF in each group was barely detected 21 d after the injection. Compared to the negative control group, the acute injury group exhibited statistical differences only 14 d post-injection ( t = 4.11, P < 0.05), while the chronic injury group displayed statistical differences 1, 3, 7, and 14 d after the injection ( t = 3.88-5.74, P < 0.05). Furthermore, the acute injury group exhibited significantly higher fluorescence intensity of SVF than the chronic injury group ( t = 4.73-8.38, P < 0.05). The half-life of SVF for the negative control, acute injury, and chronic injury groups was 6.336, 6.014, and 2.163 d, respectively. As indicated by the application of SVF transplantation based on traditional surgical protocols in the clinical trial, SVF can significantly promote wound repair, with earlier SVF transplantation being more beneficial for wound healing. Conclusions:The conversion of SVF differs in the microenvironments of acute and chronic radiation-induced skin injuries. This can serve as an essential guide for the administration timing and injection frequency of SVF in clinical applications.

Study on the toxic mechanism of Mahuang xixin fuzi decoction based on fecal metabolomics / 中国药房

OBJECTIVE To study the toxic mechanism of Mahuang xixin fuzi decoction （MXF） on normal mice. METHODS Totally 48 SPF grade BABL/C mice were randomly divided into blank group， MXF low-dose， medium-dose and high-dose groups， with 12 mice in each group. MXF low-dose， medium-dose and high-dose groups were given drug intragastrically at the dose of 11.262， 33.786， 45.050 g/kg， respectively. Blank group was administered with equal volume of normal saline， once a day， for consecutive 7 d. The body weight， anal temperature and survival rate were recorded， organ index and serum biochemical factors were detected. After the last administration， fecal samples of mice were collected and detected by UHPLC-QE/MS. RESULTS Compared with blank group， the body weight was decreased significantly from the 3rd to the 5th day after administration in MXF medium-dose group， and from the 2nd to the 7th day after administration in MXF high-dose group significantly （P＜0.05）. There was no significant difference in anal temperature among the treatment groups； the average survival rates of MXF medium-dose and high-dose groups were 58.33% and 50.00%， respectively. Compared with blank group， there were significant difference in the indexes of spleen， lung， thymus， adrenal gland and creatine kinase in MXF low-dose， medium-dose and high-dose groups， the testis index in MXF low-dose and high-dose groups， the creatine kinase isoenzyme/creatine kinase ratio in MXF low-dose group， the α-hydroxybutyrate dehydrogenase， lactate dehydrogenase and alkaline phosphatase in MXF medium-dose group， the urine and cystatin C in MXF medium-dose and high-dose groups （P＜0.05）. The fecal metabonomic analysis showed that 19 biomarkers such as phenylpyruvate， L-tyrosine， phosphatidylcholine， glycerol 3-phosphate in MXF low-dose， medium-dose and high-dose groups were significantly different from those in the blank group. CONCLUSIONS When MXF reaches a certain dose， it will have adverse effects on the body weight， multiple organs and serum biochemical indicators of mice， thus showing a certain toxic effect. Its mechanism may be related to disrupting the intestinal flora metabolism， causing inflammatory reaction and immune disorders.

Research progress and clinical application of the visual functioning index / 国际眼科杂志(Guoji Yanke Zazhi)

Cataract surgery has moved from the era of anti-blindness surgery to the era of refractive surgery, and vision-related quality of life has become an important prognostic indicator for cataract surgery. Since indicators like visual acuity are difficult to describe the visual quality of patients in a panoramic view, the evaluation of visual function based on subjective experience has received attention in clinical and scientific research. The visual functioning index(VF-14)is the first scale applied to assess the visual function in cataract surgery, and is widely used internationally so far. This review presented the research history of VF-14, scrutinized its clinical applicability, and summarized the research and application of VF-14 in the assessment of visual function, evaluation of surgical efficacy, and postoperative follow-up from three groups of people with cataract, refractive discomforts, and other common ophthalmic diseases, aiming to provide a reference for the clinical application of the VF-14.

Simplified Study of Constitution in Chinese Medicine Questionnaire Based on Genetic Algorithm and KNN Method / 世界科学技术-中医药现代化

Objective Aiming at the problems of many items and long time to fill in the Constitution in Chinese Medicine Questionnaire(CCMQ)when evaluating individual constitution,the research uses artificial intelligence technology to select attributes,and to help construct a short version of the CCMQ.Methods Analyzing the constitution data provided by the Physical Examination Department of Jiangsu Province Hospital of Traditional Chinese Medicine,there are specific target variables as the classification of constitution types.Feature selection of genetic algorithm,cross-validation and KNN classification algorithm are used as filters to select problems,and the effect is evaluated by problem subset size,KNN classification accuracy and filling time.Results The method selected a short version of the CCMQ with 31 problems,and the average classification accuracy in the model was 86.16%,and the time was improved by 47.7%.Conclusion The algorithm can effectively find a better problem subset,achieve dimensionality reduction and have certain accuracy,thus helping to simplify the CCMQ.

Application value of bedside ultrasound assessment of diaphragmatic dysfunction in sepsis patients / 中华急诊医学杂志

Objective:To evaluate the risk factors for diaphragmatic dysfunction of patients with sepsis and septic shock, and the application value of bedside ultrasound.Methods:Patients with sepsis and septic shock in the Intensive Care Unit (ICU), General Hospital of Ningxia Medical University from January 2020 to May 2021 were prospectively recruited as the research subjects, general postoperative patients and healthy volunteers were admitted as postoperative control and normal control groups. General clinical data were collected, patients with sepsis and septic shock were dynamically observed high sensitive c-reactive protein (hs-CRP), interleukin-6 (IL-6), serum albumin, transferrin, prealbumin levels, blood lactate, Pcv-aCO 2, ScvO 2, etc.; and indirect calorimetry was used to measure the resting energy level of the patient to calculate the missing energy value. Bedside ultrasound was used to dynamically evaluate the changes of diaphragm excursion (DE),inspiratory diaphragm thickness, and expiratory diaphragm thickness, to calculate relevant parameters. DE<10 mm or diaphragmatic thickness fraction (DTF) < 20% was diagnosed as diaphragmatic dysfunction. Results:(1) On day 1 in the ICU, the DE of the septic shock group, sepsis group and postoperative control group were significantly lower than that in the normal control group [10.3 (9.0, 13.6) mm, 12.3 (9.1, 15.0) mm, 12.9 (10.5, 15.7) mm vs. 22.0 (16.0, 24.6) mm, all P<0.05], and the incidence of DTF<20% was significantly higher than in the normal control group (32.7%, 41.9%, 33.3% vs. 0 %, all P<0.05), and the incidence of DE<10 mm in the septic shock group and sepsis group was significantly higher than that of postoperative control group and normal control group (36.7%, 35.5% vs. 10.0%, 0%, respectively, all P<0.05). On day 7, the DE in the septic shock group was significantly lower than that in the sepsis group [10.5 (6.8, 13.5) mm vs. 14.4 (10.6, 18.6) mm, P<0.05].(2) Correlation analysis of each index: The DE of patients with sepsis and septic shock on day 1, 3, and 7 was negatively correlated with the hs-CRP ( r=-0.253, -0.436, -0.455, all P<0.05); On day 3, DE was also negatively correlated with IL-6 ( r=-0.338, P=0.009); and DTF was negatively correlated with hs-CRP ( r=-0.375, P=0.004). On day 1, there was a positive correlation between DTF and serum transferrin levels in patients with sepsis and septic shock ( r=0.221, P=0.049). On day 3 and 7, the DE was positively correlated with serum prealbumin levels ( r=0.318, 0.408, both P<0.05). Conclusions:Patients with sepsis and septic shock have developed diaphragmatic dysfunction on day 1 in the ICU, which is mainly manifested as decreased in diaphragm mobility and diaphragmatic thickness fraction, and is related to inflammation and high protein catabolism.

Prevalence of osteoporosis and its influence factors in monitored population in Chongqing / 公共卫生与预防医学

Objective To understand the prevalence of osteoporosis and its influence factors in residents of Chongqing, and to provide the reference for osteoporosis prevention and treatment. Methods The data were from “An epidemiological survey of osteoporosis in Chongqing in 2018”, and the multi-stage stratified cluster random sampling method was used to select 1885 subjects (≥20 years old) from 32 villages/neighborhood committee in 4 areas (countries) of Chongqing. The investigation was performed by questionnaire (sociodemographic factors, lifestyle factors, history of orthopedics) and the bone mineral density was measured by QDR 4 500A dual energy X-ray absorptiometry. The chi-square test and multi factor multi-variant logistic regression analysis were utilized to analyze the data, the used software was SPSS 25.0. Results The morbidities of osteoporosis and osteopenia in residents (>20 years old) of Chongqing in China were 12.99% and 48.70%, respectively. The osteoporosis morbidity (19.08%) in females was significantly higher than that (4.42%) in males, and increased with age. The multi-variant logistic regression indicated that women (OR=6.10, 95% CI:4.08-9.14), the past medical history of fracture (OR=1.79, 95%CI:1.18-2.73) and age (OR=16.80, 95% CI:9.19-30.77) were risk factors for osteoporosis; milk intake (OR=0.65, 95%CI:0.47-0.89), overweight (OR=0.51, 95%CI:0.36-0.93)and obesity (OR=0.30, 95%CI:0.19-0.47), as compared with ≤primary school group, junior high school group (OR=0.57, 95%CI:0.39-0.82);≥high school group (0.40, 95%CI:0.26-0.61) were considered to be protective factors for osteoporosis. Conclusion The prevalence of osteoporosis among residents with age above 50 years old of Chongqing was very high. Health education and behavior intervention should be focused on the elderly or female residents to promote the formulation of healthy lifestyle.

Study on mechanism of curcumol against liver fibrosis based on autophagy and apoptosis of hepatic stellate cells / 中国中药杂志

The present study clarified the molecular mechanism of curcumol against liver fibrosis based on its effects on the autopha-gy and apoptosis of hepatic stellate cells. The hepatic stellate cells were divided into a blank control group, a transforming growth factor-β1(TGF-β1)(10 ng·mL~(-1)) group, and low-(12.5 mg·L~(-1)), medium-(25 mg·L~(-1)), and high-dose(50 mg·L~(-1)) curcumol groups. The effect of curcumol on the viability of hepatic stellate cells induced by TGF-β1 was detected by the MTT assay kit. The apo-ptosis in each group was determined by flow cytometry. Real-time fluorescence-based quantitative PCR(RT-PCR) was employed for the detection of mRNA expression of α-smooth muscle actin(α-SMA), type Ⅰ collagen(collagen Ⅰ), and type Ⅲ collagen(collagen Ⅲ). Western blot was used to detect the protein expression of p62, microtubule-associated protein 1 light chain 3(LC3), beclin1, B cell lymphoma 2(Bcl-2), and Bcl-2-associated X protein(Bax). Transmission electron microscopy(TEM) was used to observe cell morphology and autophagosome formation in each group. The autophagic flux was observed after cell infection with adenovirus under double fluorescence labeling. The cell viability assay revealed that compared with the TGF-β1 group, the curcumol groups showed significantly decreased cell viability. The apoptosis assay showed that the apoptosis rates of the curcumol groups were significantly higher than that of the TGF-β1 group. RT-PCR indicated that the mRNA expression of α-SMA, collagenⅠ, and collagen Ⅲ in the curcumol groups was significantly lower than that of the TGF-β1 group. Western blot showed that the expression of p62, LC3, beclin1, Bcl-2, and Bax in the curcumol groups was significantly different from that in the TGF-β1 group. As demonstrated by TEM, compared with the TGF-β1 group, the curcumol groups showed significantly increased autophagosomes. The detection of autophagic flow by the adenovirus under double fluorescence labeling showed that autolysosomes in the curcumol groups were significantly increased compared with those in the TGF-β1 group. Curcumol can induce the autophagy and apoptosis of hepatic stellate cells, which may be one of its anti-liver fibrosis mechanisms.

Cloning and function analysis of chalcone isomerase gene and chalcone synthase gene in Lonicera macranthoides / 中国中药杂志

In order to explore the functions of genes of key rate-limiting enzymes chalcone isomerase(CHI) and chalcone synthase(CHS) in the biosynthesis of flavonoids in Lonicera macranthoides, this study screened and cloned the cDNA sequences of CHI and CHS genes from the transcriptome data of conventional variety and 'Xianglei' of L. macranthoides. Online bioinformatics analysis software was used to analyze the characteristics of the encoded proteins, and quantitative reverse-transcription polymerase chain reaction(qRT-PCR) to detect the expression of CHI and CHS in different parts of the varieties at different flowering stages. The content of luteo-loside was determined by high performance liquid chromatography(HPLC) and the correlation with the expression of the two genes was analyzed. The results showed that the CHI and CHS of the two varieties contained a 627 bp and 1170 bp open reading frame(ORF), respectively, and the CHI protein and CHS protein were stable, hydrophilic, and non-secretory. qRT-PCR results demonstrated that CHI and CHS of the two varieties were differentially expressed in stems and leaves at different flowering stages, particularly the key stages. Based on HPLC data, luteoloside content was in negative correlation with the relative expression of the genes. Thus, CHI and CHS might regulate the accumulation of flavonoids in L. macranthoides, and the specific functions should be further studied. This study cloned CHI and CHS in L. macranthoides and analyzed their expression for the first time, which laid a basis for investigating the molecular mechanism of the differences in flavonoids such as luteoloside in L. macranthoides and variety breeding.

Application value of lung ultrasound in the diagnosis and severity assessment of ventilator-associated pneumonia / 中华危重病急救医学

Objective:To explore the value of bedside lung ultrasound in the early diagnosis and severity assessment of ventilator-associated pneumonia (VAP).Methods:A prospective observational study was conducted in 60 patients with VAP (VAP group) and 62 patients without VAP (control group) who were admitted to department of intensive care unit of General Hospital of Ningxia Medical University from September 2018 to July 2020. The gender, age and underlying diseases of non-VAP group were matched with VAP group. The general clinical data such as gender, age, underlying diseases, department source of the patient, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, sequential organ failure assessment (SOFA) score were recorded. The body temperature, white blood cell count (WBC), procalcitonin (PCT), oxygenation index (PaO 2/FiO 2), alveolar artery oxygen differential pressure (P A-aDO 2) were recorded. During mechanical ventilation, the patient's body temperature, WBC, sputum characteristics, and the change of the lung ultrasound were dynamically observed. With or without dynamic air bronchogram, lung ultrasound was considered to be positive as long as there were small subpleural consolidation or tissue-like sign. Ventilator-associated pneumonia lung ultrasound score (VPLUS) and lung ultrasound score (LUSS) were performed, and chest CT scan was completed on the same day. Use positive chest CT scan as the standard to evaluate the diagnostic efficacy of lung ultrasound, VPLUS score, and the combination of the two with PCT for VAP. LUSS was used to assess the severity of disease in patients with VAP. The correlation between LUSS and PaO 2/FiO 2, P A-aDO 2, APACHEⅡscore and SOFA score were analyzed. Results:① General information: compared with non-VAP group, VAP group had more emergency surgery patients [51.7% (31/60) vs. 33.9% (21/62), P = 0.047], APACHEⅡ score and SOFA score were significantly higher (APACHEⅡscore: 15.4±5.7 vs. 13.4±3.4, P = 0.021; SOFA score: 8.8±4.2 vs. 6.3±3.3, P < 0.001), body temperature tended to rise (℃: 38.3±0.8 vs. 38.0±0.9, P = 0.054), more patients had airway purulent secretions [65.0% (39/60) vs. 41.9% (26/62), P = 0.011], and mechanical ventilation time and length of ICU stay were longer [mechanical ventilation time (days): 10.5 (6.6, 15.0) vs. 4.3 (3.0, 6.0), P < 0.001; length of ICU stay (days): 14.8 (9.0, 18.0) vs. 6.0 (4.0, 9.1), P < 0.001], 28-day mortality rate was higher [31.7% (19/60) vs. 9.7% (6/62), P = 0.003].② Diagnostic efficacy evaluation: when lung ultrasound was positive, VPLUS≥3 and PCT > 0.5 μg/L were used separately for the diagnosis of VAP, the sensitivity was 73.3%, 75.0%, 61.7%, respectively; the specificity was 80.6%, 58.1% and 59.7%, respectively; the 95% confidence interval (95% CI) was 0.685-0.842, 0.574-0.748, 0.514-0.694, respectively, all P < 0.05, positive lung ultrasound had good sensitivity and specificity. When positive lung ultrasound or VPLUS≥3 were combined with PCT > 0.5 μg/L for tandem test, the specificity of VAP diagnosis was increased to 95.2% and 83.9%, respectively; but the specificity of VAP diagnosis of positive lung ultrasound combined with PCT > 0.5 μg/L was higher than VPLUS ≥3 combined with PCT > 0.5 μg/L (95.2% vs. 83.9%, P < 0.05).③ Correlation analysis: LUSS showed a significant positive correlation with APACHEⅡ and SOFA score ( r values were 0.407, 0.399, P values were 0.001, 0.002, respectively), LUSS had no relation with PaO 2/FiO 2 and P A-aDO 2 ( r values were 0.189, -0.064, P values were 0.629, 0.149, respectively). Conclusions:Lung ultrasound can early detect VAP , and its diagnostic specificity is significantly improved when combined with PCT > 0.5 μg/L. LUSS is closely related to the severity of disease in VAP patients, therefore, lung ultrasound may be an effective method for early diagnosis and efficacy evaluation of VAP patients.

Clinical characteristics and risk factors for mortality analysis of 94 cases of rheumatic diseases with pneumomediastinum / 中华风湿病学杂志

Objective:To analyze the clinical characteristics and risk factors of rheumatic diseases complicated with Pneumomediastinum (PnM).Methods:A retrospective analysis of 94 inpatients with rheumatic diseases associated PnM from Peking Union Medical College Hospital and Shanxi Bethune Hospital between January 1998 and October 2018 was carried out. Patients were divided into idiopathic inflammatory myopathies (IIM) and the non-IIM group. Clinical features, laboratory examinations and treatment were compared between the two groups. Cox proportional hazard model was used to investigate the risk factors for prognosis.Results:A total of 94 patients were included in the study, with an average age of (45±14) years. Forty-five (48%) of them were male. There were 62 patients in the IIM group and the other 32 were in the non-IIM group. Sixty-nine patients had predisposing factors before PnM. Severe cough and assisted mechanical ventilation were the most common causes. Compared with the non-IIM group, the incidence of digital vasculitis (29% vs 6%, χ2=6.540, P=0.008), arthritis (60% vs 28%, χ2=8.409, P=0.004), interstitial lung disease (ILD)(98% vs 78%, χ2=11.129, P=0.002) were higher in the IIM group, treatment with cyclophosphamide was higher in the IIM group ( χ2=4.458, P=0.035). There was non-significant difference in mortality between the two groups during hospitalization (50% vs 59%) and 6 months after PnM (64% vs72%) ( P>0.05). Pulmonary infection was the only risk factor for poor prognosis [ HR=3.131, 95% CI (1.025, 9.561), P=0.045], in which bacteria infection was the most common cause (65/75, 86.7%). Conclusion:PnM is a severe complication of rheumatic diseases. To get a good prognosis, rheumatol-ogists should balance the benefit and risk of infection of immunosuppressive therapy.

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death

Background/Aims@#Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. @*Methods@#Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). @*Results@#Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. @*Conclusions@#Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

Current situation and problems of national standards for Chinese medicinal materials / 中国中药杂志

To learn the current situation and strengthen the management of national standards for Chinese medicinal materials, we sorted out the relevant national standards. According to incomplete statistics, there are 1 185 kinds of Chinese medicinal materials, including 1 024 kinds of plant medicines, 106 kinds of animal medicines, and 54 kinds of mineral medicines, in addition to ethnic medicinal materials with different functions. The relevant standards include 819 Pharmacopoeia standards, 342 standards issued by the Ministry of Health or National Medicinal Products Administration, 7 standards for new medicinal materials, and 17 standards for imported medicinal materials. In this paper, the sources of standards as well as the distribution of families and genera and the distribution of medicinal parts of medicinal materials are analyzed. The suggestions are as follows:(1)to improve the coordination among different national standards of Chinese medicinal materials;(2)to improve the standardization and controllability of relevant standards;(3)to revise the issued standards for Chinese medicinal materials(including Tibetan, Uygur, and Mongolian medicinal materials).

L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction

Background/Aims@#Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. @*Methods@#Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. @*Results@#LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. @*Conclusions@#LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

The Inhibiting Effect of Autophagy Inhibitor ROC-325 on Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of autophagy inhibitor ROC-325 and its combination with bortezomib on the proliferation, apoptosis and autophagy of multiple myeloma cell lines.@*METHODS@#Multiple myeloma cells were treated with ROC-325 at different concentration. The cell proliferation was detected by CCK-8. Apoptosis was determined by Caspase-3/7 and Caspase-9 activity assays. Autophagy was detected by monodansylcadaverine staining. The apoptosis-related proteins (PARP and Caspase-3) and autophagy-related proteins (P62, Beclin-1, and LC3A/B) were analyzed by Western blot. The combined effect with bortezomib on bortezomib-resistant cell line was detected by CCK-8.@*RESULTS@#ROC-325 inhibited the proliferation of RPMI 8226, RPMI 8226-BTZ100, U266 and IM9 cells in a dose-dependent manner (r=-0.8275, r=-0.9079, r=-0.9422, r=-0.9305), the 72 h IC@*CONCLUSION@#ROC-325 can inhibit the proliferation, induce the apoptosis of myeloma cells through the mitochondrial pathway, inhibit the autophagy of myeloma cells by affecting the fusion of autophagosomes and lysosomes, and overcome bortezomib resistance by the combination of ROC-325 with bortezomib.

Impact of microRNA / 中南大学学报(医学版)

OBJECTIVES@#To explore the molecular mechanism for thyroid cancer metastasis via analyzing the role of microRNA (miR)-21-5p and its target gene recombinant sclerostin domain containing protein 1 (SOSTDC1) in thyroid cancer.@*METHODS@#The target miR-21-5p was screened through bioinformatics analysis and cell verification, and the thyroid cancer cell lines was transfected with miR-21-5p inhibitor. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, flow cytometry, and cell scratch test were used to detect the proliferation, apoptosis and migration of thyroid cancer cells in the miR-21-5p inhibitor group and the inhibitor control group, respectively. The luciferase report experiment was used to verify the relationship between miR-21-5p and SOSTDC1, Western blotting was used to detect the expression levels and phosphorylation levels of SOSTDC1,phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt) and mitogen-activated protein kinases (MAPK), extracellular regulated protein kinases (ERK) in thyroid cancer cells.@*RESULTS@#MiR-21-5p was significantly increased in thyroid cancer cells,which was negatively correlated with SOSTDC1 (@*CONCLUSIONS@#MiR-21-5p in thyroid cancer cells can target the expression of SOSTDC1 and affect the activities of PI3K/Akt and MAPK/ERK, thereby inhibiting the apoptosis of thyroid cancer cells and promoting cell proliferation and migration.

Anti-anaphylactic potential of benzoylpaeoniflorin through inhibiting HDC and MAPKs from Paeonia lactiflora / 中国天然药物

Guided by cell-based anti-anaphylactic assay, eighteen cage-like monoterpenoid glycosides (1-18) were obtained from the bioactive fraction of P. lactiflora extract. Among these, compounds 1, 5, 6, 11, 12, 15, and 17 significantly reduced the release rate of β-HEX and HIS without or with less cytotoxicity. Furthermore, the most potent inhibitor benzoylpaeoniflorin (5) was selected as the prioritized compound for the study of action of mechanism, and its anti-anaphylactic activity was medicated by dual-inhibiting HDC and MAPK signal pathway. Moreover, molecular docking simulation explained that benzoylpaeoniflorin (5) blocked the conversion of L-histidine to HIS by occupying the HDC active site. Finally, in vivo on PCA using BALB/c mice, benzoylpaeoniflorin (5) suppressed the IgE-mediated PCA reaction in antigen-challenged mice. These findings indicated that cage-like monoterpenoid glycosides, especially benzoylpaeoniflorin (5), mainly contribute to the anti-anaphylactic activity of P. lactiflora by dual-inhibiting HDC and MAPK signal pathway. Therefore, benzoylpaeoniflorin (5) may be considered as a novel drug candidate for the treatment of anaphylactic diseases.

Research advances in repair of growth plate injury / 中华创伤骨科杂志

Growth plate,the developmental center of endochondral osteogenesis,can be divided morphologically and functionally into a resting zone,a proliferative zone,a prehypertrophic zone and a hypertrophic zone.Injuries to growth plate often lead to bone growth defects including limb length discrepancy and angulation deformity in children.Currently,their orthopedic corrective surgeries are invasive and limitedly effective and no effective biotherapy has been available.Previous studies on animal models of growth plate damage have investigated the related cellular and molecular events in the repair of damaged growth plates in the 4 distinct inflammatory,fibrogenic,osteogenic and remodeling phases.Related molecules involved in the regulation of the above processes,such as inflammatory cytokines tumor necrosis factor alpha,mitogenic platelet-derived growth factor and bone morphogenetic protein,are found to participate in the regulation of growth plate injury.Exploration of the mechanisms may provide new targets for biotherapy.In addition,development of cartilage tissue engineering,especially application of mesenchymal stem cells,also provides potential interventions for growth plate injury.

Cloning and Expression Patterns of LmC3H1 Gene in Lonicera macranthoides and Its Correlation with Chlorogenic Acid Content / 中国实验方剂学杂志

Objective::To clone p-coumaroyl quinate/shikimate 3' -hydroxylase gene from Lonicera macranthoides, and analyze its bioinformatics and expression patterns with chlorogenic acid content, in order to speculate the functions of LmC3H1 gene from L. macranthoides. Method::The full-length cDNA sequence of LmC3H1 gene was cloned by reverse trascription polymerase chain reaction(RT-PCR) and RACE techniques. The bioinformatics analysis of the gene sequence was carried out by using relevant software.Real-time fluorescence quantification PCR(Real-time PCR) and HPLC were used to determine relative expression of LmC3H1 and content of chlorogenic acid in stems, leaves and flowers of different flowering stages. Result::The LmC3H1 (GenBank: MN177695) gene was cloned, and the open reading frame (ORF) of it was 1 533 bp in length and encoded 510 amino acids. The molecular formula was C2618H4134N718O727S22, the relative molecular mass was 58 005.32, and the isoelectric point was 8.92.It was a hydrophilic protein located in the chloroplast with a transmembrane region LLLIPAVLFLISLVYPLI, and contained a conserved domain CYTOCHROME_P450(433-422 aa) in cytochrome P450.The results of Real-time PCR showed that LmC3H1 was expressed in different degrees in stems, leaves and different flowering stages of L. macranthoides. In the flower development stage, the relative expression of white bud stage was the highest, followed by flower buds and white flowering stage. The ratio of flower to stem and leaf was the highest, and the relative expression of flower was the highest. The HPLC results showed that the content of chlorogenic acid increased from greenish white to golden yellow in flowering stage and golden yellow flowering stage. Among the different organs, the flower had the highest chlorogenic acid, and the stem showed the lowest. Conclusion::The LmC3H1 gene of L. macranthoides is cloned, suggesting that LmC3H1 might be involved in the biosynthesis of L. macranthoides chlorogenic acid. This study provides a basis for further studying the functions of the gene and exploring the biosynthesis and regulation mechanism of L. macranthoides chlorogenic acid, while laying the foundation for the genetic improvement of L. macranthoides.

Study on the Medical Insurance Budget Impact Analysis Guideline in Some European Countries and Its Enligh- tenment to China / 中国药房

OBJECTIVE：To study the m edical insurance budget impact analysis （BIA）guidelines or nomative documents of some European countries ，and to provide the suggestions for the formulation and implementation of medical insurance BIA guidelines in China. METHODS ：Medical insurance BIA guidelines or related documents in European countries such as Ireland ， France，Poland，Belgium and UK were retrieved to summarize and comparatively analyze the general analysis framework and special specification. The formulation of medical insurance BIA guideline in China and the suggestions were put forward. RESULTS & CONCLUSIONS ：The above-mentioned medical insurance BIA guidelines or documents of the five European countries generally study the impact of the cost of health technology on resources within 3-5 years from the perspective of budget holders. The analysis framework of the guidelines or documents is basically the same ，but the guidelines or documents are adjusted according to the characteristics of national health system in terms of the positioning of medical insurance BIA ，the scope of cost data inclusion ， model design ，population subgroup analysis and so on. For example ，Ireland had special requirements on cost data inclusion ， sensitivity analysis and data source ，while France had detailed regulations on medical insurance BIA model ，sensitivity analysis and presentation of medical insurance BIA results. Our country should pay attention to the role of medical insurance BIA in medical and health decision-making ，formulate China ’s medical insurance BIA guidelines to standardize empirical research ，and combine the characteristics of China ’s health system when formulate the guideline. It is suggested that China ’s medical insurance BIA guidelines should at least include research perspective ，research time limit and discount ，reference situation ，target population ， cost，market share ，data source ，uncertainty analysis and other overall framework or basic elements to ensure the smooth operation of medical and health funds.