ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Objective To evaluate the efficacy and safety of tacrolimus extended-release (Tac-ER) in the early stage after kidney transplantation. Methods Clinical data of 68 recipients undergoing kidney transplantation from 34 pairs of renal allografts were retrospectively analyzed. Two recipients who received bilateral kidneys from the same donor were treated with Tac-ER (Tac-ER group) and tacrolimus immediate-release (Tac-IR) (Tac-IR group) as one of the basic immunosuppressant. The changes of tacrolimus dosage and blood concentration, intra-patient variability (IPV), renal function, incidence of acute rejection, recipient and allograft survival rates and adverse events were statistically compared between two groups. Results The average daily dose of tacrolimus in the Tac-ER group was significantly higher than that in the Tac-IR group (F=8.386, P=0.005). In the Tac-ER group, the mean trough concentration at postoperative 4 d was (6.14±4.04) ng/mL, did not reach the target concentration, significantly lower than (9.41±5.47) ng/mL in the Tac-IR group (F=7.854, P=0.007). In the Tac-ER group, the IPV of trough concentration of tacrolimus within postoperative 1 month was significantly higher than that in the Tac-IR group (0.44±0.15 vs. 0.36±0.12, P=0.032). At postoperative 6 months, there was no significant difference in the renal function between two groups [serum creatinine level was (126±26) μmol/L vs. (120±28) μmol/L, and the estimated glomerular filtration rate was (56±13) mL/(min·1.73 m²) vs. (60±15) mL/(min·1.73 m²), both P > 0.05]. The allograft and recipient survival rates were 100% in both groups. The incidence of acute rejection within postoperative 1 month was 18% in the Tac-ER group and 3% in the Tac-IR group, with no significant difference (P > 0.05). The overall incidence of adverse events was 94% in the Tac-ER group and 97% in the Tac-IR group, with no significant difference (P > 0.05). Conclusions The efficacy and safety of Tac-ER are equivalent to those of Tac-IR, whereas a higher dose of Tac-ER should be orally given to reach the blood concentration similar to that of Tac-IR. During early-stage drug treatment, Tac-ER should be orally given before kidney transplantation or inittally with loading dose, aiming to increase the systemic exposure to tacrolimus early after kidney transplantation and prevent acute rejection caused by insufficient exposure.

OBJECTIVE: To provide prenatal diagnosis, pedigree analysis and genetic counseling for a pregnant woman who had given birth to a child featuring global developmental delay. METHODS: A pregnant woman who underwent prenatal diagnosis at the Affiliated Hospital of Southwest Medical University in August 2021 was selected as the study subject. Peripheral blood samples were collected from the woman, her husband and child, in addition with amniotic fluid sample during mid-pregnancy. Genetic variants were detected by G-banded karyotyping analysis and copy number variation sequencing (CNV-seq). Pathogenicity of the variant was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was traced in the pedigree to assess the recurrence risk. RESULTS: The karyotypes of the pregnant woman, her fetus, and affected child were 46,XX,ins(18)(p11.2q21q22), 46,X?,rec(18)dup(18)(q21q22)ins(18)(p11.2q21q22)mat and 46,XY,rec(18)del(18)(q21q22)ins(18)(p11.2q21q22)mat, respectively. Her husband was found to have a normal karyotype. CNV-seq has revealed a 19.73 Mb duplication at 18q21.2-q22.3 in the fetus and a 19.77 Mb deletion at 18q21.2-q22.3 in her child. The duplication and deletion fragments were identical to the insertional fragment in the pregnant woman. Based on the ACMG guidelines, the duplication and deletion fragments were both predicted to be pathogenic. CONCLUSION The intrachromosomal insertion of 18q21.2-q22.3 carried by the pregnant woman had probably given rise to the 18q21.2-q22.3 duplication and deletion in the two offspring. Above finding has provided a basis for genetic counseling for this pedigree.
Child ; Female ; Humans ; Pregnancy ; DNA Copy Number Variations ; East Asian People ; Pedigree ; Prenatal Diagnosis/methods* ; Chromosomes, Human, Pair 18/genetics* ; Male ; Fetus ; INDEL Mutation

Objective:To observe the safety and efficacy of early conversion into a simplified once-daily immunosuppressive regimen of sirolimus plus low-dose extended-release tacrolimus in kidney transplant recipients.Methods:From April 2019 to August 2020, clinical data were collected from 44 recipients (22 pairs) of kidney transplantation. Two kidneys from the same donor were randomly divided into observed and control groups. The immunosuppressive regimen of two groups was the same within 1 month post-transplantation, i. e. tacrolimus plus mycophenolatemofetil (or mycophenolate sodium) and prednisone. Then the immunosuppressive regimen of observed group was switched into a simplified once-daily regimen of sirolimus plus low-dose extended-release tacrolimus and prednisone while control group remained unchanged. The changes of graft function, proteinuria and the incidence of related adverse events were recorded.Results:No inter-group difference existed in serum level of creatinine at Month 1 post-transplantation (163.40±51.57 vs 166.10±49.48 μmol/L). After regimen conversion, serum level of creatinine was slightly lower in observed group than that in control group at Months 3 and 6 post-transplantation (130.10±30.10 vs 134.90±28.97, 121.50±24.96 vs 136.30±27.06). However, there was no statistic difference. The 24-hour urinary total trace protein was slightly higher in observed group than that in control group (331.20±84.21 vs 279.50±80.91 and 209.60±66.02 vs 179.50±37.60 mg/24 h) at Months 3 and 6 post-transplantation. However, there was no statistic difference. No inter-group difference existed in the incidence of drug side effects or other adverse events.Conclusions:In kidney transplant recipients at Month 1 post-transplantation, a conversion of immunosuppressive regimen into a simplified once-daily of sirolimus plus low-dose extended-release tacrolimus can significantly boost patient compliance without an elevated risk of drug side effects or adverse events and offer an advantage of reducing nephrotoxicity.

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191

Objective To establish a Chinese expert consensus of the surgical management for type A aortic dissection (TAAD) by using the Delphi method.Methods A systematic review of the previously published literature related to management of TAAD at home and abroad was conducted to formulate a questionnaire of clinical consensus of the surgical treatment for TAAD.This questionnaire including seven aspects of surgical management for TAAD,namely contraindications to operative management,cannulation site,target temperature during circulation arrest,cerebral perfusion strategy,surgical procedure,distal anastomotic technique and surgical management for patients with connective tissue disease such as Marfan syndrome.From October 2015 to April 2016,we performed two rounds Delphi survey in which the current professional opinions from 55 experienced and representative cardiovascular surgeons in China,were gathered and analysed.Results The responses rates of two rounds were 80.0％ (44/55) and 77.27％ (34/44).The scores of authoritative coefficient was 0.87 and 0.83.The coefficient of concordance were 0.31 (P ＜ 0.05) and 0.32 (P ＜ 0.05).After two rounds of consultation,consensus of the surgical management for TAAD was reached on 16 items of seven aspects.Conclusion This Delphi study established an initial Chinese expert consensus concerning the surgical management for TAAD,which drew credible results and reliable conclusions.This study will helo to standardize the surgical management of TAAD in China.

Objective To investigate the curative effect of mammotome minimally invasive operation in the treatment of benign breast disease and analyse its characteristics.Methods Two hundred and five cases of benign breast disease patients admitted to the hospital in time sequence were divided into the observation group (105 cases) and control group(100 cases).Observation group used mammotome minimally invasive rotary cutting operation,and the control group used conventional breast tumor resection.The surgical results of two groups of patients,tumor complete resection or not,whether the patients for surgery satisfaction were observed.Patients of two groups were compared with intraoperative and postoperative relevant indicators,and the postoperative complications.Results In the observation group,105 patients with mammotome spiral cutting knife surgery of breast masses were completely resected,the satisfaction of patients for surgery was 96.2％ (101/ 105),significantly higher than that of control group(81.0％ (81/100),x2 =4.187,P＜0.05).The operative time,blood loss,length of incision values of observation group were significantly lower than those in the control group((17.30±6.70) min vs (57.23 ± 8.96) min,(10.43 ± 5.14) ml vs (109.16 ± 13.45) ml,(10.27 ±0.06) cm vs (1.43±0.12) cm;t=18.741,26.167,11.421;P＜0.05),the postoperative recovery time and the scar length were significantly lower than the control group((4.1±2.5) d vs (8.0±3.5) d,(0.15±0.03) cm vs (1.21±0.46) cm;t =5.176,2.647;P＜0.05),breast deformation cases,tumor residual proporation were 1.9％(2/105) and 0(0/105),fewer than that in the control group(12.0％(12/100),9.0％(9/100);x2=6.721,11.470;P＜0.05).In control group breast deformation subcutaneous hematoma and ecchymosis,wound infection,skin damage,pain,pigment calm incidence were 2.9％ (3/105),5.7％ (6/105),1.9％ (2/105),2.9％(3/105),8.6％(9/105),2.9％(3/105),significantly lower than those in the observation group(9.0％(9/100),12.0(12/100),7.0％ (7/100),16.0％(16/100),23.0％(23/100),8.0％(8/100);x2 =2.164,3.071,2.467,6.194,6.177,2.642;P＜ 0.05).Conclusion Mammotome minimally invasive rotary cut scalpel compare with conventional breast tumor excision undoubtedly has a more significant curative effect and patient satisfaction and have the characteristics of operation safety,efficiency,beautiful,fewer complications,humanized.

Aim To synthesize 8-bromo-ethoxy Rhein and investigate its mechanisms and inhibition effect on hepatitis B surface antigen ( HBsAg ) and e antigen ( HBeAg) in HepG2.2.15 cells.Methods 8-bromo-ethoxy Rhein was synthesized based on the chemical structure of Rhein , and its structure was identified by IR,1 H-NMR and 13 C-NMR spectra.MTT assay was used to test the inhibitory effect of 8-bromo-ethoxy Rhein on HepG2.2.15 cells.After the cells treatment by 8-bromo-ethoxy Rhein , the HBsAg and HBeAg in cell supernatant were detected by ELISA .The expres-sion of hepatitis B virus X gene ( HBx) was detected by Western blot .The cell cycles were examined with flow cytometry.The intracellular free calcium concentration was detected by laser scanning confocal microscopy . Results The structure of 8-bromo-ethoxy Rhein was confirmed by IR,1 H-NMR and 13 C-NMR.MTT results showed that synthetic product and Rhein could inhibit the cell proliferation in HepG2.2.15 cells.After trea-ted with 8-bromo-ethoxy Rhein and Rhein for 72 h,the half inhibitory concentration 50%( IC50 ) was 14.29 mg? L-1 and 11.59 mg? L-1 , respectively .Using non-cytotoxic dose of 8-bromo-ethoxy Rhein , the inhibitory effect on HBsAg and HBeAg was gradually enhanced with increasing 8-bromo-ethoxy Rhein concentration . The inhibitory effect of synthetic product on hepatitis B virus was better than that of Rhein .8-bromo-ethoxy Rhein could down-regulate the expression of HBx , in-tracellular calcium ion concentration and block the hepatitis B virus ( HBV ) replication.Flow cytometry results showed 8-bromo-ethoxy Rhein didn′t affect the cell cycle .Conclusions Compare with Rhein , the synthesis of 8-bromo-ethoxy Rhein shows stronger inhi-bition on hepatitis B virus in HepG2.2.15, and its mechanisms may involve down-regulating the expres-sion of HBx and reducing calcium ion concentration .

Objective To investigate the effect of insulin-like growth factor 1 antibody (IGF-1Ab) on motor endplate function after injection ofbotulinum toxin A (Btx-A).Methods The total 90 male SD rats were randomly divided into 4 groups:control group,Btx-A group and 2 ug and 20 ug IGF-1Ab groups.In Btx-A and IGF-1Ab groups,a volume of 0.5 U (0.1 mL) Btx-A was intramuscularly injected into a site in the fight gastrocnemius muscle;on day 3,equal volumes (0.1 mL) of IGF-1Ab with a dosage of 2 ug and 20 ug were injected to the 2 ug and 20 ug IGF-1Ab groups respectively at the same site.The gastrocnemius muscle strength and the mean optical density (MOI) value of the positive reaction zone of acetylcholine esterase staining were evaluated at different time points.Results The gastrocnemius muscle strength increased from 12.34±0.16 g before injection to 7.70±0.90 g after injection in the Btx-A group;the gastrocnemius muscle strength decreased in other groups after injection of Btx-A;on day 14,28,42,56 and 70,the muscle strength oflGF-1Ab groups was significantly lower than that of Btx-A group (P＜0.05),and on day 42-70,the value of muscle strength of 20 ug IGF-1Ab group was signficantly lower than that of 2 μg IGF-1Ab group (P＜0.05).The MOI values of the positive reaction zone changed with the same trend.Conclusion IGF-1Ab can suppress the restore of motor endplate function after injection of Btx-A.

Aim To observe the effect of endomorphin-1 (EM-1 )on TLR2 and TLR4 expressions of dendritic cells (DC)from human peripheral blood.Methods Monocytes isolated from human peripheral blood mono-nuclear cells were cultured in medium containing re-combinant human interleukin-4 and recombinant hu-man granulocyte macrophage colony stimulating factor. After six days of culture,the immature dendritic cells (imDC ) were divided into four groups,the control group (BLA group),EM-1 group,LPS group and LPS+EM-1 group.After 2 days of culture,the expres-sions of TLR2 and TLR4 were determined by fluores-cence activated cell sorter(FACS).The expressions of TLR2 and TLR4 at mRNA level in DC were detected by RT-PCR.Results The FACS results showed that the expressions of TLR2 and TLR4 in imDC were high-er,and their expressions were decreased with the mat-uration of DC.Compared with BLA group,the expres-sions of TLR2 and TLR4 in DC were down-regulated in EM-1 group (P<0.05 ).Compared with LPS group, TLR2,TLR4 on DC surface were significantly lower in LPS +EM-1 group (P <0.01 ). RT-PCR results showed that compared with BLA group,EM-1 interven-tion induced TLR2 mRNA expression was down-regula-ted significantly (P<0.01),there were no significant changes of TLR4 mRNA expression (P>0.05 ).mR-NA expressions of TLR2 and TLR4 on DC in LPS +EM-1 group were lower than those in LPS group (P<0.05 ).Conclusions EM-1 enables the down-regula-tion of the expressions of TLR2 and TLR4 on DC sur-face,the effects of EM-1 on immune function may be associated with TLR2 and TLR4 expressions on DC surface.