ObjectiveTo establish a method for the determination of 1,1,1,2-tetrachloroethane (TeCA) and 1,1,2,2-TeCA in human urine using liquid-liquid extraction-gas chromatography. Methods The 5.0 mL urine sample was mixed with 2.0 g anhydrous sodium sulfate and 5.0 mL ethyl acetate, then vortexed mixing. The 1.0 mL extraction was separated by 100% dimethylpolysiloxane capillary gas chromatography column, detected by flame ionization detector, and quantified by an external standard method. Results The linear ranges of 1,1,1,2-TeCA and 1,1,2,2-TeCA were 0.250-50.750 mg/L, with both correlation coefficients of >0.999 9. The detection limit of 1,1,1,2-TeCA in urine was 0.020 mg/L, and the lower limit of quantification was 0.060 mg/L. The average recovery was 88.02%-101.32%, and the within-run and between-run relative standard deviations (RSDs) were 0.11%-0.47% and 0.39%-1.09%, respectively. The detection limit of 1,1,2,2-TeCA in urine was 0.050 mg/L, and the lower limit of quantification was 0.150 mg/L. The average recovery was 93.42%-101.32%, and the within-run and between-run RSDs were 0.28%-1.04% and 0.50%-1.03%, respectively. Both the 1,1,1,2-TeCA and 1,1,2,2-TeCA cannot be stored at room temperature. The 1,1,2,2-TeCA can be stored at 4 ℃ for at least three days. At -20 ℃, the 1,1,1,2-TeCA can only be stored for one day, while 1,1,2,2-TeCA can be stored for at least five days. Conclusion This method has high sensitivity, good specificity, simple sample pretreatment, and more intuitive and reliable results. It can be used to determine the level of 1,1,1,2-TeCA and 1,1,2,2-TeCA in urine of occupational population.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To establish a high performance liquid chromatography (HPLC) method for simultaneous determination of six aniline compounds (ADs) in workplace air. Methods GDH-1 air sampling tube was used to collect six co-existing ADs such as aniline, o-toluidine, N-methylaniline, m-methylaniline, p-methylaniline and N,N-dimethylaniline in the vapor and aerosol of workplace air. The samples were desorbed and eluted using a methanol solution containing 1.00% ammonia water, followed by separation on a C₁₈ chromatographic column and detection using a diode array detector. Results The quantification range of the method was 0.19 -253.50 mg/L, with the correlation coefficient of 0.999 9 for all six ADs. The minimum detection range was 0.02-0.06 mg/m³, and the minimum quantitation range was 0.04-0.19 mg/m³ [both calculated for a 15.0 L sample with a desorption (elution) solution volume of 3.00 mL]. The average desorption and elution efficiencies were 92.15%-104.41% (silica gel) and 94.29%-104.29% (filter membrane). The intra-assay relative standard deviation (RSD) ranged from 0.90%-9.72% (silica gel) and 0.57%-6.96% (filter membrane). The inter-assay RSD ranged from 2.03%-9.78% (silica gel) and 2.50%-8.62% (filter membrane). The samples were stable at room temperature for seven days. Conclusion This method can be used for the simultaneous determination of six ADs in workplace air.

Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ²=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ²=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ²=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.
Male ; Female ; Child ; Humans ; Child, Preschool ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Retrospective Studies ; Survival Analysis ; Mutation ; Hematopoietic Stem Cell Transplantation

Objective:To explore the clinical effect of laparoscopic anatomical hepatic segment Ⅷ (S8) resection.Methods:Of 16 patients with liver cancer who underwent laparoscopic anatomical hepatic S8 resection at the National Cancer Center from October 2020 to October 2022 were were enrolled, including 13 males and 3 females, aged (59.1±10.9) years. The operation time, intraoperative blood loss, occurrence of intraoperative blood transfusion, and postoperative complications were retrospectively analyzed. Recurrence and survival were followed up by outpatient and telephone reviews.Results:Laparoscopic anatomical hepatic S8 resection was successfully performed in 16 patients without conversion to laparotomy. Among them, 10 patients underwent the intraoperative ultrasound guided hepatic parenchymal approach, and 6 underwent laparoscopic Glissonean pedicle puncture for the positive staining of S8 using indocyanine green. The operation time was (274.8±82.8) min, and the intraoperative blood loss was [ M( Q1, Q3)] 100.0 (50.0, 200.0) ml. There were no intraoperative blood transfusion or postoperative complication. The drainage tube was successfully removed and the patients were discharged 5 to 7 days after surgery. The patients were followed up for 5 to 24 months and all survived. Two patients had tumor recurrence. Conclusion:Laparoscopic anatomical S8 resection is safe and feasible.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To establish a solvent desorption-gas chromatography method for the determination of 1,1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane in workplace air. Methods: The 1,1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane in workplace air were collected using activated carbon tubes, desorbed with carbon disulfide, and separated and detected by gas chromatography. The quantifications were based on standard curves. Results: The linear ranges of 1,1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane were 0.98-395.50 and 0.87-395.50 mg/L, respectively, with the correlation coefficient of 0.999 95. The detection limits were 0.29 and 0.26 mg/L, respectively. The average of desorption efficiency was 92.04%-104.67%. The within- and between-run relative standard deviations were 1.42%-2.09% and 1.63%-6.09%, respectively. The sampling efficiency was more than 98.00%. The samples could be stored at room temperature for at least 14 days. Conclusion: This method can be used in detection of 1,1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane in workplace air.

Objective: To understand the virulence gene and drug resistance profile of Shigella sonnei outbreak in Huainan city, and conduct pathogenic traceability analysis. Methods: Water samples and feces related to an infectious diarrhea outbreak in Huainan city in August 2020 were collected for multiple pathogen detection. Virulence gene, drug sensitivity, pulse-field gel electrophoresis and whole genome sequencing of Shigella isolates were analyzed respectively. Results: 38 strains of Shigella sonnei were detected in 56 samples of mucilage feces with a positive rate 67.86%, and all serotypes were Shigella sonnei Phase I. Three strains of Shigella sonnei were detected by fluorescence PCR in the Gram-negative (GN) bacterial enrichment solution of terminal water and well water. Virulence genes were ipaH positive (38), ipaH/ial (31) and ipaH/ial/sen positive (1), respectively. The drug resistance spectrum showed that 9 of 14 antibiotics were 100% resistant, and only imipenem, chloramphenicol, ceftazidime and ciprofloxacin were effective drugs. XbaⅠ restriction enzyme map type of 36 isolates was completely consistent, and the ST type analysis of 3 strains was ST152. Whole genome sequencing and analysis verified that the outbreak was caused by a single clonal group of strains, and revealed that the isolates of the outbreak were clustered into a large cluster with 3 Chinese strains and 1 Korean strain in the database, far away from the strains of other countries. Conclusion: The outbreak is caused by a single clone of Shigella sonnei, which are low virulence strains and have multiple drug resistance.
Disease Outbreaks ; Dysentery, Bacillary/microbiology* ; Humans ; Shigella ; Shigella sonnei/genetics* ; Water/pharmacology*

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To study the use of the Glissonean pedicle approach based on the triangular area among the right anterior pedicle, the right posterior pedicle and the right hepatic vein ( "APR triangle" ), followed by indocyanine green fluorescence negative staining in laparoscopic anatomical resection of right hepatic segments.Methods:The clinical data of 34 patients with liver tumors who underwent laparoscopic anatomical right hepatic segmentectomy at the Chinese Academy of Medical Sciences and Peking Union Medical College from September 2020 to September 2021 were analyzed retrospectively. Of the 34 patients, there were 24 males and 10 females, aged (58.3±10.3) years old. Data on completion of operation, operation time, intraoperative blood loss, intraoperative blood transfusion, postoperative complications and postoperative hospital stay were collected.Results:All the 34 patients had malignant liver tumors, and they were successfully operated using total laparoscopic surgery. There was no conversion to open surgery. Three patients underwent segment V resection, 3 patients segment VI resection, 5 patients segment VII resection, 2 patients segment V + segment VI resection, 9 patients segment VI + segment VII resection, 3 patients segment V + segment VII resection, 5 patients segment V dorsal segment + segment VI + segment VII resection, 3 patients right posterior section resection + anterior dorsal segment resection and 1 patient anterior dorsal section resection. The operation time was (275.58±82.28) min, the amount of intraoperative blood loss was 100(100, 300) ml, and there were no patients requiring blood transfusion during the operation. Liquid food was started on the first day after operation, and out-of bed activities were carried out on the second to third days after operation. The Clavien Dindo classification of postoperative complications was grade I in 32 patients and grade III in 2 patients. The postoperative hospital stay was (7.23±3.10) d. All tumor margins were negative for malignancy. All the 34 patients were followed-up for (8.94±2.94) months. By the end of follow-up, 34 patients had survived without tumor recurrence.Conclusion:The right Glisson pedicle approach based on the "APR triangle" and the anatomical resection of right hepatic segments with fluorescence negative staining were safe and feasible.