AIM To explore the effect of Heidihuang Pills on renal fibrosis in a rat model of chronic renal failure(CRF)and its mechanism.METHODS Wistar rats were randomly divided into the blank group for normal feeding and the model group for the establishment of CRF rat models by 5/6 nephrectomy.Subsequently,the successfully established rat models were randomly divided into the model group,the Heidihuang Pills group(10.43 g/kg),and the Heidihuang Pills+IGF-1R blocker(JB1)group for a regimen of 7-day subcutaneous injection of 18 μg/kg JB1 followed by gavage of 10.43 g/kg Heidihuang Pills.Eight weeks after the administration,the rats had their serum levels of Scr and BUN detected;their pathological changes of renal tissue observed by HE and Masson staining;their renal protein expressions of TGF-β,HIF-1α and α-SMA detected by immunohistochemistry;their renal protein expressions of IGF-1R and TGF-β detected by Western blot;and their renal mRNA expressions of IGF-1R and TGF-β detected by RT-qPCR.RESULTS Compared with the blank group,the model group displayed increased serum levels of Scr and BUN(P＜0.05);increased,degree of renal fibrosis,and renal fibrosis area(P＜0.05);increased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P＜0.05);and decreased expressions of IGF-1R mRNA and protein(P＜0.05).Compared with the model group,the Heidihuang Pills group displayed decreased serum Scr and BUN levels(P＜0.05);decreased inflammatory cells in renal interstitium and the fibrosis degree(P＜0.05);decreased renal expressions of TGF-β,HIF-1α,α-SMA proteins and TGF-β mRNA(P＜0.05);and increased expressions of IGF-1R mRNA and protein(P＜0.05).However,the administration of JB1 could weaken the improvement effect of Heidihuang Pills on renal fibrosis in CRF rats(P＜0.05).CONCLUSION Heidihuang Pills can inhibit the renal fibrosis in CRF rats,and the inhibition process is related to up-regulated IGF-1 expression and promoted combination of IGF-1 and IGF-1R.

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.
Humans ; Bacteremia/epidemiology* ; Cefoperazone ; Sulbactam ; Retrospective Studies ; Drug Resistance, Bacterial ; Microbial Sensitivity Tests ; Hematologic Neoplasms ; Sepsis ; Anti-Bacterial Agents/pharmacology* ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Piperacillin, Tazobactam Drug Combination ; Escherichia coli

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cytarabine/therapeutic use* ; Daunorubicin/therapeutic use* ; Female ; Homoharringtonine/therapeutic use* ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/genetics* ; Male ; Middle Aged ; Nuclear Proteins ; Prognosis ; Remission Induction ; Retrospective Studies ; Young Adult

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cyclophosphamide/therapeutic use* ; Cytarabine/therapeutic use* ; Hematopoietic Stem Cell Transplantation ; Humans ; Idarubicin/therapeutic use* ; Leukemia, Myeloid, Acute/drug therapy* ; Neutropenia ; Prospective Studies ; Recurrence ; Retrospective Studies

The present study developed an ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap composite mass spectrometry(UHPLC-QTRAP-MS) to simultaneously determine the content of potential active components in Scutellariae Barbatae Herba and also to provide a reference approach for screening out the differential quality control components among different batches of Scutellariae Barbatae Herba. Chromatographic separations were conducted on a Thermo Acclaim~(TM) RSLC 120 C_(18) column(3.0 mm×100 mm, 2.2 μm) in a gradient program. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile, and the column temperature was maintained at 40 ℃. The flow rate was 0.4 mL·min~(-1) and the injection volume was 2 μL. The targeted compounds were monitored in the multiple reaction monitoring(MRM) mode. The acquired data were processed by hierarchical cluster analysis(HCA) and partial least square discriminant analysis(PLS-DA). Sixteen compounds all showed good linear relationship within the corresponding linear ranges and the R~2 values were all higher than 0.993 2. The RSDs of precision, repeatability, and stability were less than or equal to 3.7%. Mean recovery rates were in the range of 95.67% and 104.8% with RSDs≤3.2%. According to HCA and PLS-DA, all samples were clustered into four categories. Scutellarin, acteoside, scutellarein, and scutebarbatine X(VIP>1) were considered as differential chemical markers in the four categories. In conclusion, the developed method can be used for the simulta-neous determination of the multiple components and quality control of Scutellariae Barbatae Herba.
Chemometrics ; Chromatography, High Pressure Liquid/methods* ; Chromatography, Liquid ; Scutellaria ; Tandem Mass Spectrometry/methods*

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Objective: To investigate the functional outcomes and postoperative complications of Cheng's GIRAFFE reconstruction after proximal gastrectomy. Methods: A descriptive case series study was conducted. Clinical data of 100 patients with adenocarcinoma of the esophagogastric junction who underwent Cheng's GIRAFFE reconstruction after proximal gastrectomy in Cancer Hospital of University of Chinese Academy of Sciences (64 cases), Zhejiang Provincial Hospital of Chinese Medicine (24 cases), Lishui Central Hospital (10 cases), Huzhou Central Hospital (1 case) and Ningbo Lihuili Hospital (1 case) from September 2017 to June 2021 were retrospectively analyzed. Of 100 patients, 64 were males and 36 were females; the mean age was (61.3 ± 11.1) years and the BMI was (22.7±11.1) kg/m(2). For TNM stage, 68 patients were stage IA, 24 were stage IIA and 8 were stage IIB. Postoperative functional results and postoperative complications of radical gastrectomy with Giraffe reconstruction were analyzed and summarized. Gastroesophageal reflux disease questionnaire (RDQ) score and postoperative endoscopy were used to evaluate the occurrence of reflux esophagitis and its grade (grade N, grade A, grade B, grade C, and grade D from mild to severe reflux). The continuous data conforming to normal distribution were expressed as (mean ± standard deviation), and those with skewed distribution were presented as median (Q1, Q3). Results: All the 100 patients successfully completed R0 resection, including 77 patients undergoing laparoscopic surgery and 23 patients undergoing laparotomy. The Giraffe anastomosis time was (38.6±14.0) min; the blood loss was (73.0±18.4) ml; the postoperative hospital stay was 9.5 (8.2, 13.0) d; the hospitalization cost was (6.0±0.3) ten thousand yuan. Fourteen cases developed perioperative complications (14.0%), including 7 cases of pleural effusion or pneumonia, 3 cases of anastomotic leakage, 2 cases of gastric emptying disorder, 1 case of gastrointestinal hemorrhage and 1 case of anastomotic stenosis, who were all improved and discharged after symptomatic management. Patients were followed up for (33.3±1.6) months. Eight patients were found to have reflux symptoms by RDQ scale six months after surgery, and 11 patients (11/100,11.0%) were found to have reflux esophagitis by gastroscopy, including 6 in grade A, 3 in grade B, and 2 in grade C. All the patients could control their reflux symptoms with behavioral guidance or oral PPIs. Conclusion: Cheng's GIRAFFE reconstruction has good anti-reflux efficacy and gastric emptying function; it can be one of the choices of reconstruction methods after proximal gastrectomy.
Adenocarcinoma/surgery* ; Aged ; Esophageal Neoplasms/surgery* ; Esophagitis, Peptic/etiology* ; Esophagogastric Junction/surgery* ; Female ; Gastrectomy/methods* ; Gastroesophageal Reflux/etiology* ; Humans ; Laparoscopy ; Male ; Middle Aged ; Reconstructive Surgical Procedures/methods* ; Recovery of Function ; Retrospective Studies ; Stomach Neoplasms/surgery*

OBJECTIVE: To investigate the down-regulation of ANRIL (Antisense non-coding RNA in the INK4 Locus) effects on proliferation and apoptosis of Kasumi-1 cells and its related molecular mechanism. METHODS: Recombinant lentivirus was used to construct ANRIL down-regulation Kasumi-1 cells (sh-ANRIL group) and its control cells (sh-NC group). A fluorescence microscope was used to observe the transfection efficiency, RT-qPCR was used to detect knockdown efficiency and ANRIL expression in PBMCs and MBMCs of patients with acute myeloid leukemia (AML). Proliferation and apoptosis of Kasumi-1 cells were assayed by CCK-8 method and flow cytometry. Western blot was employed to detect the expression of PI3K, AKT, p-AKT, and relevant protein after down-regulation of ANRIL in Kasumi-1 cells. RESULTS: ANRIL overexpressed significantly in PBMCs and MBMCs of patients with AML, the transfection efficiency of recombinant lentivirus carrying sh-ANRIL and sh-NC on Kasumi-1 cells exceeded 90%, and the knockdown efficiency was 70%. When DNR was administrated for 24, 48, and 72 hours, the cell inhibition rate of the sh-ANRIL group was (47.40±1.49)%, (69.11±0.51)% and (91.82±1.10)%, which were significantly higher than those of the sh-NC group, respectively (P<0.05). The apoptotic rate in the sh-ANRIL group was (10.29±0.58)%, which was significantly higher than (5.42±0.67)% of the sh-NC group (P<0.01). After DNR treatment for 24 hours, the apoptotic rate of the sh-ANRIL group was (54.41±1.69)%, which was significantly higher than (38.28±1.42)% of sh-NC group (P<0.001). Western blot revealed that the protein levels of PI3K, p-AKT, PCNA, and BCL-2 in the sh-ANRIL group were reduced significantly than those in the sh-NC group, while the BAX protein expression increased. CONCLUSION ANRIL may affect the proliferation and apoptosis of Kasumi-1 cells through PI3K/AKT signaling pathway. ANRIL is a potential therapeutic target for AML.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; RNA, Long Noncoding/genetics*