ObjectiveTo observe the therapeutic effects of Qishao Huoxue prescription on patients with lumbar disc herniation due to Qi stagnation and blood stasis and the effects of this prescription on hemorheological parameters and serum levels of inflammatory mediators. MethodA total of 86 patients with lumbar disc herniation due to Qi stagnation and blood stasis treated in the Wangjing Hospital of China Academy of Chinese Medical Sciences from January 2023 to February 2024 were selected and assigned according to the random number table into observation and control groups （n=43）. Patients in both groups received lumbar traction treatment. In addition， the observation group was orally treated with Qishao Huoxue prescription and the control group with celebrex for 3 weeks. The visual analogue scale （VAS） score， Oswestry disabilitiy index （ODI） score， 12-item Short-Form Survey （SF-12） score， traditional Chinese medicine （TCM） symptom score， hemorheological parameters ［whole blood high shear viscosity， middle shear viscosity， low shear viscosity， plasma viscosity （PV）， and fibrinogen （FIB）］， and the serum levels of inflammatory mediators ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and transforming growth factor-β₁ （TGF-β₁）］ were determined before and after treatment. In addition， the clinical efficacy and adverse reactions were observed and compared between the two groups. ResultAfter treatment， both groups showed declined VAS， ODI， and TCM symptom scores （P<0.05）， increased SF-12 physical component summary （PCS） and mental component summary （MCS） scores （P<0.05）. After treatment， the whole blood high shear viscosity， middle shear viscosity， low shear viscosity， PV， and FIB decreased in the observation group （P<0.05）， while they did not show significant variations in the control group. After treatment， both groups of patients showed reductions in TNF-α， IL-6， and IL-1β levels and an elevation in the TGF-β₁ level （P<0.05）. Compared with the control group after treatment， the observation group showed decreases in VAS， ODI， TCM symptom scores and main symptom scores （P<0.05）， no significant differences in the secondary symptom scores， increased PCS and MCS scores （P<0.05）. The observation group outperformed the control group in terms of recovering whole blood high shear viscosity， middle shear viscosity， low shear viscosity， PV， FIB， TNF-α， IL-6， IL-1β， and TGF-β₁ （P<0.05）. The total response rate in the observation group was 97.5% （40/41）， which was higher than that （88.1%， 37/42） in the control group （P<0.05）. No serious adverse reaction was observed in the two groups during the observation period. One case in the observation group showed subcutaneous bruising on the lower limbs， which gradually disappeared after withdrawal. ConclusionQishao Huoxue prescription demonstrated definite effect in treating lumbar disc herniation due to qi stagnation and blood stasis by recovering hemorheological parameters and inhibiting the expression of inflammatory mediators in the serum without inducing adverse reactions. It is worth applying in clinical practice.

Background Clozapine belongs to atypical antipsychotic drugs that has shown significant efficacy in treating schizophrenia.However,clozapine can induce arrhythmias in patients.Currently,there is a lack of systematic research on the types and incidence of clozapine-induced arrhythmias.Objective To explore the types and incidence of arrhythmias in patients with schizophrenia induced by clozapine through Meta-analysis,so as to provide references for clinical treatment.Methods On October 31,2022,a search was conducted through PubMed,Embase,Cochrane Library and China National Knowledge Infrastructure(CNKI)to collect relevant literature on clozapine-induced arrhythmia in patients with schizophrenia.Joanna Briggs Institute(JBI)was used to evaluate the quality of the included literature.Meta-analysis was conducted using Review Manager 5.4.Results A total of 12 studies were included,involving 42 490 schizophrenia patients taking clozapine.The incidence of arrhythmias caused by clozapine was 23％(95％CI:0.16～0.29).Among them,the incidence of tachycardia was 25％(95％CI:0.15～0.35),atrial arrhythmia was 6％(95％CI:-0.02～0.14),ventricular arrhythmia was 7％(95％CI:-0.02～0.16),conduction block was 2％(95％CI:0～0.04),QTc prolongation was 4％(95％CI:-0.04～0.12)and T-wave changes was 23％(95％CI:0.16～0.30).Conclusion Schizophrenia patients taking clozapine may increase their risk of developing arrhythmia,with tachycardia being the most prevalent.

Background::Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients.Methods::We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177 + neutrophils, and CD40L + T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs. persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. Results::We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X 1 + 0.758X 2 + 1.347X 3 - 7.745 (X 1, X 2, and X 3 represent the proportions of CD177 + neutrophils, eosinophils, and CD40L + T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% ( P <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing ( P <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. Conclusions::ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC.Registration::Chinese Clinical Trial Registry, No. ChiCTR2300077792.

As a branched chain amino acid, L-valine is widely used in the medicine and feed sectors. In this study, a microbial cell factory for efficient production of L-valine was constructed by combining various metabolic engineering strategies. First, precursor supply for L-valine biosynthesis was enhanced by strengthening the glycolysis pathway and weakening the metabolic pathway of by-products. Subsequently, the key enzyme in the L-valine synthesis pathway, acetylhydroxylate synthase, was engineered by site-directed mutation to relieve the feedback inhibition of the engineered strain. Moreover, promoter engineering was used to optimize the gene expression level of key enzymes in L-valine biosynthetic pathway. Furthermore, cofactor engineering was adopted to change the cofactor preference of acetohydroxyacid isomeroreductase and branched-chain amino acid aminotransferase from NADPH to NADH. The engineered strain C. glutamicum K020 showed a significant increase in L-valine titer, yield and productivity in 5 L fed-batch bioreactor, up to 110 g/L, 0.51 g/g and 2.29 g/(L‧h), respectively.
Valine ; Corynebacterium glutamicum/genetics* ; Metabolic Engineering ; Amino Acids, Branched-Chain ; Bioreactors

Objective:To investigate the differences of spontaneous neural activity and functional connectivity between bilateral symmetrical voxels in the local brain regions at resting-state of methamphetamine (MA) dependent patients and healthy controls (HCs).Methods:Forty-six MA-dependent patients, admitted to and received drug rehabilitation treatment for the first time in our hospital from February 2014 to October 2019, and 46 HCs matched with age, gender and education level during the same period were enrolled in this study. The resting state functional magnetic resonance imaging (rs-fMRI) data of these subjects were collected; the static and dynamic regional homogeneity (ReHo, d-ReHo) and static and dynamic voxel-mirrored homotopic connectivity (VMHC, d-VMHC) were used to evaluate MA-related alterations of brain spontaneous activity and interhemispheric functional connectivity. The correlations of brief psychiatric rating scale (BPRS) scores with above values in the brain regions with significant inter-group differences were analyzed.Results:As compared with the HCs, the MA-dependent patients had significantly decreased ReHo in the left medial orbitofrontal cortex (mOFC), and significantly increased d-ReHo in the left mOFC, left middle frontal gyrus, bilateral inferior frontal gyrus, left precentral gyrus and left postcentral gyrus ( P<0.05). As compared with the HCs, the MA-dependent patients had significantly decreased VMHC in the bilateral mOFC, precentral gyrus and postcentral gyrus ( P<0.05). The ReHo, VMHC, d-ReHo, and d-VMHC were not significantly correlated with total scores and each factor scores of BPRS, and total dose of MA (after removing outliers) in MA-dependent patients ( P>0.05). Conclusion:During resting state, MA-dependent patients show obvious abnormalities in the coordination and stability of spontaneous neural activity and the coordination of interhemispheric activity in local brain regions, especially in the mOFC; abnormal ReHo, d-ReHo and VMHC in left mOFC may be important neuroimaging biomarkers for MA-dependence.

Objective: To investigate the effect of apigenin on the proliferation, migration, invasion, apoptosis and autophagy of human lung squamous carcinoma NCI-H520 cells. Methods: Human lung squamous carcinoma NCI-H520 cells were culturedin vitro, and the CCK-8 method was used to detect the effects of different concentrations of apigenin(2.5, 5, 10, 20 μmol/L) or cisplatin(2.5, 5, 10, 20 μmol/L) on cell viability. Carboxyfluorescein diacetate, succinimidyl ester(CFDA SE) was used to detect the effect of apigenin or cisplatin on cell division. Scratch test and Transwell test were used to detect the effect of apigenin on cell migration and invasion. Annexin V/PI double staining method and Hoechst 33258 nuclear staining method were used to detect the effect of apigenin on cell apoptosis. Transmission electron microscopy was used to observe the generation of autophagic vesicles in cells. Acridine orange(AO) staining was used to observe the changes of acidic organelles in cells. Western blot was used to detect microtubule-associated protein 1 light chain 3 B-Ⅱ(LC3 B-Ⅱ) and p62 protein expression. Results: Compared with the control group, CCK-8 assay and CFDA SE showed that apigenin or cisplatin reduced proliferation of NCI-H520 cells(P<0.05). Scratch test and Transwell test showed that apigenin reduced the migration and invasion levels of cells(P<0.01). Annexin V/PI double staining showed that apigenin increased apoptosis rate(P<0.05). Hoechst 33258 nuclear staining showed that apigenin promoted nuclear condensation and hyperchromatism of cells. AO staining fluorescence value enhanced, the autophagy bimolecular structure appeared under transmission electron microscopy, and the results of LC3 B-Ⅱ and p62 protein expression levels in Western blot showed that apigenin increased the autophagy level of cell NCI-H520(P<0.05). Chloroquine(CQ) failed to increase the protein levels of LC3 B-Ⅱ and p62 in apigenin treated cells. Conclusion Apigenin at different concentrations can inhibit the proliferation, migration and invasion of human lung squamous cell carcinoma NCI-H520, and its inhibition of cell growth and metastasis may be related to the induction of apoptosis and autophagy, and the increase of autophagy may be caused by blocking autophagosome degradation.

Objective:To investigate the topological alterations of brain functional networks in patients with chronic methamphetamine (MA) dependence.Methods:Resting-state functional magnetic resonance imaging was used to map the brain networks of 46 patients with MA-dependence (MA group) and 46 healthy controls (control group). Statistical methods were used to compare the differences of brain functional connection and topological parameters between the two groups, and the correlations between these topological parameters with significant inter-group differences and clinical measurements were analyzed.Results:(1) Brain functional connection: as compared with the control group, the MA group had significantly enhanced functional connectivity in the subnetworks consisting of several brain regions, including the inferior parietal lobule, posterior central gyrus, lateral occipital cortex, ventromedial occipital cortex, orbital gyrus, anterior central gyrus, fusiform gyrus, superior temporal gyrus and thalamus; as compared with the control group, the MA group had significantly attenuated functional connectivity in the subnetworks consisting of several brain regions, the orbit frontal cortex, precentral gyrus, paracenter lobule, inferior temporal gyrus, fusiform gyrus, parahippocampal gyrus, superior parietal lobule, postcentral gyrus, medioventral occipital cortex, lateral occipital cortex and amygdala. (2) Network topology attributes: the brain functional networks in all subjects from the MA group and control group held worldlet; but attribute of worldlet in the MA group was significantly reduced as compared with that in the control group ( P<0.05); moreover, the MA group had significantly decreased clustering coefficient, local efficiency, and modularity as compared with the control group ( P<0.05). In terms of regional topological attributes, such as betweenness centrality, the MA group presented evident reduction in the left superior frontal gyrus, right orbit frontal cortex, right middle temporal gyrus and right/left lateral occipital cortex as compared with the control group with significant differences ( P<0.05). (3)Correlation analysis: the betweenness centrality of right middle temporal gyrus exhibited a positive correlation with the age of patients using MA for the first time ( r=0.327, P=0.028); a positive correlation was found between the modularity and activating factor scores in Brief Psychiatric Rating Scale (BPRS) in MA group ( r=0.315, P=0.035). Conclusions:Part of the global/local topological attributes of the brain functional network of patients with MA addiction are damaged. The younger the patients are when they take MA for the first time, the lower the betweenness centrality of the right middle temporal gyrus; the more the local attributes are damaged; and furthermore, the deeper the network modularity, the severer the active symptoms in the psychotic symptoms.

Objective:To analyze the compliance and related factors of low-dose computed tomography (LDCT) screening among the high-risk population of lung cancer in three provinces participating in the cancer early diagnosis and early treatment program in urban areas of China.Methods:From October 2017 to October 2018, 17 983 people aged between 40 and 74 years old at high risk of lung cancer were recruited from Zhejiang, Anhui and Liaoning provinces. The basic demographic characteristics, living habits, history of the disease and family history of cancer were collected by using a cancer risk assessment questionnaire, and the data of participants examined by LDCT were obtained from the hospitals participating in the program. The screening compliance was quantified by the screening participation rate, and it was calculated as the proportion of participants completing LDCT scan among high-risk population. The related factors of LDCT screening compliance were analyzed by using a multivariate logistic regression model.Results:The age of 17 983 participants was (56.52±8.22) years old. Males accounted for 51.9% (N=9 332), and 69.5% (N=12 495) had ever smoked, including former smokers and current smokers. A total of 6 269 participants were screened by LDCT, and the screening participation rate was 34.86%. The results of multivariate logistic regression analysis showed that the age group of 50 to 69 years old, female, passive smokers, alcohol consumption, family history of lung cancer and history of chronic respiratory diseases were more likely to be screened by LDCT, while the compliance of LDCT screening in current smokers was low.Conclusions:The LDCT screening compliance of the high-risk population of lung cancer in urban areas of China still needs to be improved. Age, sex, smoking, drinking, family history of lung cancer and history of chronic respiratory disease are associated with screening compliance.

Objective:To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients.Methods:The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed.Results:The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively ( P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively ( P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm 3, the median survival time of SIB and No-SIB group was 34.7 and 30.3 months ( P=0.155), respectively. In the patients whose GTV volume>50 cm 3, the median survival time of SIB and No-SIB group was 16.1 and 20.1 months ( P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group ( P<0.001). Conclusions:The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

Objective:To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients.Methods:The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed.Results:The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively ( P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively ( P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm 3, the median survival time of SIB and No-SIB group was 34.7 and 30.3 months ( P=0.155), respectively. In the patients whose GTV volume>50 cm 3, the median survival time of SIB and No-SIB group was 16.1 and 20.1 months ( P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group ( P<0.001). Conclusions:The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.