OBJECTIVE: To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome. METHODS: In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded. RESULTS: From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05). CONCLUSION Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).
Humans ; Paroxetine/adverse effects* ; Spleen ; Anxiety ; Syndrome ; Medicine, Chinese Traditional ; Treatment Outcome ; Double-Blind Method

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.

Tweety-homolog 1 (Ttyh1) is expressed in neural tissue and has been implicated in the generation of several brain diseases. However, its functional significance in pain processing is not understood. By disrupting the gene encoding Ttyh1, we found a loss of Ttyh1 in nociceptors and their central terminals in Ttyh1-deficient mice, along with a reduction in nociceptor excitability and synaptic transmission at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) in the basal state. More importantly, the peripheral inflammation-evoked nociceptor hyperexcitability and spinal synaptic potentiation recorded in spinal-PAG projection neurons were compromised in Ttyh1-deficient mice. Analysis of the paired-pulse ratio and miniature excitatory postsynaptic currents indicated a role of presynaptic Ttyh1 from spinal nociceptor terminals in the regulation of neurotransmitter release. Interfering with Ttyh1 specifically in nociceptors produces a comparable pain relief. Thus, in this study we demonstrated that Ttyh1 is a critical determinant of acute nociception and pain sensitization caused by peripheral inflammation.

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

BACKGROUND: Traditional Chinese exercises (TCEs) have a positive effect on glycemic control and hemoglobin A1c (HbA1c), but there is no consensus on the benefits of TCEs for patients with prediabetes. OBJECTIVE: The objective of this study was to systematically investigate the effects of TCEs on blood glucose control in patients with prediabetes. SEARCH STRATEGY: Comprehensive retrieval of randomized controlled trials (RCTs) was carried out using PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Data Knowledge Service Platform, China Biology Medicine disc, Google Scholar and Baidu academic databases. The retrieval window ranged from the establishment of the database to December 2018, and references related to the included trials were searched without language restrictions. INCLUSION CRITERIA: The study included RCTs with a clinical diagnosis of prediabetes that was also treated with TCEs. DATA EXTRACTION AND ANALYSIS: Literature screening, data extraction and literature quality assessment were performed independently by two researchers. In the case of disagreement, a third party was invited to negotiate and make a decision. Standardized mean difference (SMD) was used to estimate the therapeutic effect. Meta-analysis was performed using Review Manager 5.3.5 and Stata 15.0. Heterogeneity was assessed using Q test and I, and the source of heterogeneity was determined using Galbraith diagram and sensitivity analysis. A Q test resulting in P < 0.1 and I > 50% indicated significant difference and random effect model analysis was performed. Otherwise, a fixed effect model was applied. Begg's and Egger's tests were used to assess publication bias. RESULTS: Nine RCTs involving 485 participants were included in this study. The results showed that TCEs could reduce fasting blood glucose (FBG), 2 h blood glucose (2hPBG) and HbA1c in patients with prediabetes. The treatment subgroup showed that an intervention of 6 months had better results, while the Gongfa subgroup showed that the TCE Baduanjin yielded better results. (1) FBG: SMD = -0.73, 95% confidence interval (CI) [-0.97, -0.50], P < 0.00001; Baduanjin: SMD = -0.83, 95% CI [-1.13, -0.53], P < 0.00001; 6 month treatment: SMD = -0.73, 95% CI [-1.20, -0.26], P = 0.002. (2) 2hPBG: SMD = -0.75, 95% CI [-0.94, -0.57], P < 0.00001; Baduanjin: SMD = -0.62, 95% CI [-0.91, -0.32], P < 0.00001; 6 month treatment: SMD = -0.91, 95% CI [-1.39, -0.44], P = 0.0002. (3) HbA1c: SMD = -0.56, 95% CI [-0.89, -0.23], P = 0.00008; Baduanjin: SMD = -0.46, 95% CI [-0.83, -0.08], P = 0.02; 6 month treatment: SMD = -0.77, 95% CI [-1.24, -0.29], P = 0.002. CONCLUSION TCEs had positive effects in improving blood glucose levels in patients with prediabetes. Hence, TCEs may be of potential therapeutic value for patients with prediabetes, as an adjuvant therapy along with other treatments. Although the evidence suggests that the intervention is effective for 6 months, the mechanism of TCEs on glycemic control, the minimum exercise dose and their safety remain to be further studied.

OBJECTIVE: To investigatc the curative efficacy of low dose rituximab for glucocorticoid ineffective on dependent ITP patients and its relation with sensitivity to glucocorticoid so as to provide reference basis for rational use of drugs in clinical treatmant. METHODS: Seventy-ninth ITP patients enrolled in this study included the glucocorticoid-ineffective patients (19 cases) and glucocorticoid-dependent patients (60 cases). All ITP patients were treated with regimen consisted of high dose dexamethasone plus low dose rituximab (dexal-methasone 40 mg/d for 4 days per os, ritaximab 100 mg by intravenous infusion at D7, 14, 21 and 28 respectively). The patients after treatment were followed-up for 12 month, and the relation of patients sensitivity to glucocorticoid with therapentic response of rituximab was analyzed. The changes of Treg cell ratio and BAFF, IL-2 and sCD40L levels before and after treatment were detected by flow cytometry and ELISA respectively. RESULTS: The overall response rate (ORR) of patients treated with above- mentioned regemen at 1, 3, 6 and 12 months after treatment was 79.7% (63/79), 69.6% (55/79), 63.3% (50/79) and 60.8% (48/79) respectivcly, out of which the ORR of glucocorticoid ineffective and glucocorticoid-dependent ITP patients treated with above-mentioned regimen at 1, 3, 6 and 12 months after treatment was 47.4% (9/19) vs 90.0% (54/60), 36.8% (7/19) vs 80.0% (48/60), 21.1% (4/19) vs 76.7% (46/60), 21.1% (4/19) vs 73.3% (44/60), and the difference between 2 groups was statistically significant. The detection of T reg cell showed that the T reg cell ratio in glucocorticoid- ineffective and dependent patients at 1, 3, 6 and 12 months after treatment was (1.70±0.43)% vs (3.47±0.72)%, (1.66±0.33)% vs (4.29±0.91)%, (1.71±0.37)% vs (4.44±0.97)%, (3.36±0.54)% vs (4.29±1.04)%, respectively. The detection of cytokines showed that the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-dependent patients at 1 month after treatment significanlly decreased (P＜0.05), the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-ineffective patients although decreased at 1 mouth after treatment, but there was no statistical difference as compared with glucocosticoid-depenment patients. CONCLUSION The treatment of glucocorticoid-dependent ITP patients with rituximab is more effective. The regulatory effect of rituximab on the T-reg cells, BAFF, IL-2 and sCD40L may be one of its mechanisms.
Dexamethasone ; Glucocorticoids ; Humans ; Inosine Triphosphate ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Rituximab ; therapeutic use

Disseminated Intravascular Coagulation ; Hematologic Diseases ; Humans ; Immunotherapy, Adoptive

Objective Serine /threonine kinases (STK) and phosphatases (STP) regulate various physiological activities of prokaryotes by reversible phosphorylation of proteins .This paper aimed to study the effects of simultaneous deletion of the stk and stp1 genes on the biological characteristics and pathogenicity of streptococcus suis type 2, the Chinese virulent strain 05ZYH33. Methods The double mutant of the stk and stp1 genes of 05ZYH33 was constructed by homologous recombination .The biological characteristics of the wild strain 05ZYH33 and the mutant strain Δstk/stp1 were compared.The effects of the stk and stp1 deletion on bacterial virulence was analyzed using cell adhesion assay , anti-phagocytosis assay and the mouse model of infection . Results RT-PCR showed that the stk and stp1 genes were replaced by the spectinomycin resistance gene Spc r and the mutant strain was successfully constructed .Experi-ments of biological characterization revealed gradually increased value of 05ZYH33 and Δstk/stp1 at 2 hours after inoculation and a plateau period at 7 hours.The logarithmic phase of the mutant strain (A600≈0.4) was 1 hour later than that of the wild one , and the bacterial den-sity of the former was lower than that of the latter after the plateau pe -riod (0.8 vs 1.0).On the blood plates of 05ZYH33 and Δstk/stp1 were observed greyish, round, semitransparent, wet and smooth-sur-faced tiny bacterial colonies , around which there were hemolysis rings with no significant differences in colony morphology and hemolytic ac -tivity.In the experiment on pathogenicity , the mice of the 05ZYH33 group all died within 12 hours while 9 of the 30 mice in the Δstk/stp1 group died within 12 hours and all died within 24 hours. Conclusion The simultaneous deletion of the stk and stp1 genes may mainly affect the regulation of the proteins associated with bacte -rial proliferation and division.

OBJECTIVETo explore the effect of Caspase 1 inhibitor Ac-YVAD-CMK on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT) and its mechanism.

METHODSExperiments were divided randomly into 3 groups: allogeneic hematopoietic stem cell transplantation combined with splenic cell infusion group (TS group, n=12), allogeneic hematopoietic stem cell transplantation combined with splenic cell infusion plus injection of low dose Caspase 1 inhibitor group (TS+low dose of C group, n=16) and plus high dose Caspase1 inhibitor (TS+high dose of C group, n=19). The body weight of mice in each group was dynamically detected, and the clinical manifestation of GVHD and score of aGVHD were determined, and the chimerism rate of mice was detected after transplantation for 14 days. Th1, Th2 and Th17 cells in peripheral blood were examined by flow cytometry. Peripheral proinflammatory cytokines IL-1β, IFN-γ, IL-1α and IL-18 were examined by enzyme-linked immunosorbent assay(ELISA). The tissues sections of GVHD target organs (liver, lung, colon and skin) were stained with HE for histopathologic examination and histopathologic score.

RESULTSAc-YVAD-CMK could alleviate murine aGVHD and pathological injury, decreare the incidence and severity of aGVHD in recipient mice. The detection of Th cell subsets in peripheral blood by flow cytometry showed that compared with TS group, the Th1 cell ratio in TS+low dose of C and TS+high dose of C groups was significantly reduced (P<0.05), while the Th2 and Th17 cell ratio was significantly enhanced (P<0.05) in TS+low dose of high dose of C groups. The detection of peripheral inflamematory cytokines by ELISA demonstrated that the inflammatory cytokines including IL-1β,IFN-γ,IL-18 and IL-1α were reduced significantly (P<0.05).

CONCLUSIONAc-YVAD-CMK can improve aGVHD by inhibiting Caspase 1 and reducing the release of some inflammatory cytokines, thereby alleviated the aGVHD pathological damage.