Objective To investigate the clinic-pathological significance of von Willebrand factor (vWF) and P-selectin expression in patients with lupus nephritis (LN).Methods Biopsy specimens from 71patients with LN whose disease course ranged from 2 months to 10 years were examined and scored according to a standardized method.SLE activity was evaluated by the SLE disease activity index (SLEDAI) and the British Isles Lupus Assessment Group index.Immunohistochemistry was used to detect the expressions of vWF and P-selectin in the renal tissue of LN patients and 10 normal controls.Of all the patients,7 had World Health Organization type Ⅱ,10 had type Ⅲ and 36 had WHO type Ⅳ,18 had type Ⅴ lupus nephritis.At the same time,the 24-h urine protein (UP) excretion level,the serum creatinine,the serum C3,C4,album level,antinuclear antibody (ANA),anti-double stranded DNA and disease activity scores of all patients were detected.The relationship of their expressions with the clinicopathological parameters of lupus nephritis was analyzed.ANOVA,Nemenyi test and Pearson's analysis were used for statistical analysis.Results Compared with the control group,the in situ expressions of vWF and P-selectin in the lupus nephritis patients were significantly higher.Among these patients,renal expressions of vWF were higher in type Ⅳ (0.30±0.10) than those with type Ⅱ and Ⅲ (0.12±0.05,0.22±0.14)(x2=9.273,x2=8.712,P＜0.05),while the expressions of P-selectin were higher in type Ⅳ and Ⅴ (0.29±0.05,0.36.±0.10)than those in type Ⅱ and Ⅲ (0.27±0.09,0.29±0.05 )(P＜0.05).Correlation analysis indicated that vWF was correlated significantly with AI and 24-h UP (r=0.403,0.332,P＜0.05 ),while P-selectin was correlated significantly with the scores of activity index (AI),24-h UP excretion rate and SLEDAI (r=0.283,0.453,0.297,P＜0.05 ).The expression of vWF was also closely related to P-selectin expressions (r=0.371,P=0.001).Conclusion These results indicate that vWF and P-selectin play a critical role in the pathogenesis of LN.The detection of these two factors will provide a valuable clinical reference for renal damage.These information provide valuable clues for making better treatment regimen plan and achieving more favorable prognosis.

Objective To investigate the effect of three different routes of administration of analgesic on gastrointestinal function in delivery women with cesarean section.Methods From June 2016 to January 2017,90 delivery women cesarean section were treated in our hospital aged 23-35 years with body mass index (BMI) 25-35 kg/m2,ASA physical status Ⅰ or Ⅱ.Parturients were randomly divided into three groups:intravenous analgesia pump group (group J),skin implanted analgesia pump group (P group) and epidural analgesia pump group (group Y).Group J received postoperative intravenous infusion of sufentanil 5 μg and analgesia pump (3 μg/kg sufentanil+ 100 ml saline)connected with venous channels;group P received postoperative Bipi injection of sufentanil 5 μg introcarplaced in the subcutaneous and connected with analgesia pump (3 μg/kg sufentanil+ 100 ml saline);group Y was given epidural injection of 1％ ropivacaine and 0.5％ lidocaine mixture 4 ml,the analgesia pump (0.15％ ropivacaine+50 μg sufentanil+100 ml saline) was connected with epidural catheter.The recovery time of bowel sounds,the time of firstly anal exhaust,48 hours after surgery,the incidence of nausea,vomiting and bloating were recorded.Results The recovery time of bowel sounds [(14.6±2.3) h] and the time of firstly exhaust time [(20.5±7.9) h] in group Y was significantly earlier than in group J [(18.3±3.6) h and (28.7±8.2) h] and group P [(18.8±4.1) h and (27.9±9.3) h] (P＜0.05).The incidence of nausea (17％),and abdominal distention (20.0％) was significantly lower in group Y than in group J (36.7％ and 47.0％) and group P (33.3％ and 43.0％) (P＜0.05).Conclusion Postoperative analgesia pump of epidural pathway is beneficial to restore the gastrointestinal function on the basis of postoperative analgesia.

Objective To investigate the effect of 17β-estradiol on the pain threshold in neuropathic rats.Methods Fifty fe-male SD rats were divided into five groups by adopting the random number table method,the sham operation group(separating and exposing the left sciatic nerve without ligation and giving the saline injection),the other four groups were established as chronic compression injury(CCI)model of sciatic nerve:CCI group(saline injection),estradiol group(17β-estradiol injection),antagonist group(AP-5 injection)and composite group(17β-estradiol and AP-5 injection),10 cases in each group.The rat mechanical pain threshold value was examined by adopting the paw withdrawal mechanical threshold(PWMT),the rat thermal threshold was exam-ined by adopting the paw withdrawal thermal latency(PWTL),and the expression of NMDAR1 protein was determined by immuno-histochemistry and Western blot.Results Compared with the sham operation group,PWM T in the CCI group and estradiol group was decreased(P<0.05)and PWTL was shortened(P< 0.05),while the expression of NMDAR1 protein was significantly in-creased(P<0.05).Compared with the CCI group,PWMT in the estradiol group was decreased(P<0.05)and PWTL was short-ened(P<0.05),while the expression of NMDAR1 protein was significantly increased(P<0.05).Conclusion 17β-estradiol can de-crease the pain threshold of the neuropathic pain rats by increasing the NMDAR1 expression.

Objective To compare the incidence of metabolic disorders and uric acid (UA) levels between patients with primary aldosteronism (PA) and essential hypertension (EH),and to explore factors associated with UA levels in these patients.Methods A total of 117 PA and 117 EH patients individually matched by sex,age,blood pressure and duration of hypertension were recruited from in-hospital patients who were hospitalized in our department because of suspicion of secondary hypertension from January 2008 to December 2014.Clinical data including metabolic disorders and UA levels were analyzed.Results (1) Body mass index (BMI),waist circumference,plasma triglyceride (TG),low-density lipoprotein cholesterol (LDL-C),free fatty acid (FFA) were significantly higher in EH than in PA group (all P ＜ 0.05).Prevalence of diabetes mellitus or impaired glucose tolerance (DM + IGT) was significantly higher in EH than in PA group (41.9％ (49/117) vs.17.1％ (20/117),P ＜0.01).The prevalence of metabolic syndrome (MS) was also significantly higher in EH than in PA group (51.3 ％ (60/117) vs.24.8％ (29/117),P ＜ 0.01).(2) EH patients had higher homeostasis model assessment for insulin resistance (HOMA-IR) and lower insulin sensitivity index composite (ISI comp) than PA patients,but basic insulin secretion index (HOMA-β) and modified β cell function index (MBCI) were significantly lower in PA than in EH group (P ＜ 0.05).(3) With regard to target organs damages,PA patients revealed higher 24-hour urinary protein,urinary albumin excretion rate (UAER),urinary IgG,urinary α-1 microglobulin,left ventricular mass index and lower urine specific gravity than EH patients (all P ＜ 0.05).There was no significant difference in estimated glomerular filtration rate (eGFR) between two groups (P =0.103).(4) UA level was significantly lower in PA group than in EH group ((314.00 ±89.52) μmol/L vs.(379.16 ± 101.25) μmol/L,P ＜ 0.01).Higher plasma aldosterone concentration and lower plasma renin activity were associated with lower UA level in PA group.Conclusions Compared with sex,age and hypertension duration matched EH patients,PA patients revealed lower UA level and less severe abnormalities of glucose and lipid metabolism,but are associated with severer renal and cardiac damages.The reduced UA level in PA patients is possibly due to the high plasma aldosterone concentration and low plasma renin activity.

Objective:To investigate the arsenic metabolism pattern and possible influencing factors in the population in drinking-water-borne endemic arsenic poisoning (drinking-water-borne arsenic poisoning for short) areas.Methods:In December 2004, a cluster sampling method was used to select arsenic poisoning population (arsenic poisoning group) and healthy population (control group) in drinking-water-borne arsenic poisoning area of Bayannur City, Inner Mongolia Autonomous Region as the survey subjects. A questionnaire survey was conducted. Arsenic content in drinking water at home of survey subjects, the levels of urinary arsenic and its metabolites, including [trivalent arsenic (As Ⅲ), inorganic arsenic (iAs), monomethylarsenic acid (pentavalent, MMA V), dimethylarsenic acid (pentavalent, DMA V), total arsenic (tAs), percentage of inorganic arsenic (iAs%), percentage of monomethylarsenic acid (MMA%), percentage of dimethylarsenic acid (DMA%), primary methylation index (PMI), secondary methylation index (SMI)] were tested using high performance liquid chromatography-inductively coupled plasma mass spectrometry; nail arsenic and nail selenium levels were tested using atomic fluorescence spectrometer. The influencing factors of arsenic metabolism pattern were analyzed by multiple linear regression. Results:A total of 536 survey subjects were included, including 155 individuals in the arsenic poisoning group and 381 in the control group. The water arsenic level ranged from 0.0 to 825.7 μg/L. Compared with the control group, there was no significant difference in the distribution of gender, education level and dental fluorosis in the arsenic poisoning group ( P > 0.05), but there were significant differences in the distribution of age, marital status, smoking, drinking and water arsenic ( P < 0.05). Compared with the control group, the levels of urinary As Ⅲ, iAs, MMA V, DMA V, tAs, MMA%, MMA/DMA and nail arsenic in the arsenic poisoning group were higher ( P < 0.05), while the levels of urinary DMA%, SMI and nail selenium were lower ( P < 0.05); but there was no statistically significant difference in the levels of urinary iAs% and PMI ( P > 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary As Ⅲ (β = - 19.82, - 23.83, 0.61, 0.21, 7.26, 2.98, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary tAs (β = 3.18, 3.25, 1.31, 15.59, P < 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary iAs (β = - 20.47, - 25.90, 0.64, 0.25, 7.87, 3.11, P < 0.05). Age, gender, education level, water arsenic and nail arsenic were the influencing factors of urinary MMA V (β = 0.52, - 17.07, - 21.84, 0.22, 2.77, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary DMA V (β = 2.35, 2.47, 0.85, 9.22, P < 0.05). Conclusions:Compared with healthy individuals, there are differences in arsenic metabolism pattern among individuals with drinking-water-borne arsenic poisoning. Age, gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic may be influencing factors of different arsenic metabolism patterns.

Objective:To investigate the relationship between the outcome of skin injury and urinary arsenic methylation metabolism levels in people exposed to arsenic through drinking water.Methods:Using cluster sampling method, permanent residents from drinking-water-borne endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region were selected as survey subjects in 2004 (before water improvement). In 2017 (after water improvement), 74 survey subjects from 2004 were tracked and followed up. Urine samples were collected from survey subjects and high-performance liquid chromatography inductively coupled plasma mass spectrometry was used to detect the levels of arsenic methylation metabolites in urine. According to the "Diagnosis of Endemic Arsenic Poisoning" (WS/T 211-2015), the clinical grading (normal, suspicious, mild, moderate and severe) of skin injury of the survey subjects and the outcome of 2017 (improved, unchanged, aggravated) were assessed. A database was established and SPSS 25.0 software was used for statistical analysis.Results:The clinical grading ratios of skin injuries among survey subjects in 2004 and 2017 were compared, the differences were statistically significant (normal, suspicious, mild, moderate and severe: 38, 18, 4, 14 cases in 2004 and 27, 31, 3, 13 cases in 2017, χ 2 = 53.02, P < 0.001). Compared with 2004, in 2017, the levels of total arsenic (tAs), inorganic arsenic (iAs), monomethylarsenic (MMA), dimethylarsenic (DMA), percentage of inorganic arsenic (iAs%), and ratio of monomethylarsenic to dimethylarsenic (MMA/DMA) in the urine of survey subjects were low, and the differences were statistically significant ( Z = - 8.24, - 9.07, - 7.81, - 8.04, - 8.24, - 3.56, P < 0.001). The levels of dimethylarsenic percentage (DMA%), monomethylation rate (PMI) and dimethylation rate (SMI) were higher, and the differences were statistically significant ( Z = - 6.39, - 8.24, - 3.52, P < 0.001). In 2004, patients with different clinical grading of skin injuries had different outcomes in 2017 (χ 2 = 30.80, P < 0.001). There were statistically significant differences in tAs, iAs, MMA and DMA variation in urine among skin injury patients with different outcomes ( H = 10.62, 9.35, 8.80, 9.13, P < 0.05). Conclusions:Improving water can significantly reduce the levels of tAs, iAs, MMA, and DMA in the urine of arsenic exposed individuals. The outcome of skin injury in individuals exposed to arsenic through drinking water is related to the variation of urinary arsenic methylation metabolites tAs, iAs, MMA, and DMA.

Objective: To describe the current reporting of pneumonia of unknown etiology (PUE) and factors that affect reporting by clinicians in China using the PUE surveillance system in order to provide a reference for improving PUE reporting rates in the future. Methods: Clinicians were recruited via the Sojump platform and requested to complete an anonymous self-administered questionnaire. Multivariate logistic regression analysis was used to assess factors influencing clinicians' reporting activities. Results: This study showed a low PUE case reporting rate and a poor understanding of PUE reporting among the investigated clinicians. Of the 136 clinicians who had diagnosed PUE cases, multivariate logistic regression analysis results showed that clinicians who had attended in-hospital training were more likely to report PUE than those who had not (OR 4.48, 95% CI 1.49-13.46). Clinicians with an expert panel on PUE in their hospital were more likely to report PUE cases than those without (OR 5.46, 95% CI 1.85-16.11). Conclusions: There is a need to promote and reinforce PUE surveillance system training among medical staff. In addition, PUE testing technologies in hospital laboratories should be upgraded, especially in primary and unclassified hospitals, to increase surveillance efficiency and improve PUE reporting rates.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*