Objective To investigate the effects of leonurine on tumor growth and immune function of colon cancer tumor bearing mice.Methods C57BL/6 mice were established a colon cancer bearing mouse model.After modeling,the mice were randomly divided into control group(0.9％NaCl),experimental-L group(180 ng·g-1 leonurine),experimental-H group(360 ng·g-1 Leonurine),experimental-H+NC group(360 ng·g-1 leonurine+no-load plasmid),and experimental-H+sicGAS group(360 ng·g-1 leonurine+cGAS siRNA plasmid).Tumor volume and weight were measured after group treatment.Immunohistochemical staining was used to detect the relative positive expression of cyclic GMP-AMP synthase(cGAS),stimulator of interferon gene(STING)and the average positive number of CD4+T and CD8+T cells in tumor tissues.The killing rate of mouse CD4+T and CD8+T cells to tumor cells was detected by cell counting kit 8.Results The tumor volume of control group,experimental-H group,experimental-H+NC group and experimental-H+cGAS knockout group were(1 088.32±70.82),(468.20±24.28),(480.01±23.78)and(998.99±32.84)mm3,respectively;the relative positive expressions of cGAS were 1.00±0.00,5.18±0.73,5.30±0.80 and 1.12±0.46,respectively;the relative positive expressions of STING were 1.00±0.00,5.64±0.81,5.48±0.75 and 1.14±0.50,respectively;the mean CD4+T positive cells were 40.25±5.82,118.64±15.30,113.25±16.65 and 48.74±7.10,respectively;the average number of CD8+T positive cells were 49.76±6.12,143.68±16.80,135.75±17.42 and 57.01±8.24,respectively.The above indexes in experimental-H group and experimental-H+no-load group were statistically significant compared with control group(all P＜0.05);there were statistically significant differences in the above indexes between the experimental-H+sicGAS group and the experimental-H group(all P＜0.05).Conclusion Leonurine can enhance the proliferation ability of lymphocytes in colon cancer tumor bearing mice by activating cGAS-STING signal,and inhibit tumor growth in mice.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective:To explore the potential causal relationship between gut microbiota and teratozoospermia.Methods:We searched the database of Genome-Wide Association Study(GWAS)for gut microbiota-and teratozoospermia-related data.We used gut microbiota as an exposure factor,determined the instrumental variables according to the GWAS data on 18 340 participants released by the MiBioGen Alliance,and derived the outcome variables from the European data on teratozoospermia,with a sample size of 85 716,including 915 cases and 209 006 controls.Using inverse-variance weighting(IVW),MR-Egger regression and the weighted median estimator(WME),we performed two-sample Mendelian randomization(MR)analysis on the retrieved data,and estimated the causal relationship between gut microbiota and teratozoospermia based on the β value.Results:Two-sample MR analysis indicated that the class Erysipelotrichia,family Erysipelotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridialesm and order Erysipelotrichales were causally related with the increased risk,while the family Porphyromonadaceae with the decreased risk of teratozoospermia.Conclusion:The class Erysipelotrichia,family Erysipe-lotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridia-lesm and order Erysipelotrichales are one of the causes of teratozoospermia,related to the increased risk of the condition,while the family Porphyromonadaceae has a protective effect on sperm morphology,reducing the risk of teratozoospermia.

Objective To simulate the microflow field environment between the anastomotic nail surface and intestinal wall tissue after implantation and to study the effect of hydrophobic surfaces on the flow rate of extracellular fluid and the fluid shear force on the wall to regulate bacterial adhesion through changes in the flow field.Methods The microstructure of shark skin was observed,and a simplified two-dimensional(2D)movement model of bacteria in a microflow field was established.Using computational fluid dynamics(CFD)numerical simulation,the movement of bacteria on a smooth surface and micro-textured surface in a static and dynamic flow field were simulated.The flow field characteristics around bacteria and the magnitude of fluid shear force under the two surface environments were compared,and the internal mechanism of the fluid shear force affecting bacterial adhesion was analyzed.Results The addition of the biomimetic microtexture enhanced the flow rate of the extracellular fluid in the microflow field,and the fluid had little viscous effect on the bacteria in the static flow field.The fluid in the dynamic flow field had a stronger pushing effect on the bacteria.The fluid shear force on the microtextured wall increased when the pit width was within a specific range.Conclusions The bionic micro-textured surface of the anastomotic nail can accelerate the flow rate of extracellular fluid,increase the fluid shear force of micro-textured walls and bacteria,and influence bacterial adhesion.These result provide a theoretical basis for studying bacteriostatic surfaces of anastomotic nails.

Objective To investigate the clinical efficacy of Xuanfei Yipi Formula,a prescription derived from modified Jianpi Pill recorded in Yi Fang Ji Jie(A Collection of Prescriptions with Expositions),in treating senile sarcopenia with spleen-stomach weakness type,and to observe its effect on chronic low-grade inflammation of the patients.Methods Seventy cases of senile sarcopenia patients of spleen-stomach weakness type were randomly divided into an observation group and a control group,with 35 cases in each group.The control group was given exercise and nutritional guidance,while the observation group was treated with Xuanfei Yipi Formula orally on the basis of the control group,and the intervention time of both groups was eight weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,appendicular skeletal muscle mass index(ASMI),grip strength,6-meter walking pace,and the serum levels of C-reactive protein(CRP),interleukin 6(IL-6),tumor necrosis factor α(TNF-α)in the two groups before and after treatment were observed.After treatment,the clinical efficacy and safety of the patients in the two groups were evaluated.Results(1)After eight weeks of treatment,the total effective rate in the observation group was 94.29%(33/35),and that in the control group was 77.14%(27/35),the intergroup comparison(by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of TCM syndrome score in the observation group was more obviously than that in the control group(P＜0.01).(3)After eight weeks of treatment,the ASMI,grip strength and 6-meter walking pace in the two groups were significantly higher than those before treatment,and the increase of ASMI and grip strength in the observation group was more obviously than that in the control group(P＜0.05).(4)After eight weeks of treatment,the levels of serum CRP,IL-6,and TNF-α in the two groups were decreased significantly compared with those before treatment(P＜0.05),and the decrease of serum CRP level in the observation group was more obviously than that in the control group(P＜0.05).(5)During the treatment,no obvious adverse reactions occurred in both groups,and the safety indexes of liver and kidney functions of the patients were all within the normal range.Conclusion Xuanfei Yipi Formula can improve the clinical symptoms of senile sarcopenia patients,and its mechanism is probably related with the regulation of chronic low-grade inflammation.

Objective To investigate whether the combination of conventional respiratory training and articulatory visual feedback training can improve respiratory function and diaphragmatic function in stroke patients.Methods This single-blind randomized controlled trial recruited a total of 30 stroke patients who were admitted to Department of Rehabilitation Medicine,Zhongshan Hospital,Fudan University,from Nov 2022 to Aug 2023,and divided them into two groups:a experimental group(n=15)and a control group(n=15).The experimental group received conventional respiratory training combined with articulatory visual feedback training,and the control group received conventional respiratory training.The training in the 2 groups was conducted 5 times per week for 4 weeks.Results Both groups significantly improved in maximum inspiratory pressure(MIP),peak inspiratory flow(PIF),maximum phonation time(MPT),maximum counting ability(MCA),and peak expiratory flow(PEF)in each of the two groups improved significantly after training(P<0.05).After training,compared with the control group,the experimental group showed significant differences in MIP[(46.04±13.58)cmH2O vs.(63.46±16.96)cmH2O;P=0.004;95%CI:-28.91,-5.93;effect size(ES)=1.13],PIF[(144.00±43.81)L/min vs.(190.20±75.01)L/min;P=0.049;95%CI:-1.54,0;ES=0.75],MCA[(7.06±3.25)s vs.(10.30±4.89)s;P=0.041;95%CI:-6.34,-0.13;ES=0.77],forced vital capacity(FVC)[(1.74±0.76)L vs.(2.26±0.57)L;P=0.04;95%CI:-1.03,-0.03;ES=0.77],forced expiratory volume in one second(FEV1)[(1.10±0.40)L vs.(1.60±0.50)L;P=0.004;95%CI:-0.85,-0.18;ES=1.1],and PEF[(83.40(55.80)L/min vs.171.12(94.80)L/min;P=0.012)].However,there were no statistically significant differences after training between the two groups in the maximum phonation time(MPT),vital capacity(VC),maximum voluntary ventilation(MVV),diaphragm mobility of the nonparetic side and paretic side,thickening fraction of the nonparetic side and paretic side.Conclusion Compared with conventional respiratory training alone,the combination of articulatory visual feedback training with conventional respiratory training is more effective in enhancing respiratory and lung function in stroke.

The CRISPR/Cas is an immune defense system acquired by prokaryotes to resist the invasion of foreign genetic materials during their evolutionary process.In recent years,it has been developed into an efficient tool for genome editing,gene regulation and molecular diagnosis.Its programmable targeting mechanism has opened the door to use this system for genome manipulation and allows for dynamic regu-lation and control of gene expression within its activity range.As one of the most flexible and cost-effec-tive techniques among existing gene modification methods,it has been widely applied in clinical disease treatment,industrial and agricultural production,sustainable dye development,chemical processing and many other fields.With the continuous investigation and exploration of the CRISPR/Cas system,a large number of studies have been reported on the engineering modification and optimization approaches of gRNA,including changing the length of the spacer region,regulating the structure of constant and varia-ble sequence parts,adding extra functional sequences through the end or middle extension,and chemical synthesis modifications,in order to reduce off-target and mutation rates,improve the efficiency of the CRISPR system,and fully stimulate the potential of CRISPR gene manipulation tools in biomedical fields.Based on this,this review will introduce the latest progress in gRNA engineering design strategies and application research of CRISPR/Cas9 and CRISPR/Cas12 systems,analyze and discuss the opportu-nities and challenges in the current gRNA engineering technology,aiming to provide ideas and reference directions for obtaining gRNAs with better performance,thereby effectively improving the ability to probe the human genomes using the CRISPR/Cas system and bringing more possibilities to programmable biology.

Objective:To explore the efficacy and safety of haploidentical hematopoietic stem cell transplantation combined with umbilical cord blood infusion for the treatment of aplastic anaemia in children.Methods:Nine cases of children with aplastic anaemia treated with umbilical cord blood combined with haploidentical hematopoietic stem cell transplantation at the People's Hospital of Henan University of Chinese Medicine from January 1,2021 to September 15,2023 with a median age of 11(2-13)years and a median follow up of 18(7.5-21)months were included,and the clinical data were retrospectively analyzed.Hematopoiesis reconstitution,the incidence of graft-versus-host disease(GVHD),infections and survival of the patients were analyzed.Results:All 9 children were successfully implanted.The median time to neutrophil and platelet implantation was 11.11±1.27 d and 12.44±3.36 d,respectively.One case developed acute gastrointestinal GVHD of degree I,which was improved after treatment,and the patient developed superficial gastritis and chronic gastrointestinal GVHD at a later stage,which is currently under clinical follow-up.Acute GVHD of Ⅱ-Ⅳ degree was 0％.Hemorrhagic cystitis in 3 cases,CMV infection in 5 cases and bacterial and fungal infections in 5 cases improved with symptomatic treatment.All 9 children demonstrated complete donor chimerism within 1 month after transplantation,at two years of follow-up,all nine children survived without recurrence or development of grade Ⅱ-Ⅳ GVHD,and there were no children with transplant-related deaths.Conclusion:Haploidentical hematopoietic stem cell transplantation combined with umbilical cord blood transfusion for aplastic anaemia in children has a low incidence and mild degree of GVHD,with significant efficacy,and can be used as a therapeutic option for children without an HLA full donor chimeric match.

Purpose: To report on the local control and toxicity of 5-fraction, high-conformal ultrafractionated radiation therapy (RT) for primary tumors in patients with metastatic breast cancer (MBC) who did not undergo planned surgical intervention. Methods: We retrospectively reviewed 27 patients with MBC who underwent 5-fraction high-dose ultrafractionated intensity-modulated RT for their primary tumors between 2017 and 2022 at our institution. A median dose of 66.8 Gy (range, 51.8–83.6 Gy) was prescribed to the gross tumor, calculated in 2-Gy equivalents using an α/β ratio of 3.5, along with a simultaneous integrated boost of 81.5%. The primary endpoint of this study was local control. Results: The median tumor size and volume were 5.1 cm and 112.4 cm3 , respectively. Treatment was generally well tolerated, with only 15% of the patients experiencing mild acute skin toxicity, which resolved spontaneously. The best infield response rate was 82%, with the objective response observed at a median time of 10.8 months post-RT (range, 1.4–29.2), until local progression or the last follow-up. At a median follow-up of 18.3 months, the 2-year local control rate was 77%. A higher number of prior lines of systemic therapy was significantly associated with poorer 2-year local control (one–two lines, 94% vs three or more lines, 34%; p = 0.004). Post-RT, 67% of the patients transitioned to the next line of systemic therapy, and the median duration of maintaining the same systemic therapy post-RT was 16.3 months (range, 1.9–40.3). Conclusion In our small dataset, 5-fraction, high-conformal ultrahypofractionated breast RT offered promising 2-year local control with minimal toxicity. Further studies are warranted to investigate the optimal dose and role in this setting.

Humans ; Child ; Neurofibromatosis 1/drug therapy* ; Benzimidazoles/therapeutic use*