Cocrystal separation technology is a technology that utilizes coformers to selectively form cocrystals with target compounds and separate them from mixed systems. Our study used puerarin (PUE), daidzein (DDZ), and genistein (GEN) as model drugs, which have similar structures and are the main isoflavones in Pueraria lobata root. The separation and purification processes in the modern traditional Chinese medicine (TCM) of these three components use conventional column chromatography, recrystallization, and other technologies, which have the issues of lengthy separation cycles, high solvent consumption, and inefficient preparation. Different with existing separation technology, our team used the early-found cocrystal separation method to design a step-by-step extraction and separation experiment of GEN-PUE-DDZ ternary mixture. Caffeine and L-proline were added to the mixed system in turn, GEN-caffeine cocrystal and PUE-proline cocrystal were prepared by suspension method. The cocrystals precipitated out of the solution. The purities of the GEN-caffeine cocrystal and the PUE-proline cocrystal could achieve 93% (the purity of GEN) and 99% (the purity of PUE). Besides, the purity of DDZ could also be increased by 6.76 times. This study proposed a simple operating, low cost and wide application range separation method different from the traditional separation method and realized the separation of structurally similar chemical components in TCM, laying a foundation for the application of cocrystal technology in the separation and refining of TCM.

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 analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ² test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia/epidemiology* ; Blood Transfusion ; Female ; Gastrointestinal Neoplasms/surgery* ; Humans ; Length of Stay ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Animals ; Carbon Tetrachloride ; Drugs, Chinese Herbal/therapeutic use* ; Ethanol ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Rats ; Rats, Sprague-Dawley

Objective:To explore the relationship between somatic symptoms of major depressive disorder(MDD)and cortisol(COR) rhythm, C-reactive protein(CRP) and other immune-metabolism-related indicators, and understand its mechanism from the perspective of endocrine and immune regulation.Methods:A case-control study was conducted in hospitalized patients with MDD who met DSM-5 diagnostic criteria.According to the Patient Health Questionnaire (PHQ-15), PHQ-15 ≥10 were classified as the somatic major depressive disorder group(S-MDD group) and 73 patients were enrolled.PHQ-15 <5 was classified as the non-somatic depressive disorder group (NS-MDD group) and 70 patients were enrolled.Plasma cortisol (COR8, COR16 and COR24) levels were measured at 8∶00, 16∶00 and 24∶00 on the same day, plasma CRP and interleukin-6 (IL-6) level, serum uric acid (UA), blood glucose (GLU), blood lipid (TC, TG, HDL, LDL) level were detected at 8∶00.Independent sample t test, non-parametric test, chi-square test, repeated ANOVA, covariance analysis, and multivariate Logistic regression were used for statistical analysis. Results:①Time effect, grouping effect and the interaction effect of the time and grouping in the level of COR were statistically significant ( P<0.05). Covariance analysis excluded age as an influential factor, COR16, AUC(total cortisol output/area under the curve, AUC) and COR8-16 in S-MDD group ((90.50±40.57)μg/L, (1 425.12±564.78), (-6.43±5.76))were higher than those in NS-MDD group((68.74±31.51)μg/L, (1 251.57±456.61), (-8.77±5.48)), and the difference was statistically significant ( F=8.971, 4.320, 8.731, P<0.05). ②CRP in S-MDD group ((1.41±1.06)mg/L) were higher than that in NS-MDD group((0.61±0.53)mg/L), and the difference was statistically significant ( F=25.436, P<0.05). The proportion of patients with higher CRP level(CRP≥1 mg/L) in S-MDD group(58%) was higher than that in NS-MDD group(23%), and the difference was statistically significant(χ 2=17.824, P<0.01). ③Multivariate logistic regression analysis found that CRP ( OR=4.953, 95% CI: 2.407-10.193), COR8-16 ( OR=3.451, 95% CI: 1.380-8.633) were main risk factors of somatic symptoms of MDD ( P<0.05). Conclusion:Cortisol rhythm disturbance and high CRP level may be the biological basis of somatic symptoms in patients with MDD.

Objective: To investigate the effect of argatroban in repair of spinal cord injury in rats. Methods: A total of 54 female Wistar rats were selected and divided into three groups according to the random number table: sham group, injury group and Argatroban group, with 18 rats in each group. The sham group only took the T₁₀lamina; the injury group used the spinal cord injury device to make the rat spinal cord injury model; the Argatroban group received Argatroban treatment after spinal cord injury. The recovery of hindlimb motor function was evaluated by BBB score and clined plate test before injury and 7, 14, 21, 28, 35 and 42 days after injury. The sensory evoked potentials (SEP) and motor evoked potentials (MEP) were detected 42 days after operation. HE staining was used to compare the size of the cavity in the local region 42 days after injury. Results: At day 7 after injury, the BBB score was (3.7±0.5)points and the inclined plane test was (28.0±2.6)° in the Argatroban group, which were better than those in the injury group [(3.3±0.5)points, (24.3±1.9)°] (P<0.05). At day 42 after injury, the BBB score was (13.0±0.8)points and inclined plane test was (50.7±2.7)° in the Argatroban group, which were significantly better than those in the injury group [(9.7±1.3) points, (40.5±2.7)°] (P<0.05). But all the above values in the Argatroban group were significantly lower than those in the sham group [(21.0±0.0)points, (60.0±0.0)°](P<0.05). At day 42 after operation, the SEP latency [(25.0±0.9)ms] in the Argatroban group was significantly shorter than that in the injury group [(31.5±1.9) ms]; the amplitude [(2.1±0.1)μV] in the Argatroban group was lower than that in the injury group [(0.5±0.1)μV] (P<0.05). The MEP latency [(11.5±1.0)ms] in the Argatroban group was significantly shorter than that in the injury group [(17.5±1.1)ms], and the amplitude [(4.8±0.8)μV] in the Argatroban group was lower than that in the injury group [(2.8±0.7)μV] (P<0.05). And the SEP or MEP latency and amplitude in the Argatroban group showed significant differences compared to the sham group [(7.5±1.0)ms, (7.5±1.0)μV](P<0.05). HE staining showed that the central area of the lesion in the Argatroban group [(0.35±0.04)mm²] was significantly smaller than that in the injury group [(0.71±0.05)mm²]. Conclusion After spinal cord injury, argatroban can protect the spinal cord tissue effectively in the injured area and promote recovery of sensory and motor function in the hind limbs of rats.

OBJECTIVE: To study role of TLR4/NF-κB pathway for early change of synovial membrane in knee osteoarthritis rats. METHODS: Eighteen male SD rats weighted (200±20) g were randomly divided into 2 groups, namely control and model group, and 9 in each group. Knee OA model group was established by using modified Hulth method in model group. Control group was not treated. Synovial tissue and serum was extracted at 4 and 21 d after operation. Expression of CD14, TLR4, IL-1β, TNF-α, ADAMTS-4, MMP-13 were detected by real-time PCR respectively. NF-κB p65 protein was detected by Western-blot; serum concentrations of haluronic acid (HA), N-propeptide of type III procollagen(PIIINP) was detected by Elisa. RESULTS: Expression of CD14, ADAMTS-4, and NF-κB p65 in model group were higher than that of control group at 4 and 21 days after operation, while expression of TLR4, IL-1β, TNF-α and MMP-13 were higher than that of control group at 21 days after operation(<0.01). Concentration of PIIINP and HA in model group were higher than that of control group at 4 days after operation, while there was no significant difference at 21 days after operation. CONCLUSIONS NF-κB pathway could mediate occurrence of KOA by early activating and triggeringg synovial increasingly secreting inflammatory secretion CD14, TLR4, IL-1β, TNF-α, ADAMTS-4, MMP-13, PIIINP and HA.
Animals ; Male ; NF-kappa B ; Osteoarthritis, Knee ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Synovial Membrane ; Toll-Like Receptor 4

Objective To understand the prevalence of small for gestational age (SGA) in Zhuang population, and to analyze the potential factors of SGA. Methods A total of 3 839 live births in the Wuming District People’s Hospital and Wuming Maternal and Child Health Hospital from January 2016 to January 2018 were recruited. Random Forest, 2 test and Logistic regression model were used for statistical analyses. Results The incidence of SGA was 9.6% (368/3 839), and it was 6.9% (142/2 049) and 12.6% (226/1 790) for male and female infants respectively. Random Forest method showed that second-trimester intrauterine growth restriction’s importance score was the highest, but gestational week’s was the lowest. Also, seven important variables were selected by this method. Unconditional logistic regression analysis showed that parity <2, the height of mothers <1.55 m, insufficient gestational weight gain, second-trimester intrauterine growth restriction were risk factors for SGA, but pre-pregnancy BMI ≥18.5 kg/m2 and male infants were protective factors. Conclusions The incidence of SGA is slightly higher, among the Zhuang population in Guangxi. SGA is affected by many factors. Therefore, it is necessary to evaluate the status of intrauterine growth and adopt comprehensive measures to control and reduce the incidence of SGA.

Objective To investigate the value of support vector machine based MRI-radiomics in the differential diagnosis of primary hepatic carcinomas (PHCs). Methods PHCs patients were retrospectively collected from July 2013 to February 2017 in the First Affiliated Hospital of Zhejiang University.All patients underwent unenhanced and enhanced MRI liver scan before surgery,and confirmed by pathology. A total of 294 PHCs patients (305 lesions), including 96 cases (97 lesions) of massive type cholangiocarcinoma (mCC), 107(107 lesions)of hepatocellular carcinoma (HCC), and 91 (101 lesions) of mixed hepatocellular and cholangiocellular carcinomas(HCC-CC).All patients underwent unenhanced and dynamic enhanced MRI liver scan including arterial, portal venous and equilibrium phases. Two hundred and three lesions (65 mCC, 71 HCC, 67 HCC-CC) were assigned into the training set, the remaining 102 lesions(32 mCC,36 HCC,34 HCC-CC)into the validation set,according to a ratio of 2:1.The entire lesions were delineated manually using a region of interest on equilibrium phase of enhanced MRI by using a home-made dedicated software(Analysis Kit,AK,General Electrics,US).Then the least absolute shrinkage and selection operator (LASSO) regression was used to select image features with a method of 10 fold cross-validation, and to reduce the dimensionality. The spearman method was used afterwards to condense the image features by removing redundant.A predictive model of diagnosing the different types of PHCs was established based on support vector machines(SVM),and the accuracy of applying the model in the data sets was used to evaluate the diagnostic efficacy of the model. Results A total of 280 quantitative imaging features were extracted in the training set.Thirty one imaging features were selected after LASSO regression and dimensionality reduction,and 21 features were remained after redundancy removing.The SVM showed the best generalization ability when the first 11 imaging features were used due to the Hughes effect.The 11 imaging features include 4 parameters of histogram,2 of textures,4 of gray-level co-occurrence matrix and 1 of gray-level run length matrix. A predictive model for PHCs was established after the study of the 11 imaging features and a regression analysis using SVM.The accuracy of the predictive model was 80.3% (163/203) in differentiating PHCs in the training set. The accuracy of the model was 75.5% (77/102) after applying it in the validation set. The diagnostic accuracy for HCC-CC, HCC and mCC was 85.3% (29/34), 77.8% (28/36) and 62.5% (20/32), respectively, in the validation set. For HCC-CC, 3 cases were misdiagnosed as mCC and 2 cases as HCC.For HCC,3 cases were misdiagnosed as HCC-CC and 5 cases as mCC.For mCC,9 cases were misdiagnosed as HCC-CC and 3 cases as HCC.The model showed the highest accuracy in predicting HCC-CC.Conclusion Radiomics method based on SVM may have a high accuracy in predicting different pathologic types of PHC,with the highest accuracy for HCC-CC.