Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective:To investigate the effect of TLK2 expression regulated by miR-21 on proliferation and apoptosis of acute myeloid leukemia cells.Methods:Seventy patients with AML admitted to our hospital from January 2019 to July 2022 were selected,while 30 patients with iron deficiency anemia were selected as the control group.Bone marrow mononuclear cells(BMMNCs)of the patients were obtained using Ficoll density gradient centrifugation.RT-qPCR was used to determine the expression levels of miR-21 and TLK2 mRNA in BMMNCs.Mimics-miR-21,mimics-NC,inhibitor-miR-21,inhibitor-NC and NC were transfected into HL-60 cells using liposome-mediated transfection technology.CCK-8 method was used to determine the activity of transfected HL-60 cells after treatment with cytarabine.The apoptosis rate of HL-60 transfected cells was determined by TUNEL method.The expression of TLK2 mRNA in HL-60 cells transfected with inhibitor-miR-21 was determined by RT-qPCR.Results:The relative expression levels of miR-21 and TLK2 mRNA in BMMNCs of AML patients were significantly higher than those of controls(both P＜0.05).After HL-60 cells were treated with cytarabine,both the cell activity of inhibitor-miR-21 group and mimics-miR-21 group decreased significantly with the increase of cytarabine concentration(both P＜0.05).However,at each concentration point of cytarabine,the cell activity of inhibitor-miR-21 group was lower than that of control group(P＜0.05),while mimics-miR-21 group was higher than control group(P＜0.05).After HL-60 cells were treated with cytarabine,the apoptosis rate of inhibitor-miR-21 group was significantly increased(P＜0.05),while that of mimics-miR-21 group was significantly decreased(P＜0.05).After HL-60 cells were treated with inhibitor-miR-21,the relative expression of TLK2 mRNA decreased significantly(P＜0.05).Conclusion:miR-21 is highly expressed in AML patients,which may promote the apoptosis of AML cells by inhibiting the expression of TLK2.

OBJECTIVE: This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline (BR) and the conventional treatment regimen (CR, not containing Bedaquiline) for the treatment of adults with multidrug-resistant tuberculosis (MDR-TB) in China. METHODS: A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years. The model parameter data were synthesized from the literature, the national TB surveillance information system, and consultation with experts. The incremental cost-effectiveness ratio (ICER) of BR vs. CR was determined. RESULTS: BR ( vs. CR) had a higher sputum culture conversion rate and cure rate and prevented many premature deaths (decreased by 12.8%), thereby obtaining more quality-adjusted life years (QALYs) (increased by 2.31 years). The per capita cost in BR was as high as 138,000 yuan, roughly double that of CR. The ICER for BR was 33,700 yuan/QALY, which was lower than China's 1× per capita Gross Domestic Product (GDP) in 2020 (72,400 yuan). CONCLUSION BR is shown to be cost effective. When the unit price of Bedaquiline reaches or falls below 57.21 yuan per unit, BR is expected to be the dominant strategy in China over CR.
Adult ; Humans ; Antitubercular Agents/therapeutic use* ; Cost-Effectiveness Analysis ; Cost-Benefit Analysis ; Tuberculosis, Multidrug-Resistant/drug therapy* ; China/epidemiology*

Objective: To understand the population structure of food-borne Staphylococcus (S.) aureus in China. Methods: Whole genome sequencing was used to analyze 763 food-borne S. aureus strains from 16 provinces in China from 2006 to 2020. Multilocus sequence typing (MLST), staphylococcal protein A gene (spa) typing, and staphylococcal chromosome cassettemec (SCCmec) typing were conducted, and minimum spanning tree based on ST types (STs) was constructed by BioNumerics 7.5 software. Thirty-one S. aureus strains isolated from imported food products were also included in constructing the genome phylogenetic tree. Results: A total of 90 STs (20 novel types) and 160 spa types were detected in the 763 S. aureus isolates. The 72 STs (72/90, 80.0%) were related to 22 clone complexes. The predominant clone complexes were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, accounting for 82.44% (629/763) of the total. The STs and spa types in the predominant clone complexes changed over the years. The methicillin-resistant S. aureus (MRSA) detection rate was 7.60%, and 7 SCCmec types were identified. The ST59-t437-Ⅳa (17.24%, 10/58), ST239-t030-Ⅲ (12.07%, 7/58), ST59-t437-Ⅴb (8.62%, 5/58), ST338-t437-Ⅴb (6.90%, 4/58) and ST338-t441-Ⅴb (6.90%, 4/58) were the main types in MRSA strains. The genome phylogenetic tree had two clades, and the strains with the same CC, ST, and spa types clustered together. All CC7 methicillin sensitive S. aureus strains were included in Clade1, while 21 clone complexes and all MRSA strains were in Clade2. The MRSA strains clustered according to the SCCmec and STs. The strains from imported food products in CC398, CC7, CC30, CC12, and CC188 had far distances from Chinese strains in the tree. Conclusions: In this study, the predominant clone complexes of food-borne strains were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, which overlapped with the previously reported clone complexes of hospital and community-associated strains in China, suggesting that close attention needs to be paid to food, a vehicle of pathogen transmission in community and food poisoning.
Humans ; Staphylococcus aureus/genetics* ; Methicillin-Resistant Staphylococcus aureus/genetics* ; Multilocus Sequence Typing ; Phylogeny ; Staphylococcal Infections/epidemiology* ; China/epidemiology*

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Objective: To analyze the association of No.11p posterior lymph node metastasis with clinicopathological features and its prognostic significance in gastric cancer. Methods: A single-center retrospective cohort study was conducted. Clinicopathological data of patients with primary gastric cancers undergoing No.11p posterior lymph node dissection from January 2016 to December 2020 were retrieved from the Database of Gastric Cancer, West China Hospital, Sichuan University. Case inclusion criteria: (1) gastric cancer proved by pathology; (2) radical resection with intraoperative No.11p posterior lymph node dissection; (3) operations performed by the same surgical team; (4) no previous history of other malignant tumors and no concurrent malignant tumors. Those with stump gastric cancer, history of gastrectomy, neoadjuvant chemotherapy, incomplete clinicopathological data and lost to follow-up were excluded. During the operation, the upper edge of the pancreas was retracted forward to expose the area between the upper edge of the pancreas and the splenic vessels. The proximal segment of the splenic artery was skeletonized to remove lymphatic tissue anterior and superior to the splenic artery for No.11p lymph node dissection. For patients with lymphadenopathy in the area between the splenic artery and the splenic vein, dissection was performed. The enlarged lymph nodes were labeled with titanium clips and named as No.11p posterior lymph node. Pathological examination was performed separately after the specimen was isolated. Statistical analysis was performed using R software. Results: A total of 127 gastric cancer patients, who underwent No.11p posterior lymph nodes dissection were included in this study, of which 120 patients without No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes negative) and 7 patients with No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes positive). A total of 8 metastatic No.11p posterior lymph nodes were detected in 7 patients, metastasis rate and with a ratio of 5.5% (7/127) and 6.8% (8/127), respectively. In the subgroup analysis of T3-4 stage patients, the metastasis rate and ratio of No.11p posterior lymph nodes were 9.0% (7/78) and 10.7% (8/75), respectively. Compared to negative cases, patients with No.11p posterior lymph nodes metastasis had larger tumor (P=0.002), higher proportion of Borrmann type Ⅲ and Ⅳ tumors (P=0.005), more metastatic lymph nodes (P<0.001), more advanced T stage (P=0.043), N stage (P=0.004) and TNM stage (P=0.015). In survival analysis, patients with No.11p posterior lymph node metastasis had a significantly worse prognosis than those without metastasis after adjusting for TNM stage (hazard ratio=3.009, 95% confidence interval: 1.824-4.964, P<0.001). Conclusions: The No.11p posterior lymph node metastasis in gastric cancer is associated with worse prognosis. For patients of T3-4 stage gastric cancer, No.11p posterior lymph node dissection should be emphasized during radical operation.
Gastrectomy ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology* ; Lymphatic Metastasis/pathology* ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/pathology*

OBJECTIVES: To study the cooling reaction kinetic characteristics of the temperature difference between cadaver temperature and ambient temperature (hereinafter referred to as "cadaver temperature difference") according to the reaction kinetics method. METHODS: Thirty rabbits were randomly divided into 5 groups with 6 rabbits in each group. The rabbits were injected with 10% potassium chloride solution intravenously. After death, the rabbits were placed at 5 ℃, 10 ℃, 15 ℃, 20 ℃ and 25 ℃ environment condition, respectively, and the rectal temperature was measured every minute for 20 hours. The measured cadaver temperature was subtracted from ambient temperature, and the cadaver temperature difference data was calculated using the reaction kinetics formula. The linear regression equation was fitted for analysis, and the experimental results were applied to the temperature difference data of human body after death for verification. RESULTS: Under different environmental conditions, the linear coefficient determination of temperature difference -ln(C/C₀) in rabbits was 0.99, showing a good linear relationship with time t. The application of human body temperature data after death was consistent with the results of animal experiments. CONCLUSIONS Under stable conditions, the temperature difference cooling process after death in rabbits is a first-order kinetic response. The method can also be used to study the temperature difference in human body after death.
Animals ; Humans ; Rabbits ; Body Temperature ; Temperature ; Kinetics ; Cadaver

OBJECTIVE: To compare the clinical efficacy of distal radius T-plate combined with suture anchor and distal clavicle anatomical locking plate combined with suture anchor in the treatment of Neer Ⅱb distal clavicle fracture. METHODS: From June 2014 to June 2018, 42 patients with Neer Ⅱb distal clavicle fractures were retrospectively analyzed. According to different surgical methods, they were divided into the observation group (T-shaped plate combined with suture anchor) and the control group (anatomical locking plate combined with suture anchor). There were 22 patients in the observation group and 20 patients in the control group. In the observation group, there were 13 males and 9 females, aged from 22 to 70 (45.78± 14.44) years old, 12 cases on the left side and 10 cases on the right side, 8 cases of traffic accident injury and 14 cases of fall. In the control group, there were 12 males and 8 females, aged from 24 to 66 (44.17±15.58) years, 13 cases on the left side and 7 cases on the right side, 6 cases of traffic accident injuryand 14 cases of fall. The operation time, intraoperative blood loss and fracture healing time were compared between the two groups, and Constant Murley score was used to evaluate shoulder joint function. RESULTS: The patients in both groups were followed up for 18 to 24 (20.96±2.02) months. The incisions of both groups were healed at stageⅠ. The fracture ends of both groups were bony healed at the last follow up. There was no significant difference in operation time, intraoperative blood loss and fracture healing time between two groups ( CONCLUSION The two methods can obtain satisfactory results in the treatment of Neer Ⅱb distal clavicle fractures, especially suitable for patients with comminuted distal clavicle fractures or osteoporosis; the clinical effect of the treatment of NeerⅡb distal clavicle fractures with T type distal radius plate combined with suture anchor is satisfactory, which provides another feasible treatment scheme for clinic.
Aged ; Aged, 80 and over ; Bone Plates ; Case-Control Studies ; Clavicle/surgery* ; Female ; Fracture Fixation, Internal ; Fractures, Bone/surgery* ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Suture Anchors ; Treatment Outcome

Aim To establish subcutaneous and orthotopic transplantation models of human lung cancer in nude mice, and compare the anti-cancer effects of digoxin between the two models. Methods After subcutaneous inoculation of H460 tissues in nude mice, the tumor volume was measured; HE staining and immunohistochemistry were performed; H460-Luc cell suspension was injected into the lung of nude mice toestablish orthotopic tumor model, the in vivo imaging and fluorescence values were recorded, and the tumor lesions in other organs were observed after dissection. Results Compared with control group, the gemcitabine group had a significant anti-tumor effect (P <0.05), and digoxin groups had no significant difference (P > 0.05). HE staining showed that the cell density in each treatment group decreased, and necrosis and/or fibrous hyperplasia were obvious. Immunohistochemistry indicated that the protein expression of p-p38, p-ERK and Nur77 in each treatment group significantly increased in the subcutaneous transplantation model; in the orthotopic transplantation model, the gemcitabine, the middle (P < 0.05) and low dose of digoxin group could inhibit the tumor growth, while the high dose of digoxin group accelerated the development of tumor (P < 0.05). Conclusion Digoxin is more sensitive to orthotopic transplanted tumor than subcutaneous transplanted tumor, anddigoxin may inhibit the tumor growth by up-regulating the expression of p-p38, pERK and Nur77.

BACKGROUND: Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) poses distinct clinical challenges due to extensively drug resistant (XDR) phenotype, and sequence type (ST) 11 is the most dominant blaKPC-2-bearing CP-Kp clone in China. The purpose of this current retrospective study was to explore the genetic factors associated with the success of XDR CP-Kp ST11 strains circulated in the intensive care unit (ICU) of a Chinese tertiary hospital. METHODS: Six ST11 XDR CP-Kp strains were identified between May and December 2014 and validated by minimum inhibitory concentration examination, polymerase chain reaction, and pyrosequencing. The six ST11 XDR CP-Kp, as well as three multi-drug resistant (MDR) and four susceptible strains, were sequenced using single-molecule real-time method. Comprehensively structural and functional analysis based on comparative genomics was performed to identify genomic characteristics of the XDR ST11 CP-Kp strains. RESULTS: We found that ST11 XDR blaKPC-2-bearing CP-Kp strains isolated from inpatients spread in the ICU of the hospital. Functionally, genes associated with information storage and processing of the ST11 XDR CP-Kp strains were more abundant than those of MDR and susceptible strains, especially genes correlative with mobile genetic elements (MGEs) such as transposons and prophages. Structurally, eleven large-scale genetic regions taken for the unique genome in these ST11 XDR CP-Kp strains were identified as MGEs including transposons, integrons, prophages, genomic islands, and integrative and conjugative elements. Three of them were located on plasmids and eight on chromosomes; five of them were with antimicrobial resistance genes and eight with adaptation associated genes. Notably, a new blaKPC-2-bearing ΔΔTn1721-blaKPC-2 transposon, probably transposed and truncated from ΔTn1721-blaKPC-2 by IS903D and ISKpn8, was identified in all six ST11 XDR CP-Kp strains. CONCLUSION Our findings suggested that together with clonal spread, MGEs identified uniquely in the ST11 XDR CP-Kp strains might contribute to their formidable adaptability, which facilitated their widespread dissemination in hospital.
Anti-Bacterial Agents ; Bacterial Proteins ; China ; Electrophoresis, Gel, Pulsed-Field ; Hospitals ; Humans ; Klebsiella Infections/drug therapy* ; Klebsiella pneumoniae/genetics* ; Microbial Sensitivity Tests ; Multilocus Sequence Typing ; Pharmaceutical Preparations ; Retrospective Studies ; beta-Lactamases/genetics*