Objective:This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects.Methods:A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments.Results:Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively ( P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively ( P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% ( P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion:Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.

Objective To explore the correlations of serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) with grading of myelofibrosis (MF) in patients with myeloproliferative neoplasms (MPN). Methods Ninety patients with Philadelphia chromosome negative (Ph-)MPN were selected as MPN group. According to the grading criteria for myelofibrosis by the World Health Organization (WHO) in 2016, MPN patients were divided into pre-fibrosis or early fibrosis group with 54 cases and significant fibrosis group with 36 cases; another 50 healthy volunteers were selected as the control group. Levels of serum VEGF, MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay, and the ratio of TIMP-1 to MMP-9 (TIMP-1/MMP-9) was calculated. Spearman rank correlation test was used to analyze the correlations of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 with MF grading. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of each indicator alone or their combination for diagnosing MPN or distinguishing MF grading. Results Compared with the control group, the serum levels of VEGF, MMP-9 and TIMP-1 in the MPN group increased significantly (P < 0.05). Values of area under the curve (AUC) of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for diagnosing MPN were 0, 834, 0.745, 0.923 and 0.618 respectively; the AUC of the combined diagnosis of MPN by VEGF, MMP-9 and TIMP-1 was 0.960; when the optimal cut-off value was 0.627, the sensitivity was 85.56%, and the specificity was 92.00%. Compared with the pre-fibrosis or early fibrosis group, the serum levels of VEGF, TIMP-1 and TIMP-1/MMP-9 in the significant fibrosis group increased significantly (P < 0.05). Spearman correlation analysis showed that VEGF (r=0.378, P=0.001), TIMP-1 (r=0.512, P < 0.001) and TIMP-1/MMP-9 (r=0.353, P=0.001) were positively correlated with the MF grading of MPN patients (P < 0.05). ROC curve analysis showed that the values of AUC of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis were 0.723, 0.523, 0.802 and 0.708 respectively; the AUC of the combined detection of VEGF, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis was 0.838; when the optimal cut-off value was 0.530, the sensitivity was 72.22%, and the specificity was 85.19%. Conclusion Serum VEGF, TIMP-1 and TIMP-1/MMP-9 can reflect the MF progression of MPN patients, and the combined detection of these indicators can predict the MF degree of MPN patients.

OBJECTIVE To observe the effects of chlorogenic acid on the activation of macrophage induced by lipopolysaccharide （LPS）， and to explore the role of triggering receptors expressed on myeloid cells-2 （TREM2） in the action. METHODS To find a suitable LPS concentration， the cells were cultured with 1， 10 and 100 ng/mL LPS for 24 h. The level of interleukin 6 （IL-6） in the cell culture supernatant and protein expression of inducible nitric oxide synthase （iNOS） in the cells were detected. To search for a suitable chlorogenic acid concentration， the cells were divided into control group， LPS group and three chlorogenic acid （0.01， 0.1 and 1 μmol/L）+LPS groups. The levels of tumor necrosis factor α （TNF-α） and IL-1β in the cell culture supernatant， the protein expressions of iNOS and TREM2 in the cells and cell viability were detected. To observe the effects of TREM2 in chlorogenic acid alleviating macrophage activation， TREM2-small interfering RNA （TREM2-siRNA） was taken to intervene in TREM2 protein expression. The cells were divided into control group， LPS group， chlorogenic acid+LPS group， TREM2-siRNA+chlorogenic acid+LPS group and SC-siRNA+chlorogenic acid+LPS group. After 24 h incubation， the levels of TNF- α and IL-1β in the cell culture supernatant and protein expressions of TREM2， iNOS and nuclear factor κB p65 （NF-κB p65） in the cells were detected. RESULTS 10 ng/mL LPS promoted IL-6 release and increased iNOS protein expression， and 10 ng/mL LPS was taken in the next experiments. Compared with the LPS group， 0.1 μmol/L chlorogenic acid decreased TNF-α jiaji1981@126.com and IL-1β levels， and down-regulated iNOS expression，meanwhile increased TREM2 expression without effect on cell viability， and 0.1 μmol/L chlorogenic acid was taken in the next experiments. Compared with the control group， the protein expressions of iNOS and NF- κB p65 in the LPS group were significantly increased （P＜0.05）； compared with the LPS group， the protein expressions of iNOS and NF- κB p65 in the chlorogenic acid+LPS group were significantly decreased， the protein expressions of TREM2 was significantly increased （P＜ 0.05）； compared with the chlorogenic acid+LPS group， the protein expressions of iNOS and NF-κB p65 of TREM2-siRNA+ chlorogenic acid+LPS group were significantly increased， the protein expressions of TREM2 was significantly decreased （P＜0.05）. TREM2-siRNA could significantly reverse the above effects of chlorogenic acid， while SC-siRNA did not significantly affect the above anti-inflammatory effects of chlorogenic acid. CONCLUSIONS Chlorogenic acid can inhibit the LPS-induced macrophage activation， and its anti-inflammatory may be mediated by TREM2 protein.

This study aimed to quantitatively assess the effectiveness of the Wuhan lockdown measure on controlling the spread of coronavirus diesase 2019 (COVID-19). : Firstly，estimate the daily new infection rate in Wuhan before January 23，2020 when the city went into lockdown by consulting the data of Wuhan population mobility and the number of cases imported from Wuhan in 217 cities of Mainland China. Then estimate what the daily new infection rate would have been in Wuhan from January 24 to January 30th if the lockdown measure had been delayed for 7 days，assuming that the daily new infection in Wuhan after January 23 increased in a high，moderate and low trend respectively (using exponential, linear and logarithm growth models). Based on that，calculate the number of infection cases imported from Wuhan during this period. Finally，predict the possible impact of 7-day delayed lockdown in Wuhan on the epidemic situation in China using the susceptible-exposed-infectious-removed (SEIR) model. : The daily new infection rate in Wuhan was estimated to be 0.021%，0.026%，0.029%，0.033% and 0.070% respectively from January 19 to January 23. And there were at least 20 066 infection cases in Wuhan by January 23，2020. If Wuhan lockdown measure had been delayed for 7 days，the daily new infection rate on January 30 would have been 0.335% in the exponential growth model，0.129% in the linear growth model，and 0.070% in the logarithm growth model. Correspondingly，there would have been 32 075，24 819 and 20 334 infection cases travelling from Wuhan to other areas of Mainland China，and the number of cumulative confirmed cases as of March 19 in Mainland China would have been 3.3-3.9 times of the officially reported number. Conclusions: Timely taking city-level lockdown measure in Wuhan in the early stage of COVID-19 outbreak is essential in containing the spread of the disease in China.
COVID-19 ; China/epidemiology* ; Cities ; Communicable Disease Control ; Humans ; SARS-CoV-2

To predict the epidemiological trend of coronavirus disease 2019 (COVID-19) by mathematical modeling based on the population mobility and the epidemic prevention and control measures. : As of February 8，2020，the information of 151 confirmed cases in Yueqing，Zhejiang province were obtained，including patients' infection process，population mobility between Yueqing and Wuhan，etc. To simulate and predict the development trend of COVID-19 in Yueqing, the study established two-stage mathematical models，integrating the population mobility data with the date of symptom appearance of confirmed cases and the transmission dynamics of imported and local cases. : It was found that in the early stage of the pandemic，the number of daily imported cases from Wuhan (using the date of symptom appearance) was positively associated with the number of population travelling from Wuhan to Yueqing on the same day and 6 and 9 days before that. The study predicted that the final outbreak size in Yueqing would be 170 according to the number of imported cases estimated by consulting the population number travelling from Wuhan to Yueqing and the susceptible-exposed-infectious-recovered (SEIR) model; while the number would be 165 if using the reported daily number of imported cases. These estimates were close to the 170，the actual monitoring number of cases in Yueqing as of April 27，2020. : The two-stage modeling approach used in this study can accurately predict COVID-19 epidemiological trend.
COVID-19 ; China/epidemiology* ; Disease Outbreaks ; Humans ; Models, Theoretical ; Pandemics ; SARS-CoV-2

Objectives:To investigate the nursing effect of perioperative enhanced recovery after surgery（ERAS）management model in elderly patients with hip fracture.Methods:A retrospective case-control study was conducted to analyze the clinical data of 94 elderly patients with hip fracture admitted to Second Affiliated Hospital of Soochow University from July 2017 to June 2018，including 24 males and 70 females aged 76-98 years［（83.7±5.4）years］. There were 54 patients with intertrochanteric fracture and 40 patients with femoral neck fracture. Surgical method was proximal femoral nail antirotation（PFNA）fixation or artificial hip arthroplasty. A total of 44 patients were managed by ERAS（enhanced recovery group）and 50 patients by traditional nursing（traditional rehabilitation group）. The off-bed time was compared between the two groups from aspects of different fracture sites，bone mineral density and causes of injury. The visual analogue scale（VAS）was tested preoperatively and at postoperative days 1，3 and 7. The complications were recorded at postoperative 1 month. The activity of daily living（ADL）score was assessed preoperatively and at postoperative 1 week，1 month and 3 months. The Harris hip score was assessed at postoperative 1 week，1 month，3 months and at the last follow-up. The length of hospital stay and death at postoperative 3 months and at the last follow-up were recorded.Results:All patients were followed up for 12-24 months［（17.7±6.2）months］. In enhanced recovery group，the off-bed time of patients with different fracture sites（femoral neck，femoral intertrochanter），bone mineral density（>-2.5 SD，≤-2.5 SD）and causes of injury（falls，traffic accidents and others）were markedly shortened as compared with traditional rehabilitation group（ P<0.01）. There was no significant difference in VAS between the two groups before operation（ P>0.05）. However，the VAS in enhanced recovery group was（3.4±0.9）points，（2.7±0.5）points，（1.7±0.6）points at postoperative days 1，3 and 7，significantly lower than that in traditional rehabilitation group［（4.3±1.1）points，（3.5±0.5）points，（2.7±0.9）points］（ P<0.01）. One month after operation，the incidence of pulmonary infection was 0% in enhanced recovery group and 28%（14/50）in traditional rehabilitation group（ P<0.01）. While there showed no significant differences in incidences of cardiovascular system，nervous system，urinary tract infection，lower limb deep vein thrombosis，impaired liver and kidney function，anemia，electrolyte disorder or hypoalbuminemia between the two groups（ P>0.05）. There was no significant difference in preoperative ADL score between the two groups（ P>0.05）. The ADL score in enhanced recovery group was（37.0±6.6）points，（70.1±8.4）points，（86.2±9.3）points at postoperative 1 week，1 month and 3 months，significantly higher than that in traditional rehabilitation group［（26.5±10.4）points，（50.1±11.4）points，（70.7±9.0）points］（ P<0.01）. The Harris hip score in enhanced recovery group was（80.9±8.6）points at postoperative 1 month，significantly higher than that in traditional rehabilitation group［（71.1±9.2）points］（ P<0.01）. There were no significant differences in Harris hip score between the two groups at postoperative 1 week，3 months and at the last follow-up（ P>0.05）. The length of hospital stay was（4.7±2.4）days in enhanced recovery group，significantly shorter than（7.8±3.9）days in traditional rehabilitation group（ P<0.01）. The enhanced recovery group showed no death within 3 months after operation and 2 deaths［5%（2/44）］at the last follow-up，while the traditional rehabilitation group revealed 4 deaths［8%（4/50）］within 3 months after operation. There was no significant difference in the mortality between the two groups until the last follow-up（ P>0.05）. Conclusion:For elderly patients with hip fracture，perioperative ERAS management model can effectively shorten periods in bed，relieve postoperative pain，reduce incidence of postoperative pulmonary infection，accelerate recovery of hip function，improve quality of life，shorten length of hospitalization and promote early recovery.

OBJECTIVE: To assess the effect of ergonomic factor load on work-related musculoskeletal disorders(WMSDs) in shipyard workers. METHODS: A total of 751 shipyard workers were selected as the research subjects using judgment sampling method. The exposure level of adverse ergonomic factors was assessed using the Quick Exposure Check method. The prevalence of WMSDs was investigated using the revised Musculoskeletal Disorders Investigating Questionnaire of our research group, and the relationship between them was analyzed. RESULTS: The proportions of high or very high level of work load exposure to the neck, back, shoulder and hand in shipyard workers from high to low were 66.4%, 63.5%, 59.8% and 43.7%(P<0.01) respectively. The proportions of occupational stress, driving, vibration and working rhythm at high or very high exposure level were 20.0%, 4.1%, 22.9% and 3.2%, respectively. The prevalence of WMSDs in four body parts of shipyard workers from high to low was the back, neck, hand and shoulder(the prevalence were 44.2%, 31.2%, 26.9% and 26.6%, respectively, P<0.01). After excluding the influence of confounding factors, multiple logistic regression analysis showed that the higher the labor load exposure level and longer of the vibration tool using, the higher the risk of shoulder WMSDs [odds ratio(OR) and 95% confidence interval(CI) were 1.25(1.04-1.51) and 1.33(1.05-1.69), respectively, P<0.05]. The higher the level of occupational stress, the higher the risk of back and neck WMSDs [OR(95%CI) was 1.29(1.05-1.58) and 1.42(1.15-1.77), respectively, P<0.05]. CONCLUSION: There was a dose-effect relationship between the exposure level of shoulder load, the time of using vibration tools and the shoulder WMSDs, and there was a dose-effect relationship between the occupational stress level and the WMSDs in the back and neck.

Objective To observe the effect of a hypoxia mimicking agent deferoxamine (DFO) on the mineral density,volume,architecture,strength,and metabolism of the bones in type 1 diabetic mice withosteoporosis.Methods Type 1 diabetic mice model was established by intraperitoneal injections of streptozotocin.The mice were divided into control (normal mice),diabetes mellitus,and DFO groups.Micro-CT was used to analyze the bone mineral density,volume,architecture,and strength of the trabecule in the distal part of femurs.Three point bending test was carried out to evaluate the bone strength.Hematoxylin and eosin (HE) staining was performed to observe the alteration in the number of osteoblasts.Real-time PCR was used to detect the mRNA expressions of Runt-related gene 2 (Runx-2),osteoclacin,and tartrate resistant acid phosphatase (TRAP) in tibias.Western blot was used to detect the protein expressions of Hypoxia-inducible factor-1α(HIF-1α) and vascular endothelial growth factor (VEGF) in tibias.Results There was a decrease in mineral density,volume,strength of bones as well as deteriorated trabecular microarchitecture in diabetic mice as compared to control mice,which were partially improved by DFO treatment.Moreover,DFO treatment increased the number of osteoblasts and mRNA expression levels of Runx-2,osteoclacin,TRAP,as well as protein expression levels of HIF-1 α and VEGF(P＜0.05).Conclusion Bone loss could be partially prevented by DFO treatment in type 1 diabetic osteoporosis mice,which might be ascribed to increased bone formation via stimulating hypoxia inducible factor singnaling pathway.

Objective To evaluate the efficacyof the first line chemotherapy FOLFIRINOX (5-Fu,Leucovorin calcium,Irinotecan,Oxaliplatin) as the treatment of pancreatic cancer.Methods Pertinent studies were identified from the PubMed,Cochrane Library and EMBASE.The outcomes were resection rate and radical (R0) resection rate were analyzed.Data were expressed as weighted pooled proportions with 95％ confidence intervals (95％ CI).Results There were thirteen studies with 408 patients with LAPC and BRPC included.After the treatment,42.0％ (95％ CI:28.0％ ～56.0％) tumorswere resected and 41.0％ (95％ CI:37.0％ ～45.0％) were underwentR0 resection,and median overall survival ranged from 15.5 to 34.5 months,median progression-free survival ranged from 10.0 to 17.8 months.Conclusion The meta-analysis shows that down-staging after first line FOLFIRINOX-based therapy is noticeable in patients with borderline resectable/unresectable PC,and the adverse events were in control.

Objective To investigate the effect of coupled plasma filtration adsorption (CPFA) on plasma cytokines:TNF-α,IL-1β,IL-6,cellular immunity,blood lactate acid concentration,heart rate,respiration rate,oxygenation index,hemodynamics,blood cells counts,and prognosis in patients with multiple organ dysfunction syndromes (MODS).Methods This was a prospective,randomized clinical trial in 45 patients diagnosed as MODS.Patients were randomly assigned to hemoperfution with resin adsorption (HP) + continuous venous-venous hemofiltration (CVVH) group,CPFA group and CVVH group.The general clinical data,APACHE Ⅱ score,number of failure organ and previous mentioned biomarkers were documented.Blood samples were collected before and after blood filtration with any one of these procedures.The plasma samples were isolated and stored with frozen at-60 ℃.Data were statistically analyzed with SPSS 13.0 version software.Results In CPFA group,plasma cytokines,TNF-α、IL-1β、IL-6,decreased markedly after plasma adsorption for two hours (P ＜ 0.01);and plasma concentrations of IL-6 were further descended after subsequent CVVH for 10 hours (P ＜ 0.05).In HP + CVVH group,plasma cytokines,TNF-α、IL-1β、IL-6,decreased markedly after HP (P ＜ 0.01),and plasma concentrations of IL-6 were further descended after subsequent CVVH for 10 hours (P ＜ 0.05).In CVVH group,plasma cytokines,TNF-α、IL-1β、IL-6,decreased after CVVH for 12 hours (P ＜ O.05).Blood lactate acid concentration,heart rate,respiration rate,oxygenation index,T-lymphocytes subgroups (CD3 +,CD4 +,CD8 +,CD4 +/CD8 + ratio),clinical symptoms were improved and dose of vasoactive agent was reduced in the patients of three groups without differences among them.The counts of red blood cells,white blood cells and platelets after CPFA and CVVH showed no significant changes.There was no significant difference in blood cell counts between CPFA and CVVH groups.After HP + CVVH,there was a trend of decrease in platelet count (P ＜ 0.05).Platelet counts were significanfly higher in patients treated with CPFA and CVVH group than those in patients treated with HP + CVVH group (P ＜ 0.05).There were 6 patients died in HP + CVVH group,6 patients died in CPFA group and 5 patients died in CVVH group within 28days.Conclusions The comparison of efficacy of blood filtration among 3 modalities of HP + CVVH,CPFA and CVVH showed CPFA had higher capacity of Inflammatory medium scavenging than CVVH,and had less damage effect on blood visible component,especially on platelet compared with HP + CVVH.CPFA was an effective and safety modality in the treatment of the patients with multiple organ dysfunction syndrome.