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 analyze the atrioventricular synchronization rate after implantation of Micra AV leadless pacemaker,and the impact of postoperative programming optimization on atrioventricular synchronization rate.Methods A prospective cohort study was conducted to select patients with complete atrioventricular block who underwent Micra AV leadless pacemaker implantation at Beijing Anzhen Hospital from August 2022 to June 2023.Programming optimization were performed at 1 week,1 month,and 3 months postoperatively,and atrioventricular synchronization rate,electrical parameters,and echocardiography were recorded.Results A total of 68 patients with complete atrioventricular block implanted with Micra AV were selected,with an average age of(68.2±9.7)years,including 47 males(69.1％).All patients were successfully implanted with Micra AV,and there were no serious postoperative complications;The average threshold,sense,and impedance parameters were stable during 1 week,1 month,and 3 months after the procedure;There was no significant difference in the EF value of postoperative echocardiography(P=0.162);The average atrioventricular synchronization rates at 1 week,1 month,and 3 months postoperatively were(75.2％vs.83.8％vs.91.6％,P=0.001).Conclusions As an mechanical atrial sensing,Micra AV requires personalized adjustment of relevant parameters;Postoperative follow-up programming optimization plays an important role in the atrioventricular synchronization and comfort level in patients with complete atrioventricular block after implantation of Micra AV leadless pacemaker.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Purpose::The reconstruction of Allen's type IV fingertip amputation is a clinical challenge. Our team designed bilateral unequal-sized hallux osteo-onychocutaneous free flaps for the long-term reconstruction of Allen's type IV fingertip amputation and conducted a retrospective study with a 5-year follow-up aims to evaluate the effects of this technique.Methods::A retrospective analysis with a 5-year follow-up including 13 patients with Allen's type IV fingertip amputation who were admitted to our hospital from January 2010 to January 2017 was conducted. The patients were treated with bilateral unequal-sized hallux osteo-onychocutaneous free flaps. The operation time, intraoperative blood loss, and complications were recorded, and the survival rate of the transplanted flaps was calculated. During the 5-year follow-up after operation, the nail growth time was recorded and the finger appearance was observed. At the last follow-up appointment, the length, width, and girth of the reconstructed fingertip and contralateral normal fingertip, range of motion of the reconstructed fingertip and contralateral normal fingertip, Semmes-Weinstein test (for the evaluation of tactile sensation), and two-point discrimination testing results were recorded. SPSS 22.0 software was used for the statistical analysis and the data are presented as mean ± SD.Results::The mean operation time was (5.62 ± 0.51) h, the mean intraoperative blood loss was (34.15 ± 3.13) mL, and the survival rate of the transplanted flaps was 100%. During the 5-year follow-up, the average nail growth time was (10.14 ± 1.98) months and the average bone union time was (3.78 ± 0.91) months. The length, width, and girth of the reconstructed fingertip were (31.52 ± 3.73) mm, (17.82 ± 1.74) mm, and (59.75 ± 3.04) mm, respectively, which did not differ from those of the contralateral normal fingertip. The range of motion of the reconstructed fingertip was (12.15 ± 2.79) degrees which is different from that of the contralateral normal fingertip. The average tactile sensation evaluated via the Semmes-Weinstein test and the average two-point discrimination test of the reconstructed fingertip were (0.39 ± 0.17) g and (7.46 ± 1.14) mm, respectively, which were not different from those of the contralateral normal fingertip. The average Maryland score of feet in the donor area was 87.66 ± 7.39, which was satisfactory.Conclusion::Bilateral unequal-sized hallux osteo-onychocutaneous free flaps are an effective method to reconstruct Allen's type IV fingertip amputations with a satisfactory appearance and good sensory function.

Objective To investigate the clinical efficacy of therapy of clearing heat,percolating dampness and lowering turbidity combined with Silibin Meglumine Tablets in the treatment of non-alcoholic steatohepatitis(NASH)patients with abnormal alanine aminotransferase(ALT)level of damp-heat accumulation type.Methods A retrospective study was conducted.According to the medication,80 patients with NASH with abnormal ALT level of damp-heat accumulation type were divided into control group and observation group,with 40 cases in each group.The control group was treated with Silibin Meglumine Tablets,and the observation group was treated with therapy of clearing heat,percolating dampness and lowering turbidity on the basis of treatment for the control group.The course of treatment covered 12 weeks.The changes of liver function indicators of ALT,aspartate aminotransferase(AST),and gamma glutamyl transpeptidase(GGT),blood lipid indicators of total cholesterol(CHOL)and triglyceride(TRIG),and the degree of hepatic steatosis in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 12 weeks of treatment,the total effective rate of the observation group was 95.00%(38/40),and that of the control group was 77.50%(31/40).The curative effect of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the levels of ALT,AST and GGT in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of ALT,AST and GGT in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the levels of CHOL and TRIG in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of CHOL and TRIG in the observation group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the degree of hepatic steatosis in the two groups was significantly lower than that before treatment(P＜0.05),and the decrease of the degree of hepatic steatosis in the observation group was significantly superior to that in the control group(P＜0.05).(5)During the treatment,no obvious adverse reactions occurred in the two groups,indicating high safety.Conclusion The therapy of clearing heat,percolating dampness and lowering turbidity combined with Silibin Meglumine Tablets exerts certain effect in the treatment of NASH patients with abnormal ALT level of damp-heat accumulation type,and the therapy can significantly enhance the clinical efficacy of Silibin Meglumine Tablets alone for NASH.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

This article aims to analyze the therapeutic effect and probe into the mechanism of Sanhuang Hushen Fangshuai Decoction in treating chronic kidney disease(CKD) based on metabolomics and bioinformatics. The patients with stage 3-4 CKD diagnosed and treated in the Changzhou Hospital of Traditional Chinese Medicine from June 2023 to March 2024 were enrolled in this study. The patients were treated with Sanhuang Hushen Fangshuai Decoction, and the therapeutic effect was evaluated. The serum samples were collected before and after treatment. Ultra-performance liquid chromatography was employed to detect metabolites in the serum, and multivariate statistical analysis was performed. Bioinformatics was employed to screen the active components and targets of the decoction and the potential targets of CKD. The protein-protein interaction(PPI) network of the common targets shared by the decoction and CKD and the drug-component-target network were constructed. The core components and targets were screened according to the correlation degree of the network. The binding between core components and targets was verified by molecular docking. The results showed that Sanhuang Hushen Fangshuai Decoction improved the renal function and reduced proteinuria. Compared with the healthy population, the post-treatment population showed recovery of 54 up-regulated metabolites and 43 down-regulated metabolites. Enrichment analysis results showed that the key pathways included adenosine triphosphate binding cassette(ABC) transport, tryptophan metabolism, and tyrosine metabolism. The results of bioinformatics analysis showed that the core components of Sanhuang Hushen Fangshuai Decoction in treating CKD included kaempferol, β-sitosterol, luteolin, 7-O-methylisolingol, and tanshinone Ⅱ_A. The core targets included TP53, PTGS2, JUN, AKT1, and TNF. Molecular docking results showed that the core components bound well to the target genes. The results of joint pathway analysis suggested that both differential metabolites and key targets were involved in galactose metabolism, nicotinamide metabolism, and other pathways. This study suggests that Sanhuang Hushen Fangshuai Decoction is effective for CKD, and it can regulate multiple abnormal metabolites and participates in multiple metabolic pathways involving amino acids and sugars. The active components such as kaempferol in the decoction may regulate related targets such as TP53 and PTGS2. This study provides a basis for the prevention and treatment of CKD with traditional Chinese medicine.
Drugs, Chinese Herbal/administration & dosage* ; Renal Insufficiency, Chronic/genetics* ; Humans ; Computational Biology ; Male ; Metabolomics ; Protein Interaction Maps/drug effects* ; Middle Aged ; Molecular Docking Simulation ; Female ; Adult ; Aged

Objective: To screen the key genes involved in gefitinib resistance of lung adenocarcinoma PC9/GR cells which harbored 19 exon mutation of epidermal growth factor receptor (EGFR) gene, and discuss the effect and mechanism of downregulation of solute carrier family 7 member 11 (SLC7A11) on the gefitinib resistance of PC9/GR cells. Methods: RNA microarray was conducted to detect the gene expressions in PC9 and PC9/GR cells. The differently expressed genes were screened by using limma package of R language and analyzed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Western blotting was performed to determine the expression of SLC7A11 protein in PC9 and PC9/GR cells. PC9/GR cells were infected with lentivirus plasmid containing short hairpin RNA (shRNA) targeting SLC7A11 or negative control shRNA (sh-NC), respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the efficacy of shRNA on the expression of SLC7A11 mRNA. Cell counting kit-8 (CCK-8) assay was conducted to determine the suppressing effect of gefitinib on PC9/GR cells. Mito-Tracker Red CMXRos probe and malondialdehyde (MDA) assay kit were used to evaluate gefitinib-induced ferroptosis in PC9/GR cells. Immunohistochemistry (IHC) was conducted to detect the expression of SLC7A11 protein in the tumor tissues of advanced stage lung adenocarcinoma patients harboring 19 exon mutation of EGFR gene. Thirty-six advanced stage lung adenocarcinoma patients who received EGFR-tyrosihe kinase inhibitor(TKI) as first-line treatment in Fourth Hospital of Hebei Medical Unviersity were enrolled. Kaplan-Meier survival curve was drawn to analyze the correlation between SLC7A11 expression and progression-free survival (PFS) of the patients. Results: RNA array demonstrated that 2 888 genes were differently expressed between PC9 and PC9/GR cells. KEGG analysis showed that ferroptosis-related gene was one of the most enriched region of the differently expressed genes between PC9 and PC9/GR cells. These ferroptosis-related gene cohort contained 13 genes, among which SLC7A11 exhibited the most significant difference. Western blotting showed that the expression of SLC7A11 protein in PC9/GR cells was significantly higher than that in PC9 cells (0.76±0.03 vs. 0.19±0.02, P<0.001). The 50% inhibiting concentration (IC(50)) of gefitinib was 35.08 μmol/L and 64.01 μmol/L for sh-SLC7A11 and sh-NC group PC9/GR cells, respectively. PC9/GR cells in sh-SLC7A11 group exhibited significantly lower density of mitochondria fluorescence after gefitinib treatment, compared to the sh-NC group (213.77±26.50 vs. 47.88±4.55, P<0.001). In addition, PC9/GR cells in sh-SLC7A11 group exhibited significantly higher MDA after gefitinib treatment, compared to the sh-NC group [(15.43±1.60) μmol/mg vs. (82.18±7.77) μmol/mg, P<0.001]. The PFS of the patients with low expression of SLC7A11 (n=18) was significantly longer than the patients with high expression of SLC7A11 (n=18, 16.77 months vs. 9.14 months, P<0.001). Conclusion: Downregulation of SLC7A11 could increase the sensitivity of PC9/GR cells to gefitinib by promoting ferroptosis.
Humans ; Gefitinib/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Lung Neoplasms/pathology* ; Down-Regulation ; Quinazolines/therapeutic use* ; Drug Resistance, Neoplasm/genetics* ; ErbB Receptors/metabolism* ; Adenocarcinoma of Lung ; Protein Kinase Inhibitors/therapeutic use* ; RNA, Small Interfering/genetics* ; Cell Line, Tumor ; Amino Acid Transport System y+/metabolism*

Objective: To screen the key genes involved in gefitinib resistance of lung adenocarcinoma PC9/GR cells which harbored 19 exon mutation of epidermal growth factor receptor (EGFR) gene, and discuss the effect and mechanism of downregulation of solute carrier family 7 member 11 (SLC7A11) on the gefitinib resistance of PC9/GR cells. Methods: RNA microarray was conducted to detect the gene expressions in PC9 and PC9/GR cells. The differently expressed genes were screened by using limma package of R language and analyzed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Western blotting was performed to determine the expression of SLC7A11 protein in PC9 and PC9/GR cells. PC9/GR cells were infected with lentivirus plasmid containing short hairpin RNA (shRNA) targeting SLC7A11 or negative control shRNA (sh-NC), respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the efficacy of shRNA on the expression of SLC7A11 mRNA. Cell counting kit-8 (CCK-8) assay was conducted to determine the suppressing effect of gefitinib on PC9/GR cells. Mito-Tracker Red CMXRos probe and malondialdehyde (MDA) assay kit were used to evaluate gefitinib-induced ferroptosis in PC9/GR cells. Immunohistochemistry (IHC) was conducted to detect the expression of SLC7A11 protein in the tumor tissues of advanced stage lung adenocarcinoma patients harboring 19 exon mutation of EGFR gene. Thirty-six advanced stage lung adenocarcinoma patients who received EGFR-tyrosihe kinase inhibitor(TKI) as first-line treatment in Fourth Hospital of Hebei Medical Unviersity were enrolled. Kaplan-Meier survival curve was drawn to analyze the correlation between SLC7A11 expression and progression-free survival (PFS) of the patients. Results: RNA array demonstrated that 2 888 genes were differently expressed between PC9 and PC9/GR cells. KEGG analysis showed that ferroptosis-related gene was one of the most enriched region of the differently expressed genes between PC9 and PC9/GR cells. These ferroptosis-related gene cohort contained 13 genes, among which SLC7A11 exhibited the most significant difference. Western blotting showed that the expression of SLC7A11 protein in PC9/GR cells was significantly higher than that in PC9 cells (0.76±0.03 vs. 0.19±0.02, P<0.001). The 50% inhibiting concentration (IC(50)) of gefitinib was 35.08 μmol/L and 64.01 μmol/L for sh-SLC7A11 and sh-NC group PC9/GR cells, respectively. PC9/GR cells in sh-SLC7A11 group exhibited significantly lower density of mitochondria fluorescence after gefitinib treatment, compared to the sh-NC group (213.77±26.50 vs. 47.88±4.55, P<0.001). In addition, PC9/GR cells in sh-SLC7A11 group exhibited significantly higher MDA after gefitinib treatment, compared to the sh-NC group [(15.43±1.60) μmol/mg vs. (82.18±7.77) μmol/mg, P<0.001]. The PFS of the patients with low expression of SLC7A11 (n=18) was significantly longer than the patients with high expression of SLC7A11 (n=18, 16.77 months vs. 9.14 months, P<0.001). Conclusion: Downregulation of SLC7A11 could increase the sensitivity of PC9/GR cells to gefitinib by promoting ferroptosis.
Humans ; Gefitinib/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Lung Neoplasms/pathology* ; Down-Regulation ; Quinazolines/therapeutic use* ; Drug Resistance, Neoplasm/genetics* ; ErbB Receptors/metabolism* ; Adenocarcinoma of Lung ; Protein Kinase Inhibitors/therapeutic use* ; RNA, Small Interfering/genetics* ; Cell Line, Tumor ; Amino Acid Transport System y+/metabolism*

OBJECTIVE: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy. METHODS: The data of 67 LS-SCLC patients who received combined treatment of CM and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guang'anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan-Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. RESULTS: The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI: 12.357-25.643) vs. 9 months (95% CI: 5.957-12.043), HR=0.43 (95% CI: 0.27-0.69, P<0.001), respectively. The median OS in the CM and WM combination group and the WM group were 34 months (95% CI could not be calculated) vs. 18.63 months (95% CI: 16.425-20.835), HR=0.40 (95% CI: 0.24-0.66, P<0.001), respectively. Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months (P<0.001). CONCLUSION The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616).
Humans ; Small Cell Lung Carcinoma/drug therapy* ; Lung Neoplasms/drug therapy* ; Retrospective Studies ; Prognosis ; Combined Modality Therapy