Background: Recurrent pregnancy loss undermines the physical and mental health of women. Recent randomized controlled trials have reported some effects of traditional Chinese medicine (TCM); however, whether various TCM methods have different effectiveness remains unclear. Objective: To comprehensively evaluate the efficacy and adverse events of TCM for patients with RPL and to explore whether various TCM methods have different effectiveness. Methods: Ten databases were searched up to May 27, 2024. The risk of bias was assessed using the RoB2 tool. The certainty of the evidence was evaluated using the grading of Recommendations, Assessment, Development, and Evaluation tool. Pairwise and network analyses were conducted using Stata 18.0. Results: A total of 47 randomized controlled trials enrolling 6678 women with RPL were included. Pairwise analysis showed that use of TCM had a significantly lower miscarriage rate (RR 0.50 [95% CI 0.45, 0.55]), lower preterm birth rate (RR 0.81 [95% CI 0.67, 0.98), and lower adverse event rate (RR 0.46 [95% CI 0.37, 0.58]). Moreover, use of TCM was associated with a higher alive-fetus rate (RR 1.21 [95% CI 1.15, 1.26]), live-birth rate (RR 1.20 [95% CI 1.15, 1.25]), and full-term rate (RR 1.37 [95% CI 1.23, 1.53]) compared with nonuse of TCM. Network analysis demonstrated that Bushenshugan combined with conventional Western medicine was ranked the best for the reduction of miscarriage rate. Discussion: Use of TCM is more likely to improve pregnancy outcomes and reduce adverse events compared with nonuse of TCM in patients with RPL. Different TCM methods have differences in reducing the miscarriage rate. The Bushenshugan method might be a potential optimal TCM therapy, but more high-quality evidence is needed to further validate and evaluate the efficacy and safety.

Objective To investigate the effects of abdominal massage combined with electroacupuncture point-through-point method on the expressions of circadian clock genes of Clock,BMAL1,PER1 and neurotransmitters contents of ACh and Glu in insomnia rats and its possible mechanism.Methods Totally 50 SD male rats were randomly divided into normal group,model group,abdominal massage group,electroacupuncture point-through-point group and combination group,with 10 rats in each group.Except for the normal group,an insomnia rat model was established by intraperitoneal injection of p-chlorophenylalanine.Abdominal massage group received abdominal massage;electroacupuncture point-through-point group was treated with flat acupuncture,"Baihui"through"Shenting","Sanyinjiao"through"Yinlingquan"(bilateral),"Shenmen"through"Neiguan"(bilateral),the electroacupuncture instrument dilatational wave,frequency of 1 Hz/20 Hz was connected;the combination group was treated with electroacupuncture through acupoints after abdominal massage;1 time/d for each treatment group,a total of 7 days.The normal group and model group were not intervened.HE staining was used to observe the pathological changes of neurons in hypothalamic tissue,the expression of Clock,BMAL1 and PER1 mRNA were detected by RT-qPCR,the expressions of Clock,BMAL1 and PER1 in hypothalamic tissue were detected by immunohistochemical staining,the expression of Clock,BMAL1 and PER1 protein in hypothalamic tissue were detected by Western blot,the contents of ACh and Glu in serum were detected by ELISA.Results Compared with the normal group,the model group rats had a longer sleep latency,shorter sleep duration,severe damage to the cellular structure of the hypothalamic tissue,and a vacuolar like change,with a decrease in the number of neuronal cells,the expressions of Clock and BMAL1 mRNA and protein in hypothalamic tissue increased,while the expressions of PER1 mRNA and protein decreased;the contents of serum ACh and Glu increased,with statistical significance(P<0.05).Compared with the model group,the abdominal massage group,electroacupuncture point-through-point group,and combination group could all shorten the sleep latency,prolong sleep duration,and improve the morphology of hypothalamic neurons,reduce the expressions of Clock and BMAL1 mRNA and protein in hypothalamic tissue,up-regulate the expressions of PER1 mRNA and protein,and reduce the contents of serum ACh and Glu,with statistical significance(P<0.05),the combination group showed the most obvious effects(P<0.05).Conclusion Abdominal massage combined with electroacupuncture point-through-point method can improve insomnia.Its mechanism may be related to the regulation of circadian clock genes Clock,BMAL1,PER1 mRNA and protein expression,as well as neurotransmitter content.

Objective To explore the funding situation and hot research directions of NSFC(National Natural Science Foundation of China)projects in the discipline of acupoints and meridians from 1991 to 2022;To provide reference for this discipline to apply for the NSFC.Methods National Natural Science Foundation of China was login in to query website.The acupoints and meridians discipline project from 1991 to 2022 were retrieved.The project leader,project name,supporting unit,province,funding category,funding amount,keywords and other information were extracted.The data were input to Excel 2023 to establish a database,and descriptive analysis of project funding situation was performed.Target keywords were extracted,and the word table was classified and uploaded to the micro-word cloud online to draw the word cloud map to analyze the research hotspots.Results From 1991 to 2022,the number of projects funded by the NSFC for acupoints and meridians was 173.The funding category was mainly general projects,and the supporting units were mainly TCM colleges and universities and scientific research institutions.The main research directions were meridian essence,acupoint-viscera/body related effects and mechanism of action,and the signal molecules and related pathways were the entry points.Conclusion From 1991 to 2022,the NSFC-funded acupoints and meridians disciplines are mainly based on general projects,mainly concentrated in scientific research institutions and TCM colleges and universities,with uneven regional distribution.The essence of meridians and collaterals,acupoints-viscera/body-related effects and mechanisms(mechanisms)are the key research directions.

ObjectiveTo explore the research status and trends of cohort studies on traditional Chinese medicine （TCM） efficacy evaluation from 2017 to 2022 and provide ideas and references for research in this field. MethodsSix databases including Pubmed， Web of Science， Embase， Scopus， Cochrane Library and CNKI were searched from January 1st， 2017 to December 31st， 2022. The total number of annual publications， journals， highly cited literatures， and keywords were quantitatively and visually analyzed by Bibliometrix. ResultsA total of 328 articles were included， which were published in 141 journals. The number of articles published in this field showed an overall upward trend， and retrospective cohort studies （282 papers， 85.98%） accounted for the largest proportion. A total of 151 cohort studies （46.04%） were conducted based on the database and showed an overall upward trend. The subjects were mainly patients with tumors （77 papers， 23.48%）， and cardiovascular and cerebrovascular diseases （64 papers， 19.51%）. The top 3 highly cited literatures mainly explore the association between TCM and survival outcome and quality of life in patients with malignant tumors. Fourteen and twenty-five high-frequency keywords were included in Chinese and English literature respectively， which formed 3 clusters such as research methods， statistical analysis and diseases. ConclusionIt was the current status to focus on retrospective cohort studies and focus on patients with tumors or cardiovascular and cerebrovascular diseases. Using observational database to conduct cohort studies of TCM efficacy evaluation could be the future research direction.

Objective:To investigate the effect of mid-ventricular obstruction (MVO) on left ventricular systolic function in patients with hypertrophic cardiomyopathy(HCM) by four-dimensional automatic left ventricular quantitation technology(4D Auto LVQ).Methods:Fifty-seven hypertrophic obstructive cardiomyopathy patients were selected from December 2020 to October 2022 in the First Affiliated Hospital of Zhengzhou University. According to the presence of MVO, HCM patients were divided into two groups: HCM 1 group, HCM without MVO ( n=34); HCM 2 group, HCM with MVO ( n=23). In addition, 25 healthy subjects in the same period were selected as the control group. Conventional ultrasound parameters were collected, and 4D Auto LVQ technology was used to obtain the mechanical parameters of left ventricular myocardium, including left ventricular longitudinal strain (GLS), circumferential strain (GCS), area strain (GAS), radial strain (GRS), segmental longitudinal strain (SLS) and area strain (SAS). The differences of these parameters among the three groups were compared. Results:①Compared with the control group, the thickness of the maximum basal segment of interventricular septum, the thickness of the middle segment of the maximum interventricular septum, the thickness of the apical segment of the interventricular septum, the thickness of the left ventricular posterior wall and left atrium diameter were significantly increased. Six-minute walk distance and the left ventricular end-diastolic diameter was decreased in the two groups of HCM(all P<0.05). Left ventricular outflow tract gradients in HCM 1 group was higher than HCM 2 group( P<0.05), but there was no significant difference in left ventricular ejection fraction among the three groups( P>0.05). There was significant difference in the incidence of left ventricular apical aneurysm among the three groups( P<0.05). ②Compared with the control group, the GLS in both HCM groups was lower, and it was lower in the HCM 2 group than in the HCM 1 group(all P<0.05) the GRS and GAS in both HCM groups were lower than in the control group ( P<0.05), and there was no significant difference between the two groups of HCM, and there was no significant difference in GCS among the three groups(all P>0.05). ③Compared with the control group, the SLS of basal segment, middle segment, apical cap, posterior septum, inferior wall and lateral wall in HCM group were significantly lower than those in control group. The SLS of apical segment of posterior septum, anterior septum, anterior wall, posterior wall, inferior wall and apical segment of posterior septum, lateral wall and inferior wall in HCM 2 group were significantly lower than HCM 1 group(all P<0.05), but there was no significant difference in SLS of posterior septum, anterior septum, anterior wall, lateral wall and inferior wall between the two groups(all P>0.05). ④Compared with the control group, the SAS of posterior septal basal segment, middle segment, anterior septal middle segment, anterior wall basal segment, middle segment, apical segment, lateral wall basal segment, middle segment, apical segment, posterior wall basal segment, middle segment, inferior wall basal segment, middle segment and apical cap in HCM groups were significantly lower than the control group(all P<0.05), but there was no significant difference in SAS between the two groups of HCM( P>0.05). Conclusions:4D Auto LVQ can quantitatively evaluate the damage of MVO on the left ventricular systolic function in patients with HCM, especially for the evaluation of local myocardial function damage in the medial segment and apical segment.

Objective:To explore the efficacy, safety and possible brain network mechanisms of individualized targeted robot assisted Stanford accelerated intelligent neuromodulation therapy (SAINT).Methods:This was a small-sample, open-label study including 15 depressed patients with suicidal ideation. All participants were treated with SAINT in combination with SNRIs. The stimulation target was localized to the region of the left dorsolateral prefrontal cortex (DLPFC) that showed the most negative functional connectivity with the subgenual anterior cingulate cortex (sgACC) based on fMRI data. Stimulation sessions were delivered hourly. Ten sessions were applied per day (18, 000 pulses/day) for 5 consecutive days (90, 000 pulses in total). Stimulation was delivered at 90% resting motor threshold. The changes of functional connectivity of brain networks in various brain regions before and after treatment were compared and analyzed by rest software and functional connectivity analysis based on seed points. The Beck Suicidal Ideation Scale Chinese Version (BSI-CV), HAMD 17, and MADRS were used to assess the suicidal ideation and depressive symptoms at baseline, post treatment, 15 days after treatment, and 30 days after treatment. Statistical analysis was performed using repeated measurements of ANOVA and paired t-tests. Results:(1) After 5-day treatment, individual′s BSI-CV score decreased significantly ( F=38.77, P<0.01), and their average score decreased by 11.80±1.17 (95 %CI=8.19-15.41), with a response rate of 86.67%. SAINT was well tolerated, and there were no significant side effects on individual′s cognitive function. (2) After treatment, patient′s MADRS score decreased significantly at all follow-up assessments ( F=306.97, P<0.01), and the average score decreased by 22.53±1.10 (95 %CI=19.15-25.91) after 5-day treatment, with a response rate of 93.33%. After 15 days and 30 days, the remission and response rates of treatment were 53.33%, 100.00%, 93.33% and 100.00%, respectively. (3) The functional network connectivity after individualized targeted robot assisted SAINT therapy showed significant improvement between sgACC, frontal lobe, temporal lobe, and parietal lobe. Conclusion:Individualized targeted robot assisted SAINT therapy showed satisfactory efficacy and safety in the reduction of suicidal ideation and depressive symptoms, and also improve the functional network connectivity of the injured brain network. Meanwhile, large-sample, randomized, and double-blind controlled studies are warranted to confirm the findings of the current study.

Objective:To explore the efficacy, safety and possible brain network mechanisms of individualized targeted robot assisted Stanford accelerated intelligent neuromodulation therapy (SAINT).Methods:This was a small-sample, open-label study including 15 depressed patients with suicidal ideation. All participants were treated with SAINT in combination with SNRIs. The stimulation target was localized to the region of the left dorsolateral prefrontal cortex (DLPFC) that showed the most negative functional connectivity with the subgenual anterior cingulate cortex (sgACC) based on fMRI data. Stimulation sessions were delivered hourly. Ten sessions were applied per day (18, 000 pulses/day) for 5 consecutive days (90, 000 pulses in total). Stimulation was delivered at 90% resting motor threshold. The changes of functional connectivity of brain networks in various brain regions before and after treatment were compared and analyzed by rest software and functional connectivity analysis based on seed points. The Beck Suicidal Ideation Scale Chinese Version (BSI-CV), HAMD 17, and MADRS were used to assess the suicidal ideation and depressive symptoms at baseline, post treatment, 15 days after treatment, and 30 days after treatment. Statistical analysis was performed using repeated measurements of ANOVA and paired t-tests. Results:(1) After 5-day treatment, individual′s BSI-CV score decreased significantly ( F=38.77, P<0.01), and their average score decreased by 11.80±1.17 (95 %CI=8.19-15.41), with a response rate of 86.67%. SAINT was well tolerated, and there were no significant side effects on individual′s cognitive function. (2) After treatment, patient′s MADRS score decreased significantly at all follow-up assessments ( F=306.97, P<0.01), and the average score decreased by 22.53±1.10 (95 %CI=19.15-25.91) after 5-day treatment, with a response rate of 93.33%. After 15 days and 30 days, the remission and response rates of treatment were 53.33%, 100.00%, 93.33% and 100.00%, respectively. (3) The functional network connectivity after individualized targeted robot assisted SAINT therapy showed significant improvement between sgACC, frontal lobe, temporal lobe, and parietal lobe. Conclusion:Individualized targeted robot assisted SAINT therapy showed satisfactory efficacy and safety in the reduction of suicidal ideation and depressive symptoms, and also improve the functional network connectivity of the injured brain network. Meanwhile, large-sample, randomized, and double-blind controlled studies are warranted to confirm the findings of the current study.

BACKGROUND: Polymorphism of CYP3A5 gene can significantly affect the blood concentration of tacrolimus in the early period after kidney transplantation. Many studies in China are limited to the early 3 months after kidney transplantation with no concern on the long-term effect of tacrolimus in recipients. OBJECTIVE: To investigate the relationship between the polymorphism of CYP3A5 gene and tacrolimus concentration/dose (C0/D) in kidney transplant recipients, and to compare the differences among different genotypes, so as to provide an individualized drug regimen of tacrolimus after kidney transplantation. METHODS: Sixty-five adult recipients who underwent kidney transplantation and postoperative administration of tacrolimus (FK506) + mycophenolate mofetil (MMF) + prednisone (Pred) immunosuppressive therapy were divided into three groups according to their CYP3A5 genotypes detected preoperatively: CYP3A5*1/*1, *1/*3, and *3/*3 groups. The whole blood concentration of tacrolimus was monitored in all the recipients, and C0/D value was recorded in each group at different time points after surgery. The study protocol was in line with the ethical requirements of Air Force Hospital of Northern Theater Command. RESULTS AND CONCLUSION: There were 6, 25 and 34 recipients of CYP3A5*1/*1, *1/*3 and *3/*3, respectively. The C0/D value of tacrolimus in the CYP3A5*1/*1 and *1/*3 groups was significantly lower than that in the CYP3A5*3/*3 group (P < 0.05). At 7 and 14 days after surgery, the C0/D value of tacrolimus in the CYP3A5*1/*1 group was lower than that in the CYP3A5*1/*3 group (P=0.028, P=0.034). In the CYP3A5*1/*1 group, the C0/D value of tacrolimus at 7 days after surgery was significantly lower than that at 6 months and 1 year after surgery (P=0.35, P=0.41). In the CYP3A5*1/*3 group, the C0/ D value of tacrolimus at 7 days after surgery was significantly lower than that at 3 months, 6 months and 1 year after surgery (P=0.029, P=0.07, P < 0.01), and that at 14 days and 1 month after surgery was significantly lower than that at 6 months and 1 year after surgery (P=0.04, P=0.39). In the CYP3A5*3/*3 group, the C0/D value of tacrolimus at 7 days after surgery was significantly lower than that at 3 months, 6 months and 1 year after surgery (P=0.029, P=0.03), and that at 14 days after surgery was significantly lower than that at 6 months and 1 year after surgery (P=0.022). Overall findings indicate that the polymorphism of CYP3A5 gene has a significant effect on the C0/D value of tacrolimus in kidney transplant recipients, which can be maintained for a long-term stable period after transplantation. For CYP3A5*1/*1 and *1/*3 recipients, the metabolism of tacrolimus is faster in the early stage, and the dosage of tacrolimus should be increased to maintain the target blood concentration, whereas for CYP3A5*1/*3 recipients, the dosage of tacrolimus may be moderately less than the former and the drug reduction rate should be slowed down in the later stage. CYP3A5*3/*3 recipients have a slow metabolism of tacrolimus, and should be given a small dose in the early stage, and the reduction rate should be accelerated in the later stage.

Objective To identify the differences inneuropsychological characteristics between amnestic(AMCI)and vascular mild cognitive impairment(VMCI).Methods Totally 297 old community residents with mild cognitive impairment(MCI)were divided into amnestic MCI(AMCI)and vascular MCI(VMCI)subgroup from Guangzhou MCI prevalence survey.The elderly with MCI were interviewed and tested with the Chinese version of Montreal Cognitive Assessment(MoCA),the Mini-Mental state examination(MMSE),Auditory Verbal Learning Test(AVLT),the Clinical Dementia Rating scale(CDR),Functional Activity Questionnaire(FAQ),the Modified Hachinski Ischemic Scale(M-HIS),Center for Epidemiologic Studies(CES-DC)to evaluate neuropsychological characteristics.Results AMCI versus VMCI group showed that the total scores of MoCA were(9.63±5.17 vs.9.98±6.02),total scores of MMSE were(16.90±4.84 vs.16.90±6.19),AVLT immediate memory was(2.35±1.39 vs.2.91±1.84),AVLT delayed recall was(2.23±2.09 vs.2.47±2.20),AVLT delayed recognition was(7.33±3.98 vs.6.85±4.02)and total scores of CDR(0.5 vs.0.5),with no differences between the 2 groups(all P>0.05).Based on MoCA survey,AMCI versus VMCI group showed statistically significant differences(all P<0.05)in parameters of visual space and execution(0.71±1.02 vs.0.92±1.26),language function(0.34±0.56 vs.0.50±0.80)and abstract thinking(0.25±0.49 vs.0.15±0.43),but based on MMSE survey,no difference was found in the various cognitive domains between the two groups.The AMCI versus VMCI group showed statistically significant differences(all P<0.05)in parameters of CES-DC scale(1.75±4.27 vs.2.76±6.72),FAQ scale(4.42±4.66 vs.8.71±7.03),M-HIS scale(0.40±0.64 vs.7.59±3.53).Conclusions There is no significant difference in general cognitive impairment between AMCI and VMCI,but the visual space and execution,language function are more impaired in AMCI than VMCI,and the abstract thinking,social function are more impaired with more depressive symptoms in VMCI than in AMCI.

BACKGROUND: Currently, the researches on knee plaster immobilization paralysis animal models are popular in the world, but there are some insufficiencies with the knee paralysis animals, for example, poor animal selection, inappropriate plaster selection and pure gypsum instability, which affect the subsequent results.
OBJECTIVE: To establish a rabbit model of knee paralysis by the knee fixation with plaster casts and wire.
METHODS: A total of 20 New Zealand white rabbits were randomly divided into two groups. Models of right knee paralysis were established and fixed by plaster casts and wire. Normal controls were considered as the control group. At 8 weeks after fixation, right knee and pathologic histology were observed in the right knee.
RESULTS AND CONCLUSION: The knee joints were translucent, smooth, and shiny, without the cartilage defect in the control group, and the cartilaginous elasticity and rigidity were good, and the arrangement of chondrocytes was normal. There were no inflammatory infiltrations in the articular capsule of the normal rabbits. In the model group, the knee joint was matt and opaque. Articular cartilage became thin, and showed poor elasticity. The cartilages were degenerated. Articular surface was rough, and had defects. There were smal amount of joint fluid or no joint fluid. Cartilage cel s shrank or disappeared, and the number of cartilage cel s reduced with degeneration and necrosis. Subchondral bone became sclerosis with trabecular bone of hyperplasia. The arrangement of cartilage cel s was disordered, with hyalinization and synovial vil ous hypertrophy. Cel clustering phenomenon was seen. There were a large number of lymphocytes, plasma cel s and neutrophil infiltration in cartilages. The typical pathological changes of the knee paralysis present in the rabbit cartilage. These results demonstrate that the rabbit model of knee paralysis can be successful y established by using fixation method with plaster casts and wire, which has the advantages of simple operation, strong fixation and no injury.