Protective mechanism of Tangshenbao on kidney of diabetic nephropathy rats / 国际中医中药杂志

Objective:To investigate the protective effect and possible mechanism of Tangshenbao on renal damage in diabetic nephropathy (DN) rats.Methods:Totally 36 SPF male SD rats were randomly divided into normal group ( n=6) and model group ( n=30). The DN rat model was prepared by single high-dose intraperitoneal injection of STZ. According to the random number table method, the rats were divided into model group, irbesartan group and Tangshenbao low-, medium- and high-dosage groups, with 6 rats in each group. Drug intervention lasted for 8 weeks. The general condition and body weight of rats in each group were recorded. The blood glucose, kidney index, 24 h urine protein (24 h UTP), SCr and BUN levels were detected. The pathological morphology of renal tissue was observed by PAS staining and transmission electron microscopy. The mRNA and protein expressions of Ets-1, TGF-β1, Smad2 and Smad3 in renal tissue were detected by real-time fluorescence quantitative PCR and Western blot. Results:Compared with model group, the body weight of Tangshenbao low, medium and high dose groups and irbesartan group significantly increased ( P<0.01). The kidney index decreased ( P<0.05 or P<0.01). The contents of 24 hUTP, BUN and SCr significantly decreased ( P<0.05 or P<0.01). Glomerular volume was significantly reduced ( P<0.05 or P<0.01), the mRNA expressions of Ets-1 (1.59 ± 0.06, 1.47 ± 0.04, 1.31 ± 0.03, 1.39 ± 0.03 vs. 1.64 ± 0.04), TGF-β1 (1.65 ± 0.05, 1.59 ± 0.03, 1.38 ± 0.05, 1.49 ± 0.04 vs. 1.77 ± 0.08), Smad2 (1.48 ± 0.05,1.39 ± 0.05, 1.22 ± 0.03, 1.31 ± 0.04 vs. 1.54 ± 0.05), Smad3 (1.57 ± 0.04, 1.48 ± 0.03, 1.28 ± 0.03, 1.39 ± 0.02 vs. 1.64 ± 0.05) in renal tissue of rats significantly decreased ( P<0.05 or P<0.01), the protein expressions of Ets-1 (1.33 ± 0.32, 1.16 ± 0.38, 0.77 ± 0.06, 0.84 ± 0.06 vs. 1.97 ± 0.43), TGF-β1 ( 1.35 ± 0.14, 1.24 ± 0.22, 0.94 ± 0.13, 1.07 ± 0.06 vs. 1.63 ± 0.20), Smad2 (1.24 ± 0.26, 1.14 ± 0.31, 0.77 ± 0.28, 0.85 ± 0.19 vs. 1.72 ± 0.34) and Smad3 (1.29 ± 0.14, 1.19 ± 0.21, 0.85 ± 0.39, 0.90 ± 0.37 vs. 1.76 ± 0.21) decreased ( P<0.05 or P<0.01). Conclusion:Tangshenbao can improve renal damage in DN rats, and its mechanism may be related to the inhibition of Ets-1 expression and TGF-β1/Smads signaling pathway.

Application of metagenomic next-generation sequencing in patients with Herpes simplex pneumonia mixed infection / 中国医师杂志

Objective:To explore the application value of next-generation sequencing (mNGS) technology in patients with Herpes simplex pneumonia mixed infection.Methods:The clinical data of pneumonia patients who underwent alveolar lavage fluid mNGS technology and traditional pathogen detection in the Affiliated Hospital of Yangzhou University from June 2018 to January 2021 were retrospectively collected.Results:A total of 41 patients with mNGS Herpes simplex type 1 (HSV-1) test (4 HSV-1 carriers, 37 HSV-1 infections) were enrolled in this study, including 22 males and 19 females. The age ranged from 46 to 83 years old, with a median age of 67 years. The higher proportion of pathogens in 25 cases of HSV-1 co-infection detected by mNGS were Pneumocystis jiroveci (6 cases, 24.0%), Acinetobacter baumannii (4 cases, 16.0%), and Klebsiella pneumoniae (4 cases, 16.0%), and Aspergillus fumigatus (3 cases, 12.0%). The difference in the Simpson's diversity index in the HSV-1carrier group, HSV-1 single infection group and HSV-1 mixed infection group was statistically significant ( P<0.05). Compared with 12 cases of HSV-1 single infection, the time for body temperature to return to normal for 25 cases of HSV-1 mixed infection was [(5.16±2.04)days vs (3.75±1.29)days], and course of antibiotic treatment was longer [(10.60±2.18)d vs (8.92±1.98)d]. Conclusions:The mNGS technology has obvious advantages in identifying HSV-1 mixed infections, which is beneficial to physicians to treat them accurately.

Development of a mouse model of stellate ganglion block and subsequent effects on cerebral cortical blood flow / 中华麻醉学杂志

Objective:To develop a model of stellate ganglion block (SGB) in mice and investigate the effect of SGB on cerebral cortical blood flow.Methods:Thirty clean-grade healthy male C57BL/6 mice, aged 8-9 weeks, weighing 23-27 g, were divided into 5 groups ( n=6 each) using a random number table method: control group (group C), left SGB group (group L), left normal saline group (group SL), right SGB group (group R) and right normal saline group (group SR). Group C received no intervention.SGB was performed with 0.25% ropivacaine 0.08 ml via percutaneous posterior approach in L and R groups, while the equal volume of normal saline 0.08 ml was given instead at the location of left and right stellate ganglion in SL and SR groups, respectively.The cerebral cortical blood flow was determined using laser speckle contrast imaging system before SGB (T 0) and at 10, 30, 60, 90 and 120 min after SGB (T 1-5). Results:Mice developed ptosis on the block side, indicating that the model of SGB was successfully developed in L and R groups.There was no significant difference in cerebral cortical blood flow at each time point among C, SL and SR groups ( P>0.05), and cerebral cortical blood flow on the block side decreased at T 1, began to increase at T 2, peaked at T 3, and decreased at T 5 which was still higher than that at T 0 in group L and group R ( P<0.01). Compared with C and SL groups, the left cerebral cortical blood flow was significantly decreased at T 1, 5 and increased at T 2-4 in group L ( P<0.01). Compared with C and SR groups, the right cerebral cortical blood flow was significantly decreased at T 1, 5 and increased at T 2-4 in group R ( P<0.01). There were no significant differences in cerebral cortical blood flow at each time point between group C and group SL and between group C and group RL ( P>0.05). Conclusions:The mouse model of SGB via percutaneous posterior approach is successfully developed.Unilateral SGB can affect cerebral cortical blood flow on the block side, which shows a transitory decrease followed by a sustained significant increase.

Effect of the completion time of initial 30 mL/kg fluid resuscitation on the prognosis of patients with septic shock / 中华危重病急救医学

Objective:To investigate the effect of the completion time of initial 30 mL/kg fluid resuscitation on the prognosis of patients with septic shock.Methods:An observational study was conducted. The inpatients with septic shock admitted to intensive care unit (ICU) of Northern Jiangsu People's Hospital, Affiliated Hospital of Yangzhou University and Jiangdu People's Hospital from October 1st, 2018 to September 30th, 2020 were enrolled. The general data including gender, age, body mass index (BMI), patient source, site of infection, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score and arterial blood lactic acid (Lac) at ICU admission, fluid resuscitation dose, completion time of initial 30 mL/kg fluid resuscitation, mechanical ventilation, incidence of acute kidney injury (AKI), continuous renal replacement therapy (CRRT), length of ICU stay and 28-day mortality. The relationship between the completion time of initial 30 mL/kg fluid resuscitation and ΔSOFA score (the difference between SOFA score 3 hours of fluid resuscitation and initial SOFA score) was analyzed. In addition, according to the completion time (T) of initial 30 mL/kg fluid resuscitation, the patients were divided into T ≤ 1 hour group, 1 hour < T≤2 hours group, 2 hours < T≤3 hours group and T > 3 hours group, and the observation parameters among the groups were compared.Results:① A total of 131 patients were enrolled, including 94 males and 37 females with an average age of (68.3±15.0) years old. The median APACHE Ⅱ score was 27 (21, 34), the median of initial SOFA score was 12 (10, 14), the median of initial Lac was 5.0 (3.4, 7.1) mmol/L, and the most common source of infection was lung, with a total of 87 patients (66.41%). The completion time of initial 30 mL/kg fluid resuscitation and ΔSOFA score fitted the Logistic curve ( Y = -1.062 6 X2+4.407 9 X+0.961 8), which suggested that the early or late completion time of initial fluid resuscitation had adverse effects on the prognosis of patients with septic shock.② There was no significant difference in infection site, initial APACHE Ⅱ score, initial Lac, and initial SOFA score among different completion time of initial 30 mL/kg fluid resuscitation groups. The respiratory support rate, the incidence of AKI and the ratio of CRRT in the T ≤1 hour group were significantly higher than those in the 1 hour < T≤2 hours group, 2 hours < T≤3 hours group and T > 3 hours group (respiratory support rate: 78.57% vs. 75.51%, 42.86%, 75.00%; incidence of AKI: 57.14% vs. 20.41%, 21.43%, 50.00%; ratio of CRRT: 35.71% vs. 0%, 7.14%, 16.67%), the differences among the groups were statistically significant (all P < 0.05). The 28-day mortality was the highest in the T ≤ 1 hour group (64.29%), and the lowest in the 1 hour < T ≤2 hours group (22.45%), 35.71% in the 2 hours < T ≤ 3 hours group, 33.33% in the T > 3 hours, and the difference among the groups was statistically significant ( P < 0.01). Conclusions:Completion of initial 30 mL/kg fluid resuscitation in 1-2 hours after septic shock may reduce the 28-day mortality and improve organ dysfunction, and initial fluid resuscitation prematurely or too late may increase 28-day mortality. But further research and verification are needed.

Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway / 神经科学通报·英文版

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway / 神经科学通报·英文版

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

Application of alveolar lavage fluid metagenomic next-generation sequencing in patients with severe pneumonia of unknown pathogen / 中国基层医药

Objective:To evaluate the application value of metagenomic next-generation sequencing(mNGS) for patients with severe pneumonia of unknown pathogen.Methods:The clinical data of 8 patients with unknown pneumonia pathogens who were assisted by the alveolar lavage fluid mNGS technology treated in Affiliated Hospital of Yangzhou University from June 2019 to February 2020 were retrospectively analyzed, including alveolar lavage fluid smear, culture, and the sequencing result.The clinical characteristics and mNGS detection results were comprehensively analyzed.According to the results of mNGS and the judgment of the clinician, the patients were divided into confirmed pathogens group and undetermined pathogens group, and the Simpson's diversity index of two groups was compared.Results:Among 8 cases, there were 5 males and 3 females, and the median age was 62.5 years (ranged from 41 to 71 years). All of them had chronic diseases except 1 case, including diabetes, chronic obstructive pulmonary disease and kidney transplantation.mNGS was positive in 8 patients, and conventional test was positive in 3 patients.The comparison of the Simpson's diversity index between the identified pathogenic group and the undetermined pathogenic group showed statistically significant difference [(0.398 ± 0.222) vs.(0.763 ± 0.061), t=2.709, P=0.035]. The positive results of mNGS were different from that of conventional test in 2 patients.The nucleic acid number in 3 cases of Pneumocystis carinii with mNGS positive results ranged from 120 to 15 580, with genomic coverage rates from 24.6% to 99.8%. Conclusion:mNGS can help physicians acquire information of the pathogenic bacteria quickly and comprehensively, especially for patients with unknown pneumonia pathogenic bacteria.

The prognostic value of circulating microRNA-29b in left ventricular hypertrophy in patients with hypertension / 中华内科杂志

Objective To analyze the relationship between the level of microRNA-29b in circulation and left ventricular hypertrophy in hypertensive patients.Methods A total of 240 subjects from Henan Province People's Hospital from June 2015 to June 2018 were included in the present study.Among them,160 were hospitalized patients,and were divided into two groups.Patients with simple hypertension and had no left ventricular hypertrophy (80 cases) were in the simple hypertension group (HBP-NLVH),and patients with hypertension combined with left ventricular hypertrophy (80 cases) were in the high blood pressure with left ventricular hypertrophy group (HBP-LVH).Normal control subjects (80 cases) were those with no hypertension and randomly selected from the medical center of Henan Province People's Hospital.Serum microRNA-29b expressions were detected by real time fluorescence quantitative PCR.The thickness of interventricular septum (IVSD) and left ventricular posterior wall thickness (LVPWD) were measured by echocardiography.Results Compared with the normal control group (1.95±0.79),the relative expression of microRNA-29b in the patients both in the HBP-NLVH group (2.67±0.92) and the HBP-LVH group (5.12 ± 1.23) was up-regulated,and the difference between normal control and patients was statistically significant (P＜0.05).In patients,the microRNA-29b level in the HBP-LVH group was significantly higher than that in the HBP-NLVH group (P＜0.05).The expression level of microRNA-29b was positively correlated with IVSD (r=0.71,P＜0.05) and LVPWD (r=0.74,P＜0.05),respectively.The sensitivity and specificity of serum microRNA-29b levels in the diagnosis of left ventricular hypertrophy in hypertension patients were 96.8％ and 91.3％,respectively.Conclusion Serum microRNA-29b level is elevated in hypertensive patients with left ventricular hypertrophy,and is positively correlated with left ventricular hypertrophy.The circulation microRNA-29b might be a useful biomarker with prognostic value in left ventricular hypertrophy in hypertension patients.

Analysis of pressure-time and flow-time curve in ventilator / 中华危重病急救医学

Objective To better understand the significance of the pressure-time curve and flow-time curve from the perspective of PB840 ventilator working principle. Methods ① Mechanical principle: flow supply valves (air valve and oxygen valve) and exhalation valve in PB840 ventilator were controlled to achieve the ventilation target (volume or pressure) by the central processing unit according to the monitoring data from pressure sensors (P1 at the supply side, P2 at the exhalation side) and flow sensors (Q1 at the air side, Q2 at the oxygen side, Q3 at the exhalation side). ② The essence of curve: each point means a value of pressure or flow at a certain time measured by the sensors or calculated by the system. ③ The respiratory process could be divided into inspiratory part, expiratory part, and the connection part from expiratory to inspiratory. The air running state and the respiratory mechanics relationship at the three parts could be inferred according to the form of curves. Results ① Inspiratory process: at volume-controlled and constant flow ventilation: there should be a relationship "Pc-Pa = XR" between alveolar pressure (Pa) and circuit pressure (Pc) according to Ohm law. So, the Pc curve (pressure-time curve) could indirectly reflect the Pa curve with the flow (X) and resistance (R) being constant. At pressure-set ventilation: it is the goal of ventilator to maintain the Pc at the target level. So, the stability of the target pressure line in pressure-time curve reflects the matching ability of the flow supply valves and the exhalation valve. ② Expiratory process: it could be divided into pre-expiratory [without basicflow (Ba) or bias flow (Bi)] and post-expiratory (with Ba or Bi), where Ba or Bi is equal to "Q1+Q2". So, the mathematical function are "X(t) = Q3t" in pre-part, and "X(t) = Q3t-(Q1t+Q2t)" in post-part. The relationship between pressure and flow at peak expiratory flow point: it could be found that there is an obvious time span and area formation under the curve from 0 to peak point (Fpeak) after stretching the abscissa axis of flow-time curve. It means that some gas have been discharged from the lung when it arrives at the peak point. So, the alveolar pressure should be lower than the platform pressure at the point (Pplat). The circuit pressure is significantly higher than positive end expiratory pressure (PEEP) at the point in the stretching axis diagram. So, it means that the formula "RE = (Pplat-PEEP)/Fpeak" to calculate the expiratory resistance (RE) is unreasonable in the angle of Ohm law. ③ The process from exhalation to inspiratory: according to the difference of the starting point of the conversion, it could be divided into two cases: one is that the inspiratory started from the ending of exhalation. Here, the inhaling starting point is lying in the abscissa axis. The other is that the inspiratory started before the ending of exhalation (with endogenous positive end expiratory pressure). Here, the starting point is lying below the abscissa axis, and the slope of the following curve is obviously larger than the slope of natural expiratory curve. According to the difference of results from the starting point to the end of the inhalation triggering effort, it could be divided into two cases: one is that it reach the trigger point. Here, the expiratory curve extends upward from or below the horizontal axis until an effective air supply is triggered. The other is that it could not reach the trigger point. Here, the expiratory curve extends upward from or below the horizontal axis, but then runs downward (meaning exhaling). Conclusion It is helpful to analyze the ventilation state, ventilation failure, and the causes of man-machine confrontation with understanding the ventilation principle and the air route map of the ventilator.

Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice / 神经科学通报·英文版

The obstacle to successful remyelination in demyelinating diseases, such as multiple sclerosis, mainly lies in the inability of oligodendrocyte precursor cells (OPCs) to differentiate, since OPCs and oligodendrocyte-lineage cells that are unable to fully differentiate are found in the areas of demyelination. Thus, promoting the differentiation of OPCs is vital for the treatment of demyelinating diseases. Shikimic acid (SA) is mainly derived from star anise, and is reported to have anti-influenza, anti-oxidation, and anti-tumor effects. In the present study, we found that SA significantly promoted the differentiation of cultured rat OPCs without affecting their proliferation and apoptosis. In mice, SA exerted therapeutic effects on experimental autoimmune encephalomyelitis (EAE), such as alleviating clinical EAE scores, inhibiting inflammation, and reducing demyelination in the CNS. SA also promoted the differentiation of OPCs as well as their remyelination after lysolecithin-induced demyelination. Furthermore, we showed that the promotion effect of SA on OPC differentiation was associated with the up-regulation of phosphorylated mTOR. Taken together, our results demonstrated that SA could act as a potential drug candidate for the treatment of demyelinating diseases.

Analysis of pressure-time and flow-time curve in ventilator / 中华危重病急救医学

Objective@#To better understand the significance of the pressure-time curve and flow-time curve from the perspective of PB840 ventilator working principle.@*Methods@#① Mechanical principle: flow supply valves (air valve and oxygen valve) and exhalation valve in PB840 ventilator were controlled to achieve the ventilation target (volume or pressure) by the central processing unit according to the monitoring data from pressure sensors (P1 at the supply side, P2 at the exhalation side) and flow sensors (Q1 at the air side, Q2 at the oxygen side, Q3 at the exhalation side). ② The essence of curve: each point means a value of pressure or flow at a certain time measured by the sensors or calculated by the system. ③ The respiratory process could be divided into inspiratory part, expiratory part, and the connection part from expiratory to inspiratory. The air running state and the respiratory mechanics relationship at the three parts could be inferred according to the form of curves.@*Results@#① Inspiratory process: at volume-controlled and constant flow ventilation: there should be a relationship "Pc-Pa = XR" between alveolar pressure (Pa) and circuit pressure (Pc) according to Ohm law. So, the Pc curve (pressure-time curve) could indirectly reflect the Pa curve with the flow (X) and resistance (R) being constant. At pressure-set ventilation: it is the goal of ventilator to maintain the Pc at the target level. So, the stability of the target pressure line in pressure-time curve reflects the matching ability of the flow supply valves and the exhalation valve. ② Expiratory process: it could be divided into pre-expiratory [without basic flow (Ba) or bias flow (Bi)] and post-expiratory (with Ba or Bi), where Ba or Bi is equal to "Q1+Q2". So, the mathematical function are "X(t) = Q3t" in pre-part, and "X(t) = Q3t-(Q1t+Q2t)" in post-part. The relationship between pressure and flow at peak expiratory flow point: it could be found that there is an obvious time span and area formation under the curve from 0 to peak point (Fpeak) after stretching the abscissa axis of flow-time curve. It means that some gas have been discharged from the lung when it arrives at the peak point. So, the alveolar pressure should be lower than the platform pressure at the point (Pplat). The circuit pressure is significantly higher than positive end expiratory pressure (PEEP) at the point in the stretching axis diagram. So, it means that the formula "RE = (Pplat-PEEP)/Fpeak" to calculate the expiratory resistance (RE) is unreasonable in the angle of Ohm law. ③ The process from exhalation to inspiratory: according to the difference of the starting point of the conversion, it could be divided into two cases: one is that the inspiratory started from the ending of exhalation. Here, the inhaling starting point is lying in the abscissa axis. The other is that the inspiratory started before the ending of exhalation (with endogenous positive end expiratory pressure). Here, the starting point is lying below the abscissa axis, and the slope of the following curve is obviously larger than the slope of natural expiratory curve. According to the difference of results from the starting point to the end of the inhalation triggering effort, it could be divided into two cases: one is that it reach the trigger point. Here, the expiratory curve extends upward from or below the horizontal axis until an effective air supply is triggered. The other is that it could not reach the trigger point. Here, the expiratory curve extends upward from or below the horizontal axis, but then runs downward (meaning exhaling).@*Conclusion@#It is helpful to analyze the ventilation state, ventilation failure, and the causes of man-machine confrontation with understanding the ventilation principle and the air route map of the ventilator.

Analysis of adverse effects of infliximab treatment in 486 patients with Crohn's disease / 中华消化杂志

Objective To assess the safety of infliximab (IFX) treatment in patients with Crohn's disease(CD).Methods From January 2009 to May 2018,at inflammatory bowel disease (IBD) center of Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,486 CD patients received the treatment of IFX were enrolled and their clinical data were collected.Univariate and multivariate regression of binary logistic were performed for statistical analysis.Results The median follow-up duration was 31.1 months (12.0 months to 40.0 months).The median duration of IFX therapy was 13.0 months (7.0 months to 21.0 months).Among 486 patients,98 (20.16％) patients reported adverse effects,and 12 (2.47％) patients discontinued the therapy because of adverse effects.Acute infusion reaction was the most common adverse effect in CD patients who received IFX treatment accounting for 41.84％ (41/98) of all the adverse effects,and the incidence was 8.44％.Thirty-nine patients had mild and moderate infusion reaction,and all improved after symptomatic treatment (eight patients discontinued IFX therapy because of recurrent infusion reaction).Two patients developed severe infusion reaction as allergic shock,and both relieved after emergency rescue.Four patients developed late-phase allergic reactions.Among 486 patients,39 (8.02％) patients had infections,including infections of Clostridium difficile,cytomegalovirus,herpeszoster virus,Mycobacterium tuberculosis,and other opportunistic pathogens.There was no cases of infection related death.Thirty-six patients continued with IFX treatment after infection controlled.Among 486 patients,14 (2.88％) patients had severe infection,and all the cases improved after anti-infection treatment.Twenty-seven CD patients with hepatitis B virus (HBV) infection received anti-viral treatments,no active HBV infection was observed.Colon adenocarcinoma was found in one patient under colonoscopy at 22 months after discontinuation of IFX therapy.There were six patients with the history of benign tumors,and no evidence of recurrence,progress or malignancy during treatment.In terms of other rare adverse effects in 486 patients,there were eight (1.64％) patients with liver function injury,two (0.41％) patients with anemia,one (0.21％) patient with peripheral neuropathy,and four (0.82％) patients with skin lesion.Prolonged duration of IFX therapy,without combination of immune-suppressors and with increased baseline body mass index (BMI) were the risk factors of acute infusion reactions.Prolonged duration of IFX therapy and with low baseline albumin level were the risk factors of infections.Conclusions IFX is generally safe as the treatment for CD patients,and its adverse effects can be clinically controlled.Screening before therapy and monitoring during therapy may reduce the risks of adverse effects.

LRRC25 plays a key role in all-trans retinoic acid-induced granulocytic differentiation as a novel potential leukocyte differentiation antigen

Leukocyte differentiation antigens (LDAs) play important roles in the immune system, by serving as surface markers and participating in multiple biological activities, such as recognizing pathogens, mediating membrane signals, interacting with other cells or systems, and regulating cell differentiation and activation. Data mining is a powerful tool used to identify novel LDAs from whole genome. LRRC25 (leucine rich repeat-containing 25) was predicted to have a role in the function of myeloid cells by a large-scale "omics" data analysis. Further experimental validation showed that LRRC25 is highly expressed in primary myeloid cells, such as granulocytes and monocytes, and lowly/intermediately expressed in B cells, but not in T cells and almost all NK cells. It was down-regulated in multiple acute myeloid leukemia (AML) cell lines and bone marrow cells of AML patients and up-regulated after all-trans retinoic acid (ATRA)-mediated granulocytic differentiation in AML cell lines and acute promyelocytic leukemia (APL; AML-M3, FAB classification) cells. Localization analysis showed that LRRC25 is a type I transmembrane molecule. Although ectopic LRRC25 did not promote spontaneous differentiation of NB4 cells, knockdown of LRRC25 by siRNA or shRNA and knockout of LRRC25 by the CRISPR-Cas9 system attenuated ATRA-induced terminal granulocytic differentiation, and restoration of LRRC25 in knockout cells could rescue ATRA-induced granulocytic differentiation. Therefore, LRRC25, a potential leukocyte differentiation antigen, is a key regulator of ATRA-induced granulocytic differentiation.

Impact of timing of antibiotic bundle therapy on outcomes in septic shock patients: a multicenter retrospective investigation / 中华全科医师杂志

The clinical data of 372 patients with septic shock admitted in departments of critical care medicine of three Grade A tertiary hospitals from January 2013 to December 2015 were retrospectively reviewed,including 211 survival cases and 161 fatal cases.According to septic shock early goal-directed therapy implementation,117 patients received bundle therapy (bundle group),including 30 cases with bundle goal-fully achieved,and 87 cases with bundle goal-partly achieved;and 255 cases received conventional treatment (non-bundle group).Muhiple logistic regression analysis showed that the multiple organ dysfunction syndrome score,length of ICU stay and first time using of antibiotics were independent risk factors for prognosis of septic shock (P ＜ 0.05).There was no significant difference in case fatality rate between bundle group and non-bundle group (46.2％ vs.42.0％,P ＞ 0.05),while the fatality in bundle goal-fully achieved group(20.0％)was significantly lower than that of goal-partly achieved group (55.2％) and non-bundle group (42.0％) (P ＜ 0.05).Survival curve analysis showed that the medial survival time in bundle goal-fully achieved group was significantly higher than that in non-bundle group (19.4 vs.10.5 days,P ＜0.05) and that in control group plus goal-partly achieved group(19.4 vs.12.9 days,P ＜0.05).Multiple Logistic regression analysis showed that central venous oxygen saturation and antibiotics using within one hour were protective factors for prognosis of septic shock (P ＜ 0.05).The results indicate that antibiotic bundle treatment of all indicators up to standards could significantly reduce the mortality of septic patients and early antibiotics is important in bundle treatment.

Clinical value and toxicities of docetaxel plus capecitabine in the first line treatment of metastatic breast cancer / 国际肿瘤学杂志

Objective To evaluate the clinical value and toxicities of docetaxel plus capecitabine in the first-line treatment of metastatic breast cancer (MBC),and compare the outcomes among different molecular subtypes.Methods A total of 108 patients with MBC who received docetaxel plus capecitabine combination treatment between January 1,2012 and December 31,2015 in Bejing Chaoyang District Sanhuan Cancer Hospital were retrospectively analyzed,and 104 cases were available for evaluation.The clinicopathological characteristics,clinical value and toxicities of these patients were evaluated.Results The patients were divided into 3 molecular subtypes,among 104 patients,85 patients in Luminal subtype,14 patients in triple negative breast cancer (TNBC) subtype,and 5 patients in human epidermal growth factor receptor-2 (HER-2) over expression subtype.The treatment achieved objective responses (OR) in 55 patients (52.9％),and the disease control rate (DCR) was 88.5％,including complete response (CR) in 4 patients,partial response (PR) in 51 patients,stable disease (SD) in 37 patients,and progressive disease (PD) in 12 patients.In Luminal subtype,4 patients achieved CR,43 PR,33 SD,and 5 PD.In TNBC subtype,6 patients achieved PR,3 SD,5 PD.In the HER-2 over expression subtype,2 patients achieved PR,1 SD,2 PD.There was no significant difference in the short-term therapeutic effect among 3 molecular subtypes (x2 =4.429,P =0.106).As a result,the progression-free survival (PFS) of the 104 patients was 1.5-121.0 months,and the median PFS was 10.0 months.The median PFS was 11.0 months in Luminal subtype,4.0 months in TNBC subtype and 10.3 months in HER-2 over expression subtype,with a significant difference (x2 =7.510,P =0.006).The most common adverse events were hand-foot syndrome (HFS),nausea or vomiting,neutropenia,anaemia,diarrhea and so on.The incidence of grade 2/3 HFS was 44.2％ (46/104),and the grade 3/4 neutropenia was 39.4％ (41/104).Conclusion The first-line treatment of MBC using docetaxel plus capecitabine is effective,and the toxicities can be tolerable,especially in the Luminal subtype.

Study of the impact of CLPTM1L on radiosensitivity of lung cancer / 国际生物医学工程杂志

Objective To study the correlation of cleft lip and palate transmembrane 1 like(CLPTM1L)expression and radiosensitivity of lung cancer cells.Methods Thiazolyl blue tetrazolium bromide(MTT) and cell colony formation assays were used to determine cell growth and survival.Western Blot assay was employed to measure protein expression.Results The results demonstrated a negative correlation between the CLPTM1L expression level and radiosensitivity of lung cancer cells.A lower radiosensitivity in lung cancer cells containing high level of CLPTM1L expression,and vice versa.Enforced expression of CLPTM1L resulted in a significant reduction of radiosensitivity in lung cancer cells irradiated with γ-rays.On the contrary,a marked elevation of radiosensitivity was observed in lung cancer cells transfected with CLPTM1L siRNA.Conclusions CLPTM1L may be a novel target gene in mediating radiosensitivity of lung cancer cells.

A salivary biochemical analysis of recruits associated with suicidal ideation / 军事医学

Objective To investigate the harmless biochemical indicators for early screening of populations at high risk of suicide .Methods Seven hundred and twenty-seven new recruits were investigated according to self-rating idea of suicide scale (SIOSS) in the first month of recruitment in 2014.Twenty-five recruits (originally 27 recruits, but 2 recruits were absent from biochemical tests ) whose SIOSS scores were less than 12 were recognized as the suicidal ideation group. Another 25 recruits whose SIOSS scores were more than 12 were randomly selected as the control group .Saliva samples of the 50 recruits were collected for biochemical analysis after one month and three months of training , respectively .After three months of training , the SIOSS was also used for evaluation of suicidal ideation .Results After one-month training , the concentrations of Ca , Mg, amylase ( Amy ) and salivary acid ( SA ) in saliva were demonstrated to be statistically different between the suicidal ideation group and the control group ( P 0.05).After three-month training, the concentrations of Ca, Mg, Amy and SA in saliva between the two groups showed no significant difference (P>0.05).Conclusion After the first month training , changes in the biochemical compositions were found in the saliva of the screened recruits with suicidal ideation, which may be associated with the stress response of the body .The biochemical indicators in saliva lack specificity for suicidal ideation .

Percutaneous transluminal angioplasty and vacuum sealing drainage for patients with diabetic foot and arteriosclerosis obliteration of the lower extremity / 中华普通外科杂志

Objective To study the clinical efficacy of percutaneous transluminal angioplasty (PTA) and vacuum sealing drainage technique on patients with diabetic foot and arteriosclerosis obliteration of the lower extremity.Methods Sixty-four patients were divided into two groups.Group A (32 patients) were treated by traditional methods,while 32 patients in Group B treated by vacuum sealing drainage technique in addition to percutaneous transluminal angioplasty.Results One week after surgery,ABI in group A was 0.53 ±0.17 vs 0.85 ±0.27 in group B,P =0.00.Ulcer healing rate increased from 31.25％ in group A to 81.25％ in group B,P ＜0.01.The amputation rate decreased from 56.25％ in group A to 18.75％ in group B,P =0.00.Claudication distance extended and ulcer recurrence rate in group A was 40％,while in group B it was 0,P =0.00.Conclusion The combination of PTA and vacuum sealing drainage significantly improves the prognosis of patients with diabetic foot and arteriosclerosis obliteration of the lower extremity.

Ancient Classical Prescriptions Treating Middle and Advanced Primary Liver Cancer:A Meta-analysis of Randomized Controlled Trials / 中国中医药信息杂志

Objective To evaluate the efficacy of ancient classical prescriptions treating middle and advanced primary liver cancer.Methods Articles were searched from Pubmed, Embase, SCI, Cochrane Liarary and CNKI, VIP, WanFang Data, CBM databases. Randomized controlled trials about ancient classical prescriptions treating advanced primary liver cancer were collected. Results 17 studies were included, a total of 994 patients. The recent efficiency of ancient classical prescription combined with symptomatic therapy increased by 28% compared with single supportive and symptomatic therapy;the stable rate of life quality increased by 23%;the efficiency of TCM syndrome increased by 29%;the survival rates of 3 months, 6 months and 1 year increased by 16%, 36.7% and 58.5% respectively;the life quality score of later increased by 6.29 on average. Conclusion Ancient classical prescription combined with supportive and symptomatic therapy in advanced primary liver cancers is superior to single supportive and symptomatic therapy on recent efficiency, survival rate (3 months/6 months/1 year), quality of life and TCM syndrome. The conclusion of this study needs randomized controlled trials with larger samples, multicenter and high quality for further verification.

Study on Migration Model of Antioxidants in Food Contact Polypropylene Plastics / 分析化学

A PP plastic film for food packaging (0. 1 mm) was prepared by adding two antioxidants of 2,6-di-tert-butyl-4-methyl-phenol(BHT) and pentaerythritol tetrakis ( 3-( 3, 5-di-tert-butyl-4-hydroxyphenyl ) propionate)(Irganox 1010) with different concentrations into polypropylene (PP) resin, then mixing extrusion granulate by the double screw plastic extruder and hot pressing the film at 190℃. The migration amount of the two antioxidants in food simulants (95% ethanol) was determined by high performance liquid chromatography (HPLC) with diode array detector (PDA) (detection wavelength is 282 nm). The migration of BHT was detected and Irganox 1010 was not detected. Based on the large amount of experimental data, the migration model was fitted by a software, then the migration model of antioxidant BHT was established, the applicability of the two migration model was compared with the actual data. The results showed that the fitting degree ( R2 ) of Weibull model to the actual migration result was greater than 0. 99 and better than Piringer model. It was found that there was a mathematical relationship as τ≈12. 2 ( L2/D) between parameters of Weibull model and Piringer model.