The mechanism of proprotein convertase subtilisin/kexin type 9 in the inflammatory response induced by Helicobacter pylori infection / 中华消化杂志

Objective:To explore the mechanism of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the inflammatory response induced by Helicobacter pylori ( H. pylori) infection. Methods:From May 1, 2020 to January 31, 2021, 60 patients with gastritis (30 H. pylori positive and 30 H. pylori negative)and 30 healthy individuals, who initially visited the Department of Gastroenterology, Shiyan Taihe Hospital were collected, and their serum PCSK9 levels were detected. Normal gastric epithelial cell line GES-1 and macrophages induced from THP-1 cells, and GES-1 infected with H. pylori were selected to prepare different supernatant media. Phosphate buffer saline empty medium (negative control group), normal GES-1 cell supernatant medium ( H. pylori-uninfected GES-1 group), H. pylori infected GES-1 cell supernatant medium ( H. pylori infected GES-1 group), H. pylori infected GES-1 cell supernatant + PCSK9 neutralizing antibody medium (anti PCSK9 group), H. pylori infected GES-1 cell supernatant+ human immunoglobulin G medium (isotype control group) were established. The differences between H. pylori infected GES-1 group and H. pylori-uninfected GES-1 group, negative control group, anti PCSK9 group and isotype control group in number of migrated macrophages, relative expression level of CC chemokine receptor ( CCR2), the levels of released interleukin(IL)-6 and cell necrosis factor (TNF)- α, level of CD8 + T cell membrane phosphorylation, and the number of macrophage colonies were determined by Transwell assay, real time fluorescence quantitative polymerase chain reaction, plate colony assay, H. pylori and phagocytosis lysosome co-localization assay. The regulating mechanism of PCSK9 in H. pylori infection induced inflammation was analyzed. Independent sample t test was used for statistical analysis. Results:The serum level of PCSK9 of patients with H. pylori positive gastritis was higher than that of patients with H. pylori negative gastritis and healthy individuals ((384.00±57.57) g/L vs. (208.80±48.89) and (176.10±47.14) g/L), and the differences were statistically significant ( t=12.71 and 15.31; both P<0.001). Compared with negative control group, H. pylori standard strain and 4 isolated H. pylori strains could stimulate GES-1 to secrete PCSK9 ((1 267.00±287.50) g/L vs.(2 717.00±199.20), (4 858.00±302.40), (3 167.00±334.20), (6 075.00±597.30), (4 283.00±331.20) g/L), and the differences were statistically significant( t=10.15, 21.09, 10.56, 17.77, 16.85, all P<0.001). The number of migrated macrophages, CCR2 mRNA expression level in macrophage, expression levels of IL-6 and TNF-α, and the number of macrophage colonies of H. pylori-infected GES-1 group were all higher than those of H. pylori-uninfected GES-1 group and negative control group (132.20±5.67 vs.84.83±4.62, 39.83±4.12; 8.66±0.94 vs. 6.52±0.47 and 1.00±0.09, (281.00±8.56) ng/L vs. (115.00±7.72) and (64.00±5.44) ng/L, (619.80±18.47) ng/L vs.(373.30±12.85)and (225.70±6.44) ng/L, (357.00±16.31) colony forming unit (CFU) vs. (134.80±8.64) and (74.17±9.68) CFU), and the differences were statistically significant ( t=15.85, 32.27; 4.96, 19.79; 35.28, 52.43; 26.84, 49.37; 29.49, 36.53; all P<0.001). The percentage of co-localization of H. pylori and phagocytosis lysosome, and the expression of cell membrane CD3ζ Tyr142, granzyme B and perforin in CD8 + T cell of H. pylori-infected GES-1 group were lower than that of H. pylori-uninfected GES-1 group ((15.33±1.86)% vs. (34.50±3.72)% and (65.67±3.56)%, 464.20±120.80 vs. 1 924.00±262.10 and 2 390.00±484.10; (6.41±0.42)% vs.(17.37±0.73)% and (26.60±1.57)%; (6.84±1.37)% vs.(14.53±0.48)% and (26.22±1.21)%), and the differences were statistically significant( t=11.27 and 30.70, 12.39 and 9.45, 30.50 and 31.90, 25.96 and 13.00; all P<0.001). The number of migrated macrophages, the relative expression level of CCR2 mRNA, the expression levels of IL-6 and TNF-α, and the number of macrophage colonies of anti-PCSK9 group were all lower than those of isotype control group (72.50±4.97 vs. 128.30±6.74, 0.82±0.06 vs. 1.00±0.08, (85.50±4.37) ng/L vs. (277.70±8.98) ng/L, (291.80±13.69) ng/L vs. (615.30±12.65) ng/L, (111.50±10.21) CFU vs. (346.20±18.04) CFU), and the differences were statistically significant ( t=16.33, 4.40, 47.13, 42.50 and 27.73, all P<0.001). The percentage of co-localization of H. pylori and phagocytosis lysosome, the expression levels of CD3ζ Tyr142, granzyme B and perforin of anti-PCSK9 group were all higher than those of isotype control group ((51.05±3.03)% vs. (16.71±1.91)%, 2 948.00±384.00 vs. 1 156.00±178.60, (53.88±3.86)% vs. (5.88±0.93)%, (32.80±2.07)% vs. (6.83±0.54)%), and the differences were statistically significant ( t=23.49, 10.36, 29.60 and 29.76, all P<0.001). Conclusions:H. pylori can inhibit CD8 + T activation and cytotoxicity by inducing the release of PCSK9 from gastric epithelial cells, and can also recruit macrophages, activate nuclear factor-κB signal axis to up-regulate the level of released inflammatory factors from macrophages, inhibit the phagocytosis and killing effects of macrophages, so as to regulate the inflammatory response.

Effects of treatment based on different target mean arterial pressure on gastrointestinal function in septic shock patients with hypertension / 中华危重病急救医学

Objective:To investigate the effect of fluid resuscitation and circulatory support, directed by different target mean arterial pressure (MAP), on abdominal blood flow, gastrointestinal function and inflammatory response in septic shock patients with hypertension.Methods:A prospective randomized controlled study was conducted. Hypertensive patients with septic shock admitted to the department of intensive care unit (ICU) of Liuzhou People's Hospital from January 1, 2019 to May 31, 2020 were enrolled. Patients were randomly divided into the low MAP groups (low standard group, LS group) or high MAP group (high standard group, HS group). According to the Surviving Sepsis Campaign Guidelines in 2016 and the updated guideline in 2018, all patients were given treatment of primary disease, fluid resuscitation, supportive management. The target MAP was 65-70 mmHg (1 mmHg = 0.133 kPa) in LS group, and was 75-80 mmHg in HS group. Acute gastrointestinal function injury (AGI) classification was performed on the 1st, 3rd and 7th day. The mean flow rate (Vm) and resistance index (RI) of superior mesenteric artery were evaluated using ultrasound, and the gastrointestinal function was dynamically evaluated using the modified single section ultrasonic gastric antrum method. The gastric antrum movement index (MI) and gastric empaging time (GET) were recorded. The levels of inflammatory markers in serum were detected by enzyme linked immunosorbent assay (ELISA), such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), procalcitonin (PCT) and vascular endothelial growth factor (VEGF). The target MAP, the days of use of vasopressors and the amount of fluid resuscitation were recorded.Results:A total of 208 hypertensive patients with septic shock were enrolled, including 109 in the LS group and 99 in the HS group. There were no significant differences in gender, age, acute physiology and chronic health evaluationⅡ (APACHEⅡ) score and sequential organ failure assessment (SOFA) score between the two groups when diagnosed. After treatment, there was no significant difference in AGI classification between the LS group and HS group on the 1st day. On the 3rd and 7th day, there were statistical differences between the two groups (3rd day: proportion of Ⅰ, Ⅱ, Ⅲ, Ⅳ grades were 25.69%, 56.88%, 11.93%, 5.50% in LS group, 15.15%, 54.55%, 25.25%, 5.05% in HS group, respectively, χ 2 = 7.900, P = 0.048; 7rd day: proportion of Ⅰ, Ⅱ, Ⅲ, Ⅳ grades were 44.96%, 49.54%, 3.67%, 1.83% in LS group, 31.31%, 52.53%, 11.11%, 5.05% in HS group, respectively, χ 2 = 8.178, P = 0.042). The Vm of superior mesenteric artery was higher and the RI was lower in the LS group than those in the HS group on day 1, 3 and 7 [Vm (cm/s): 21.72±3.02 vs. 19.50±2.83, 20.42±2.62 vs. 17.02±1.99, 26.52±2.70 vs. 22.47±4.03; RI: 0.86±0.05 vs. 0.92±0.04, 0.87±0.05 vs. 0.95±0.05, 0.81±0.03 vs. 0.85±0.03, all P < 0.01]. The MI was higher and the GET was shorter in the LS group than those in the HS group on day 3 and day 7 [MI: 3.00±0.33 vs. 2.60±0.29, 4.50±0.51 vs. 3.90±0.33; GET (minutes): 86.01±19.78 vs. 100.99±25.01, 71.00±16.37 vs. 84.98±20.18, all P < 0.01]. In addition, the levels of serum TNF-α, IL-6, PCT, VEGF were lower in the LS group than those in the HS group after 3 days of treatment [TNF-α (ng/L): 147.05±28.32 vs. 256.99±27.04, IL-6 (ng/L): 762.99±57.83 vs. 1 112.30±118.32, PCT (μg/L): 37.00±5.58 vs. 56.00±12.36, VEGF (ng/L): 123.00±19.78 vs. 167.01±21.55, all P < 0.05]. The target MAP was maintained at (68.02±4.71) mmHg in LS group, and (79.04±3.04) mmHg in HS group. The difference between the two groups was statistically significant ( P < 0.01). Compared with the HS group, the days of using vasopressors was shorter in LS group (days: 3.50±1.27 vs. 4.55±1.47), and the amountof fluid was reduced significantly (mL: 1 602.29±275.49 vs. 2 000.30±272.59, both P < 0.01). Conclusion:Maintaining a low target mean arterial pressure (65-70 mmHg) in hypertensive patients with septic shock can improve blood supply of superior mesenteric artery, protect the gastrointestinal function, reduce the level of inflammatory factors, and diminish the duration of using vasopressors and the amount of fluid.

Treatment of hypertensive basal ganglia cerebral hemorrhage with different surgical approaches / 中华全科医师杂志

According to the locations of main hematomas,60 patients with hypertensive basal ganglia hemorrhage were surgically treated through different approaches from June 2014 to September 2017.Thirty six cases with anterior hematoma near the Sylvian point were treated through transsylvian-transinsular approach,24 cases with the posterior hematoma far from the Sylvian point were treated through translower-rolandic-point (transLRP) transinsular approach (n =11) or transsuperior-temporal-sulcus (transSTS) transinsular approach (n =13),respectively.All patients were followed up for at least 6 months and evaluated by Glasgow Outcome Scale.Fourteen patients showed good recovery,25 patients showed moderate disability,18 patients showed severe disability,one patients showed vegetative survival and two patients died.

Comparison of the effects of two different methods of craniotomy in the treatment of elderly patients with hypertensive striatocapsular hemorrhage / 中国基层医药

Objective To compare the clinical effect of the small bone flap craniotomy and traditional craniotomy in the treatment of elderly patients with hypertensive striatocapsular hemorrhage .Methods According to the digital table ,80 patients with hypertensive striatocapsular hemorrhage were randomly divided into control group and treatment group ,40 cases in each group .The treatment group was treated with small bone flap craniotomy ,and the control group was treated with traditional craniotomy .The operative incision length ,intraoperative blood loss ,operation time,hematoma clearance rate,rebleeding rate,GCS score,postoperative pulmonary infection rate and GOS score in the 1 month after treatment were compared between the two groups .Results The operative incision length , intraoperative blood loss, operative time, GCS score after 1 week, pulmonary infection of the treatment group were (7.0 ±1.5)cm,(100 ±35)mL,(1.5 ±0.6)h,(12.5 ±1.4),25.0％,respectively,which of the control group were (18.0 ±4.5)cm,(500 ±85) mL,(2.2 ±0.8) h,(10.5 ±1.1),47.5％,respectively,the differences between the two groups were statistically significant (t=303.791,P=0.000;t=244.467,P=0.000;t=24.366,P=0.003;t=3.294,P=0.031;χ2 =4.381,P=0.036).The hematoma clearance rate,rebleeding rate of the treatment group were 90.0％,7.5％,respectively,which of the control group were 85.0％,10.0％,respectively,there were no statistically significant differences between the two groups (χ2 =0.457,P=0.499;χ2 =0.157,P=1.692).The prognosis of the patients in the treatment group was significantly better than those in the control group (Z=-2.022,P=0.043). Conclusion The small bone flap craniotomy in the treatment of hypertensive striatocapsular hemorrhage has the advantages of less trauma , shorter operative time , less intraoperative bleeding , high hematoma clearance rate , low rebleeding rate,low complication rate and good prognosis .

Co-stimulating molecule B7-H3 and tumors / 国际肿瘤学杂志

B7-H3,a newly discovered co-stimulatory regulatory protein member of the B7 family.Its mRNA is ubiquitously expressed in a wide spectrum of tissues.As a co-stimulatory or co-inhibitory signal molecule which can regulate immune response,B7-H3 plays an important role in the immune system.Besides,B7-H3 can be also involved in cancer progression via non-immunological.Recently,the aberrant expression of B7-H3 has been described in various malignancies,and significantly correlated with poor prognosis and cancer progression.Therefore,B7-H3 is considered as an early diagnostic and prognostic marker and therapeutic target for tumors,but the specific molecular mechanisms of B7-H3 regulation are poorly understood.The immune and gene therapy of tumor by target B7-H3 has made some progress.

Survey on needs of main caregivers of children with cerebral palsy / 现代临床护理

Objective To investigate the needs of the main caregivers of children with cerebral palsy and probe into the nursing strategies. Method One hundred and fifteen main caregivers of children with cerebral palsy participated in the survey by a general state questionnaire and the family needs questionnaire. Results The score by the family needs questionnaire was (96.13 ± 19.47), with an average score of (3.00 ± 0.61). And the top needs of the main caregivers were information and econony need. Conclusions The needs of the main caregivers of children with cerebral palsy are high. More attention should be paid to community and family-based rehabilitation and supports to those care-givers.

Polymorphisms of intercellular adhesion molecule-1 gene K469E and platelet endothelial cell adhesion molecule-1 gene C373G in patients with preeclampsia / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the distributions of genotypic and allelic frequencies of intercellular adhesion molecule-1 (ICAM-1) gene K469E and platelet endothelial cell adhesion molecule-1 (PECAM-1) gene C373G in patients with preeclampsia.</p><p><b>METHODS</b>Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and DNA sequencing were used for detecting ICAM-1 gene K469E and PECAM-1 gene C373G genotypes in 110 women with preeclampsia and 110 normotensive pregnant women in comparison with their clinical characteristics.</p><p><b>ESULTS</b>The distributions of observed and expected genotype frequencies were consistent with Hardy-Weinberg equilibrium. No significant differences were found in the genotype and allele frequencies of ICAM-1 gene K469E between the two groups (P>0.05), but the CC and the CG genotype frequencies of PECAM-1 gene C373G were significantly different between them (P<0.05). The relative risk for preeclampsia of CG genotype was 1.959 folds of that in CC genotype carriers (OR=1.959, 95%CI: 1.090-3.520, P=0.024), and this association still existed after adjustment for age, gravidity, parity and BMI in logistic regression models. The C373G allele frequencies showed no significant difference between the two groups (P>0.05).</p><p><b>CONCLUSIONS</b>The CG genotype of PECAM-1 gene C373G genetically predispose the carriers to preeclampsia, while ICAM-1gene K469E polymorphisms is not associated with preeclampsia.</p>

Proliferation and differentiation of rat bone marrow mesenchymal stem cells under different mechanical strains / 中国组织工程研究

BACKGROUND:In vitro and in vivo studies of cel response to a variety of mechanical loadings have demonstrated the stimulation of bone formation by loads. However, the effects of different mechanical strains on the same cel s have never been adequately studied by far. OBJECTIVE:To investigate the effects of different mechanical strains on rat bone marrow mesenchymal stem cel s. METHODS:Rat bone marrow mesenchymal stem cel s were isolated and cultured in vitro. Bone marrow mesenchymal stem cel s were subjected to different stimulations including dynamic stretch, static stretch and hybrid stretch through the use of custom-made mechanical stretch device. Cel ular proliferation, alkaline phosphatase activity and mRNA expression of Runx2 of bone marrow mesenchymal stem cel s were detected and the secretion of osteocalcin was evaluated under three different stretch modes respectively. RESULTS AND CONCLUSION:Compared to the control group, cel proliferation increased by 18.67%, however, alkaline phosphatase activity, Runx2 expression and osteocalcin secretion were not changed obviously in the static stretchgroup. Compared to the control group, alkaline phosphatase activity, Runx2 expression and osteocalcin secretion increased by 60.33%, 49.67%and 48%respectively;however, cel proliferation was inhibited, in the dynamic stretch group. Compared to the control group, cel proliferation was slightly, but not significantly, increased in the hybrid stretch group, and the alkaline phosphatase activity, Runx2 expression and osteocalcin secretion increased although the increases were not as apparent as those in the dynamic stretch group. These findings suggest that static mechanical strain can significantly promote cel proliferation, the dynamic mechanical strain more greatly promotes osteogenic differentiation of bone marrow mesenchymal stem cel s, and the hybrid mechanical strain promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cel s.

The influence and safety of denosumab on bone mineral density of lumbar spine in women with low bone mass: a meta-analysis / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the influence and safety of denosumab on bone mineral density (BMD) of lumbar spine in women with low bone mass.</p><p><b>METHODS</b>The clinical literatures concerning denosumab for the treatment of osteopenia or osteoporosis in women were searched from Medline, Embase, Cochrane Central Register of Controlled Trials, Wanfang database, China National Knowledge Infrastructure database, Chinese Biomedical Database. Randomized controlled trials (RCT) were selected by the inclusive and exclusive criteria. The jadad scale was used in the quality assessment of included studies. Meta-analysis of valid data picked from included studies was performed by RevMan 5.0.24 software.</p><p><b>RESULTS</b>5 RCT were included in this meta-analysis. The results of meta-analysis using the fixed effects model showed that, the increase level of lumbar BMD after 12 month was 5.45% (95% CI, 5.05%~5.84%) higher in denosumab group than in placebo control group (P<0.00001). The serious adverse event, serious infection event and pack pain occurred during the followed-up were analysed using fixed effects model. The results showed no significant difference between two groups.</p><p><b>CONCLUSION</b>Compared with placebo control group, denosumab can significant increase the BMD of lumbar spine, and the safety of two groups is similar.</p>

Study on current staffmg of nurses and need of hospital nursing human resources in China / 中国实用护理杂志

Objective To investigate the current staffing of nurses and need of hospital nursing human resources in China.Methods Data were collected from 181 secondary and tertiary hospitals and 9774 nurses in mainland China by questionnaires.Results The average doctor-nurse ratio was 1 ∶ 1.39 in tertiary hospitals and 1 ∶ 1.31 in secondary hospitals.The doctor-nurse ratios in 164 hospitals (97.6％) and the proportion of nurses in health care staff in 105 hospitals (61.8％) had not reached the standard set by the Ministry of Health of China.62.3％ nurses held secondary diploma for their initial nursing education.The constituent ratio of nurses held secondary diploma decreased,while the ratio of nurses held advanced diploma and bachelor degree increased in the last 5 years from 2003 to 2007.Sixty percent of newly employed nurses were contract nurses in 2003.The proportion increased to 78％ in 2007,and in some regions it accounted for more than 90％ of new nurses.The needs and constituent ratio of nurses with.secondary diploma and advanced diploma would decrease while nurses with bachelor degree and master degree would increase in the next 5 years (from 2009 to 2013).Conclusions The nursing shortage is still severe in China,and nursing staff mainly held secondary diploma for their initial nursing education.Most of new nurses were employed as conwact nurses.The need of hospitals for nurses has increased,especially for nurses with higher educational level such as bachelor degree and master degree,while the need for secondary diploma hold ers have decreased.The need for advanced diploma holders has increased in the last 5 years and would decrease in the next 5 years,but they would still be the majority of employed nurses.The authors suggested that the staffing of nursing manpower,the work environments and career development of contract nurses should be improved,and the initial nursing education should be upgraded to meet the needs of hospitals.