90,180 and 360 mg·kg-1 on general central nervous system (CNS) of mice was investigated by general behavior observation, nembu-tal subthreshold hypnosis experiment, spontaneous activity test and rotary rod test. The changes in blood pressure, heart rate, electro-cardiogram, breathing flow and frequency in anaesthetic Bealge dogs were observed to evaluate the effects of the capsules respectively at the low, medium and high dosage of 16,32 and 64 mg·kg-1 on cardiovascular and respiratory systems. Results:The general behavior of mice was normal after the administration of Sansheng Jindan capsules. The capsules showed no synergetic hypnotic effect on nembu-tal, and had no influence on the spontaneous activity and body coordination ability of mice (P>0. 05). The blood pressure, ECG and respiratory index of anaesthetic Bealge dogs were also normal after the administration of the capsules (P>0. 05). Conclusion:There are no significant effects of Sansheng Jindan capsules at the experimental dosages on central nervous system of mice and respiratory and cardiovascular systems of Beagle dogs.

Objective: Compare the detection result of blood samples of severe fever with thrombocytopenia syndrome (SFTS) patients using different detection techniques, and observe the dynamic characteristics of the virus specific RNA, IgM antibody and IgG antibody, to provide theoretical basis for selection of diagnostic methods of disease. Methods: Acute phase serum of suspected SFTS cases and convalescent serum samples of lab-confirmed cases were collected. Real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay (ELISA) were used to detect the virus specific RNA, IgM antibody and IgG antibody. The detection results of different methods, the relationship between positive results and the acquisition time, and the dynamic characteristics of viral nucleic acid and antibodies were analyzed. Results: A total of 87 serum samples of the suspected SFTS patients were collected, the positive rate of virus specific RNA, IgM antibody and IgG antibody were 53.41%, 31.03% and 3.41%, respectively. Among 55 confirmed cases of SFTS, the consistent rate of virus specific RNA and IgM antibody detection methods was 36.36%, and the difference between the two methods was significant (χ²=6.82, P=0.009), kappa=-0.257. The sampling intervals of RNA positive samples were all within 12 days, of which the positive detection rate was highest after 7-9 days, and the difference was statistically significant (χ²=10.35, P=0.016). In 34 SFTS convalescent serum samples, all the nucleic acid tests were negative, the positive rate of IgM antibody was 41.18%, which was not significantly different from the acute phase serum samples (P=1.00). The positive rate of IgG antibody was 94.12%, which was significantly higher than that of acute IgG antibody (0%). The dynamic characteristics of IgM and IgG antibody showed that IgM antibody could be detected on the second day after onset, the latest detection time was 74 days after onset, and the highest absorbance value and antibody detection rate occurred in 30-60 days. The earliest detection time of IgG antibody was 12 days after onset, and the last detection time was 100 days.The detection rate of IgG antibody and absorbance value increased rapidly after 30 days, and maintained in a high level. The detection rate of IgG antibody was 100% in 30-60 days. Conclusions Blood samples taken from SFTS suspected patients within two weeks of onset may be prioritized for detection of viral nucleic acids using Real-time fluorescence PCR or for detection of IgM antibodies by ELISA. Although IgM antibody can be detected 2 days after the onset, the peak appeared much later, so the negative result can’t rule out the diagnosis. IgG antibody has a high seroconversion rate in convalescent samples, and can be used as an auxiliary tool for disease diagnosis.

Objective:To investigate the effect of fascial iliaca compartment block (FICB) continuous analgesia in the early stage after admission on early postoperative cognitive and motor function in elderly patients with hip fractures.Methods:A total of 80 elderly patients with hip fractures admitted toThe First Affiliated Hospital of Tsinghua University from June 2018 to June 2020 were selected and randomly divided into the control group and the observation group, with 40 cases in each group. The control group adopted the routine postoperative analgesia regimen, while the observation group adopted FICB analgesia immediately after admission to the hospital until before the operation. Postoperative analgesia pattern was consistent with that of the control group, and both groups were given postoperative analgesia for 48 h. The scores of visual analogue scale (VAS), mini mental state assessment scale (MMSE), Harris hip score (Harris) and surgical indexes, stress indexes and incidence of adverse reactions were compared between the two groups.Results:The levels of postoperative blood glucose, cortisol, angiotensin Ⅱin the observation group were lower than those in the control group: (5.21 ± 1.03) mmol/L vs. (7.03 ± 1.06) mmol/L, (643.08 ± 77.28) nmol/L vs. (747.96 ± 82.80) nmol/L, (41.03 ± 5.22) ng/L vs. (57.15 ± 8.16) ng/L, there were statistically differences ( P<0.05). The dosage of sufentanil in the observation group was lower than that in the control group: (27.48 ± 3.25) mg vs. (58.54 ± 4.86) mg, there was statistically difference ( P<0.05). The scores of VAS score at 12 h before surgery, 12 h and 48 h after surgery in the observation group were lower than those in the control group, and the scores of MMSE score were higher than those in the control group, there were statistically differences ( P<0.05). After the surgery, the Harris scores in the observation group was higher than that in the control group: (76.09 ± 6.11) scores vs. (65.62 ± 6.13) scores, there was statistically difference ( P<0.05). The incidence rate of postoperative cognitive dysfunction (POCD) in the observation group was lower than that in the control group: 2.5%(1/40) vs. 15.0%(6/40), there was statistically difference ( χ2 = 3.91, P<0.05). Conclusions:FICB continuou sanalgesic in the early stage after admission of elderly patients with hip fracture is satisfactory, which can effectively relieve postoperative pain, while the stress response is relatively mild, the recovery of postoperative cognitive function and hip function is good.

OBJECTIVE To generate hemophilia A (HA) patient-specific inducible pluripotent stem cells (iPSCs) and induce endothelial differentiation. METHODS Tubular epithelial cells were isolated and cultured from the urine of HA patients. The iPSCs were generated by forced expression of Yamanaka factors (Oct4, Sox2, c-Myc and Klf4) using retroviruses and characterized by cell morphology, pluripotent marker staining and in vivo differentiation through teratoma formation. Induced endothelial differentiation of the iPSCs was achieved with the OP9 cell co-culture method. RESULTS Patient-specific iPSCs were generated from urine cells of the HA patients, which could be identified by cell morphology, pluripotent stem cell surface marker staining and in vivo differentiation of three germ layers. The teratoma experiment has confirmed that such cells could differentiate into endothelial cells expressing the endothelial-specific markers CD144, CD31 and vWF. CONCLUSION HA patient-specific iPSCs could be generated from urine cells and can differentiate into endothelial cells. This has provided a new HA disease modeling approach and may serve as an applicable autologous cell source for gene correction and cell therapy studies for HA.
Cell Differentiation ; Hemophilia A ; pathology ; therapy ; urine ; Humans ; Induced Pluripotent Stem Cells ; cytology ; transplantation ; Urine ; cytology

Objective:To study the epidemiological characteristics and spatio-temporal aggregation of hemorrhagic fever with renal syndrome (HFRS) in Shandong Province, and to provide reference for formulating reasonable prevention and control strategies.Methods:Retrospective analysis was used to collect HFRS surveillance data and confirmed case data in Shandong Province from 2017 to 2020 in the "China Disease Prevention and Control Information System Infectious Disease Surveillance System". Geoda 1.18 software was used for global and local spatial autocorrelation analysis, SaTScan 9.6 software was used for spatio-temporal scanning analysis, and ArcGis 10.7 software was used for map drawing and visual display.Results:A total of 3 753 cases of HFRS were reported in Shandong Province from 2017 to 2020, including 56 deaths. The annual incidence rate was 1.26/100 000, 1.22/100 000, 0.75/100 000 and 0.53/100 000, respectively, with an average annual incidence rate of 0.94/100 000. The incidence of HFRS was obviously seasonal, mainly concentrated in autumn and winter from October to December, accounting for 50.41% (1 892/3 753). The age of onset was mainly 30-59 years old, accounting for 61.68% (2 315/3 753). The male to female ratio was 2.76 ∶ 1.00 (2 756 ∶ 997). The occupation distribution was mainly farmers, accounting for 81.99% (3 077/3 753). The global spatial autocorrelation analysis showed that HFRS showed spatial aggregation areas in each year from 2017 to 2020 (Moran' I = 0.38, 0.33, 0.59, 0.46, Z = 7.47, 7.23, 10.69, 8.66, P < 0.001). The local spatial autocorrelation analysis showed that "high-high" aggregation areas were mainly concentrated in central and southeast of Shandong Province, while "low-low" aggregation areas were mainly concentrated in northwest of Shandong Province. Spatio-temporal scanning analysis revealed 1 type Ⅰ agglomerations and 2 type Ⅱ aggregation areas. The type Ⅰ aggregation areas occurred from October to November 2018, covering 22 counties (districts) of 5 cities in Qingdao, Yantai, Weifang, Weihai and Rizhao. The first type Ⅱ aggregation area occurred from October to November 2017, involving 23 counties (districts) of 8 cities in Jinan, Zibo, Zaozhuang, Weifang, Jining, Tai 'an, Rizhao and Linyi. The second type Ⅱ aggregation area occurred in Jinxiang County, Jining City from February to March 2017. Conclusion:The incidence of HFRS in Shandong Province from 2017 to 2020 has obvious spatio-temporal aggregation, and the hot spots are concentrated in central and southeast of Shandong Province, which should be regarded as a key area for prevention and control of HFRS.

Objective:To explore the epidemiologic characteristics of long-lived population and influencing factors in Shanglin county of Guangxi and provide scientific basis for the study of health and longevity in Guangxi.Methods:We collected and analyzed the general demographic cross-sectional data of the long-lived individuals (≥90 years old) in 11 villages and towns by multi-source registration and face-to-face interview. The age group control design was adopted to conduct a comparison among the longevity group (90-100 years old), centenarian group (≥100 years old), the longevity plus centenarian group and control group (local population aged 40-85 years), and identify the factors related to longevity.Results:Among the 496 007 people registered in Shanglin, 1 533 were aged ≥90 years, including 1 453 in the longevity group, with an average age of (92.84±2.46) years, and 80 in the centenarian group, with an average age of (102.67±2.60) years. The spatial distribution of long-lived individuals and centenarians was mainly in the north and central areas, and sparse in southwest area. Analysis on factors related to health and longevity indicated that old people with Zhuang ethnic ( OR=1.551,95% CI:1.308-1.838), married ( OR=55.507,95% CI:36.087-85.377) and moderately high waist-to-hip ratio ( OR=258.056,95% CI:27.775-2 397.569), and SBP ( OR=1.019,95% CI:1.013-1.026) tended to live longer. Conclusions:We found that the rate of longevity in Shanglin was higher than the average level in Guangxi and China. Longevity in Shanglin country had unique spatial and population distribution characterics of female longevity more than male longevity, mainly Zhuang ethnic and so on. Being women, married, family history of longevity, appropriate high waist-to-hip ratio, SBP and blood sugar level might be positive factors for longevity in Shanglin, but the impacts of other factors on longevity need further study.

Objective To compare the therapeutic effects between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in patients with stage Ⅱ/Ⅲ esophageal cancer and investigate the prognostic factors.Methods Medical record of 2 132 patients with stage Ⅱ/Ⅲ esophageal cancer who underwent definitive radiotherapy with/without chemotherapy in 10 hospitals from January 2002 to December 2016 from were retrospectively analyzed.Among these patients,37.9％ of them were aged ≥ 70 years,33.9％ with neck and upper esophageal tumors and 66.1％ with middle and lower esophageal and borderline tumors.The median gross tumor volume (GTV) and lymph node gross tumor volume (GTVnd) was 41.6 cm3.Among them,32％ were stage Ⅱ] and 68％ were stage Ⅲ.A total of 723 patients received 3DCRT and 1 409 cases received IMRT.Patients received an equivalent dose in 2 Gy (EQD2) ≥ 60 Gy accounted for 86.1％,and 41.1％ of them received concurrent chemoradiotherapy.Results The median follow-up time was 60.8 months.The 1-,3-and 5-year overall survival (OS) of all patients was 73.9％,41.7％ and 32.6％,and the 1-,3-and 5-year progression-free survival (PFS) was 62.2％,37.3％ and 32％,respectively.Multivariate analysis demonstrated that age,primary tumor location,clinical stage,tumor target volume,EQD2 and concurrent chemoradiotherapy were the independent prognostic factors for OS.Age,primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS.The OS and PFS did not significantly differ among the low-risk,low-/moderate-risk,moderate-/high-risk and high-risk groups according to age≥70 years,tumor diameter＞5 cm,tumor volume ≥41.6 cm3 and stage Ⅲ (P＜0.001).After the propensity score matching (PSM) method,neither 3DCRT nor IMRT yielded significant advantages in OS or PFS (P=0.971;P=0.658).However,IMRT tended to yield survival benefits in low-risk patients (P=0.125).Conclusions Both 3DCRT and IMRT yield relatively high OS rate in patients with stage Ⅱ/Ⅲ esophageal cancer.The prognosis model established in this investigation can properly predict the survival of patients.Low-risk patients tend to obtain survival benefits from IMRT.

Objective To retrospectively analyze the effect of tumor length on the prognosis in stage Ⅱ/Ⅲ esophageal squamous cell carcinoma (ESCC) patients treated with definitive radiotherapy and to evaluate the role of tumor length in clinical stage for non-operative ESCC patients.Methods The data of 2 086 ESCC patients who were treated with definitive radiotherapy from 2002 to 2016 in 10 hospitals (3JECROG) were analyzed.The effect of tumor length on overall survival (OS) was analyzed and stratified analysis of tumor length was done in different stages of ESCC.Results The median OS and median progression-free survival (PFS) time of the whole group were 25.6 months and 18.2 months respectively.The Cox multivariate analysis showed that treatment moda,aga,alinical stage and tumor length were independent prognostic factors.The median,1-,3-,and 5-year OS were 28.9 months,77.3％,45.0％,and 36.3％ versus 21.9 months,69.9％,37.9％,and 28.1％ for patients with ≤ 5 cm and patients ＞ 5 cm respectively (P＜0.05).For stage Ⅱ patienta,abe median OS were 42.1 and 38.9 months respectively in ≤ 5 cm group and＞5 cm group (P=0.303).And for stage Ⅲ patienta,abe median OS were 23.9 and 19.3 months respectively in ≤5 cm group and＞5 cm group (P＜0.001).The median OS with N1was 24.1 and 18.4 montha,aespectively in ≤5 cm group and＞5 cm group (P＜0.001).Conclusions The tumor length was an independent prognostic factor for stage Ⅱ/Ⅲ patients treated definitive radiotherapy.The tumor length may be helpful in clinical staging of ESCa,aspecially for stage Ⅲ and N1.

Objective:To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation.Methods:The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed.Results:The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups ( P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy ( P<0.05). Multivariate analysis demonstrated that PGTV dose ( OR=0.693, P=0.004), radiation esophagitis ( OR=0.867, P=0.038), and radiation pneumonia ( OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions:For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.