Objective:To compare the infection status of severe fever with thrombocytopenia syndrome (SFTS) between the non-endemic area (Yixian county, Huangshan city) and the endemic area (Qianshan city, Anqing city) in Anhui province, and to explore the possibility of Yixian county being a natural focus of SFTS, thereby providing a scientific basis for the formulation of prevention and control strategies.Methods:In Xidi town, Yixian county, and Shuihou town, Qianshan city, one administrative village with the highest number of reported cases in the past three years was selected as the study village in each area, along with one control village with no reported cases. The study investigated the total antibody positivity rates of SFTS virus (SFTSV) in natural populations and host animals, as well as the density and virus-carrying rate of the vector ticks. Differences in total antibody positivity rates between the two regions were compared.Results:The total SFTSV antibody positivity rates in the natural population and host animals in the surveyed villages (control villages) of Qianshan city and Yi county were 8.7% and 8.0% (3.3%, 4.1%) and 0.0%, 9.1% (50.0%, 66.7%), respectively. There was no statistically significant difference in the infection rates of the natural population and host animals between the surveyed villages (control villages) in different endemic regions (all P>0.05). In the surveyed villages of Qianshan city and Yi county, the free-living tick densities were 1.4 ticks/hour per flag and 1.7 ticks/hour per flag, respectively; the parasitic tick densities were 0.4 ticks/host and 2.5 ticks/host, respectively; the tick infestation rates were 33.3% and 35.3%, respectively; and the tick density indices were 1.3 ticks/host and 7.2 ticks/host, respectively. Conclusions:The natural populations and host animals in some areas of Yixian county exhibit high SFTSV infection rates, and the tick density is also high, suggesting that the region may have become a natural focus of SFTS. Therefore, it is necessary to further strengthen capabilities in surveillance, diagnosis, and clinical treatment to address the potential risk of SFTS outbreaks.

Objective:To compare the infection status of severe fever with thrombocytopenia syndrome (SFTS) between the non-endemic area (Yixian county, Huangshan city) and the endemic area (Qianshan city, Anqing city) in Anhui province, and to explore the possibility of Yixian county being a natural focus of SFTS, thereby providing a scientific basis for the formulation of prevention and control strategies.Methods:In Xidi town, Yixian county, and Shuihou town, Qianshan city, one administrative village with the highest number of reported cases in the past three years was selected as the study village in each area, along with one control village with no reported cases. The study investigated the total antibody positivity rates of SFTS virus (SFTSV) in natural populations and host animals, as well as the density and virus-carrying rate of the vector ticks. Differences in total antibody positivity rates between the two regions were compared.Results:The total SFTSV antibody positivity rates in the natural population and host animals in the surveyed villages (control villages) of Qianshan city and Yi county were 8.7% and 8.0% (3.3%, 4.1%) and 0.0%, 9.1% (50.0%, 66.7%), respectively. There was no statistically significant difference in the infection rates of the natural population and host animals between the surveyed villages (control villages) in different endemic regions (all P>0.05). In the surveyed villages of Qianshan city and Yi county, the free-living tick densities were 1.4 ticks/hour per flag and 1.7 ticks/hour per flag, respectively; the parasitic tick densities were 0.4 ticks/host and 2.5 ticks/host, respectively; the tick infestation rates were 33.3% and 35.3%, respectively; and the tick density indices were 1.3 ticks/host and 7.2 ticks/host, respectively. Conclusions:The natural populations and host animals in some areas of Yixian county exhibit high SFTSV infection rates, and the tick density is also high, suggesting that the region may have become a natural focus of SFTS. Therefore, it is necessary to further strengthen capabilities in surveillance, diagnosis, and clinical treatment to address the potential risk of SFTS outbreaks.

BACKGROUND/OBJECTIVES: The study examined the association between homocysteine and diabetes mellitus in patients with H-type hypertension and assessed the possible effect modifiers. SUBJECTS/METHODS: This cross-sectional study included 1,255 eligible participants in the ‘H-type Hypertension Management and Stroke Prevention Strategic International Science and Technology Innovation Cooperation Project’ among rural Chinese people with H-type hypertension. A multivariate logistic regression model was used to evaluate the relationship between homocysteine and diabetes mellitus. RESULTS: The mean level of total homocysteine (tHcy) in the diabetes mellitus population was 19.37 μmol/L, which was significantly higher than the non-diabetic patients (18.18 μmol/L). When tHcy was analyzed as a continuous variable, the odds ratio (OR) of diabetes was 1.17 (95% confidence interval [CI], 1.01–1.35; per interquartile range). When tHcy was stratified according to the quintile, the ORs for diabetes were 2.86 (95% CI, 1.22–6.69) in the highest quintile (tHcy ≥ 20.60 μmol/L) compared to the reference group (tHcy < 12.04 μmol/L). When tHcy was grouped by 15 μmol/L and 20 μmol/L, patients with tHcy ≥ 20 μmol/L had a significantly (P = 0.037) higher risk of diabetes (OR, 2.03; 95% CI, 1.04–3.96) than in those with tHcy < 15 μmol/L. Subgroup analysis showed that the tHcy-diabetes association was unaffected by other variables. CONCLUSION In this study of rural Chinese people with H-type hypertension, the tHcy levels showed a positive association with diabetes mellitus. This independent association is unaffected by other potential risk factors.

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*

OBJECTIVE To study the improvement effects of Cannabis sativa oil on the symptoms in dextran sodium sulfate （DSS）-induced ulcerative colitis （UC） model rats， and to investigate its effects on intestinal flora of rats. METHODS Forty SD rats were randomly divided into control group， model group， C. sativa oil group （1 g/kg） and sulfasalazine group （positive control， 300 mg/kg）， with 10 rats in each group. The rats in control group and model group were given 0.5% polysorbate 80 by gavage， and the rats in C. sativa oil group and sulfasalazine group were given corresponding drug solution by gavage once a day for 10 days. From the 4th day， rats in model group， C. sativa oil group and sulfasalazine group were given 4% DSS solution for 7 consecutive days to establish UC model. The body weight， disease activity index （DAI） score， colon length， colon weight， weight per unit length of colon， the pathological changes of colon tissue， and the contents of tumour necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in serum of rats were determined. The changes of intestinal flora in rats were detected by high- throughput sequencing. RESULTS Compared with control group， the body weight and the length of colon were decreased significantly in model group， while DAI score， the weight of colon， weight per unit length of colon， serum contents of TNF-α and IL-6 were increased significantly， and the content of IL-10 was decreased significantly （P＜0.05）； epithelial layer of colon tissue fell off， inflammatory cells infiltrated and invaded the submucosa， and intestinal glands were disordered. Compared with model group， above indexes of C. sativa oil group and sulfasalazine group were reversed significantly （P＜0.05）， and related symptoms were improved significantly. The result of flora sequencing showed that ACE index and Chao1 index of model group were decreased significantly， compared with control group （P＜0.05）； while Chao1 index of C. sativa oil group was increased significantly， compared with model group （P＜0.05）. Compared with control group， 41 genera of bacteria in the model group changed； compared with model group， C. sativa oil could return 3 of the 41 genera to normal state， including Dubosilla， Porphyrobacter and Allobaculum. CONCLUSIONS C. sativa oil can improve the symptoms of UC model rats by regulating the diversity of intestinal flora， increasing beneficial bacteria and decreasing pathogenic bacteria.

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

Objective:Assess the relationship between elevated antiphospholipid antibodies and thrombosis in hospitalized patients.Methods:Case control study. A total of 385 patients (149 males and 236 females, aged from 1 to 105 years, with a median age of 37 years) who were hospitalized in Peking University First Hospital from January 2015 to December 2019 and tested positive for any one of the anti-phospholipid antibodies were included in the study. All subjects were divided into thrombotic group and non-thrombotic group according to whether thrombus was detected by imaging examination during hospitalization. In thrombosis group, there were 66 males and 36 females, aged from 3 to 105 years, with a median age of 58 years. In non-thrombosis group, there were 83 males and 200 females, aged from 1 to 94 years, with a median age of 31 years. Clinical data and laboratory data of patients were recorded. ACL-IgM/IgG and anti-β2GPI-IgM/IgG were detected by ELISA and LA was detected by dRVVT and SCT on automatic coagulation analyzer. The rates of age, gender, smoking, obesity, hypertension, hyperlipidemia, diabetes and the median level of antiphospholipid antibodies were compared between two groups. Logistic multivariate regression analysis was used to determine the risk factors for thrombotic events. The mid-to-high titer value of aCL was established by the χ 2-trend test and verified by logistic regression. Results:The median age (58 years) and the rates of male (64.7%), smoking (16.7%), hypertension (63.7%) and diabetes (28.4%) in thrombus group were significantly higher than those in non-thrombus group ( Z=7.685, χ2=38.077, 16.312, 37.769, 24.749 respectively; P<0.01). The positive rate of anti-β2GPI-IgG and dRVVT in thrombosis group (11.8% and 78.4%) was significantly higher than that in non-thrombosis group (5.3% and 60.1%), as well as the median level of dRVVT (1.29 RU/ml vs 1.23 RU/ml) (χ2=3.864 and 10.309, Z=3.539; P<0.05). The median level of aCL-IgM was higher in non-thrombosis group (2.3 MPL vs 2.0 MPL). The positive rate of aCL-IgG was slightly higher in thrombosis group (18.6% vs 10.6%). Logistic regression analysis showed that men, hypertension, diabetes, advanced age, elevated dRVVT, and elevated anti-β2GPI-IgG are risk factors for thrombosis. Taking 36 GPL as the medium-to-high titer value of aCL-IgG, the risk of thrombosis increased by 2.45 times. Conclusions:In the anti-phospholipid antibody profile, LA detected by dRVVT method, anti-β2GPI-IgG and aCL-IgG may be valuable laboratory indicators for inpatient thrombotic events. The mid-to-high titer value of aCL-IgG is set at 36 GPL to distinguish the risk of thrombosis.

Objective:To explore the clinical application of robot-assisted laparoscopic single-position nephroureterectomy and bladder sleeve resection for upper urinary tract urothelial carcinoma (UTUC).Methods:The clinicopathological data of 15 UTUC patients admitted to Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from October 2018 to May 2020 were retrospectively analyzed. There were 8 males and 7 females, with a median age of 58.6 (ranging 52.6-69.6) years, including 8 cases of renal pelvic cancer, 2 cases of upper ureteral cancer, 5 cases of middle and lower ureteral cancer.The tumor located on the left side in 5 cases and right side in 10 cases. All 15 patients underwent robot-assisted one-step transperitoneal nephroureterectomy and bladder sleeve resection by the same surgeon. The patients were placed in a 70° healthy side lying position with a 10° head lower and foot high position. After routinely dissecting the kidneys and controlling the renal hilum, we continued to dissect the ureter down to the orifice of the bladder. The lymph node dissection was performed when dissecting the kidney and ureter. Then the ureter was resected like a sleeve and the bladder was sutured. Observation indicators, such as operation time, blood loss, postoperative drainage tube and urinary catheter placement days, were recorded.Results:All 15 patients were successfully completed the operation in the same position and the same robot berth without conversion. The median operation time was 103 (ranging 82-185) min, and the intraoperative median blood loss was 60 (ranging 30-120) ml. The postoperative median drainage catheter placement time was 3 (ranging 2-5) d, the postoperative median hospital stay was 5 (ranging 4-7) d, and the postoperative urinary catheters were placed for 14 days. Postoperative pathological examinations of 15 patients showed UTUC without positive margins. The median follow-up time was 15 (ranging 10-30) months. All 15 patients survived. One patient was found a recurrence in the bladder after cystoscopy. There was no tumor progression after bladder tumor resection and bladder perfusion chemotherapy, and no tumor recurrence or metastasis was seen in the remaining 14 cases.Conclusions:Robot-assisted single-position transperitoneal nephroureterectomy for UTUC does not need to change patient position and robot berth, which effectively shortens the operation time, and achieves good tumor control effect. The short-term follow-up results were satisfactory.

Objective:Assess the relationship between elevated antiphospholipid antibodies and thrombosis in hospitalized patients.Methods:Case control study. A total of 385 patients (149 males and 236 females, aged from 1 to 105 years, with a median age of 37 years) who were hospitalized in Peking University First Hospital from January 2015 to December 2019 and tested positive for any one of the anti-phospholipid antibodies were included in the study. All subjects were divided into thrombotic group and non-thrombotic group according to whether thrombus was detected by imaging examination during hospitalization. In thrombosis group, there were 66 males and 36 females, aged from 3 to 105 years, with a median age of 58 years. In non-thrombosis group, there were 83 males and 200 females, aged from 1 to 94 years, with a median age of 31 years. Clinical data and laboratory data of patients were recorded. ACL-IgM/IgG and anti-β2GPI-IgM/IgG were detected by ELISA and LA was detected by dRVVT and SCT on automatic coagulation analyzer. The rates of age, gender, smoking, obesity, hypertension, hyperlipidemia, diabetes and the median level of antiphospholipid antibodies were compared between two groups. Logistic multivariate regression analysis was used to determine the risk factors for thrombotic events. The mid-to-high titer value of aCL was established by the χ 2-trend test and verified by logistic regression. Results:The median age (58 years) and the rates of male (64.7%), smoking (16.7%), hypertension (63.7%) and diabetes (28.4%) in thrombus group were significantly higher than those in non-thrombus group ( Z=7.685, χ2=38.077, 16.312, 37.769, 24.749 respectively; P<0.01). The positive rate of anti-β2GPI-IgG and dRVVT in thrombosis group (11.8% and 78.4%) was significantly higher than that in non-thrombosis group (5.3% and 60.1%), as well as the median level of dRVVT (1.29 RU/ml vs 1.23 RU/ml) (χ2=3.864 and 10.309, Z=3.539; P<0.05). The median level of aCL-IgM was higher in non-thrombosis group (2.3 MPL vs 2.0 MPL). The positive rate of aCL-IgG was slightly higher in thrombosis group (18.6% vs 10.6%). Logistic regression analysis showed that men, hypertension, diabetes, advanced age, elevated dRVVT, and elevated anti-β2GPI-IgG are risk factors for thrombosis. Taking 36 GPL as the medium-to-high titer value of aCL-IgG, the risk of thrombosis increased by 2.45 times. Conclusions:In the anti-phospholipid antibody profile, LA detected by dRVVT method, anti-β2GPI-IgG and aCL-IgG may be valuable laboratory indicators for inpatient thrombotic events. The mid-to-high titer value of aCL-IgG is set at 36 GPL to distinguish the risk of thrombosis.

Objective To examine the effects of oxidative stress induced damage to the Prestin expression in HEI-OC1 cells,and to study the mechanism of sensory deafness.Methods We used different concentrations (50μM,100μM,200μM)of hydrogen peroxide canister to cultivate HEI-OC1 cells,and to detect the activity of su-peroxide dismutase(SOD).The quantitative real-time PCR and immunofluorescence were used to detect the prestin expression of mRNA.Results The SOD activity decreased in the HEI-OC1 cells damaged by oxidative stress.The high concentration of the infected group decreased more significantly(F= 9926.293,P<0.01).The expressions of Prestin mRNA and Prestin protein were decreased obviously in the HEI-OC1 cells.The high concentration of in-fected group decreased more significantly (F= 4065.046and7657.217,P<0.01).Conclusion Oxidative stress in-ducing damage inhibits the expression of prestin.Prestin protein may be used as a molecular marker of sensory deafness.