Objective: To analyze the association between dietary diversity and cognitive function among the elderly using group-based trajectory model, so as to provide the basis for formulating dietary intervention strategies to prevent cognitive impairment. Methods: Based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) project, demographic information, lifestyle behaviors, psychological well-being, and activities of daily living of elderly individuals aged ≥65 years from 2008 to 2018 were collected. Dietary diversity was assessed using a food frequency questionnaire, with a score of <7 points defined as low dietary diversity. Cognitive function was evaluated using the Chinese version of the Mini-Mental State Examination (MMSE). A group-based trajectory model was established based on cognitive function scores from 2008 to 2018 to analyze the trajectories of cognitive function change. The association between dietary diversity and cognitive function was analyzed using a multinomial logistic regression model. Results: A total of 1 613 individuals were collected, with a median age was 72.00 (interquartile range, 10.00) years. There were 810 males (50.22%) and 803 females (49.78%). The group-based trajectory model analysis categorized the participants into three groups: the low-level normal group, the high-level normal group, and the slow-then-rapid decline group, comprising 796 (49.35%), 585 (36.27%), and 232 (14.38%) individuals, respectively. Among these groups, the numbers of individuals with low dietary diversity were 497 (62.44%), 311 (53.16%), and 166 (71.55%), respectively, with a statistically significant difference (P<0.05). Multinomial logistic regression analysis showed that after adjusting for demographic information, lifestyle behaviors, psychological well-being, and activities of daily living, compared with the high-level normal group, low dietary diversity was statistically associated with cognitive function in the slow-then-rapid decline group (OR=1.622, 95%CI: 1.103-2.384). Conclusion Low dietary diversity may increase the risk of cognitive impairment among the elderly.

In recent years， there have been both achievements and criticisms in using the methods of evidence-based medicine to evaluate the efficacy of traditional Chinese medicine （TCM）， which is mainly due to the differences between TCM and Western medicine. To facilitate the clinical evidence-based evaluation in TCM， this paper analyzes the challenges faced in TCM clinical evaluation， particularly in the diagnosis， clinical intervention， and efficacy assessment methods. Considering the current state of TCM clinical evaluation and our clinical research experience， we believe that establishing and refining the TCM disease-syndrome diagnostic system is a prerequisite for the practice of clinical evidence-based evaluation in TCM. Furthermore， this paper discusses the specific connotation， development， and challenges of the disease-syndrome diagnostic system， especially the choice of TCM disease name or modern medical disease name in this system. Then， the clinical application scenarios are expounded from ''TCM disease name + syndrome differentiation'' and ''Western medicine disease name + syndrome differentiation''. Moreover， this paper proposed solutions for practical issues such as the standardization of disease and syndrome diagnosis， selection of clinical evaluation methods， and application of evidence-based approaches in clinical evaluation. Establishing the criteria for the disease-syndrome diagnostic system is crucial for the determination of clinical intervention regimen， the selection of clinical research methods， and the establishment of evaluation indicators， which are essential for generating high-quality clinical evidence. To sum up， this paper reviews the development and current situation of the disease-syndrome diagnostic system and proposes an exploratory approach for the standardization and application of this system in clinical evidence-based evaluation. This approach aims to facilitate the integration of TCM with modern clinical practice， thereby achieving standardized evaluation of TCM efficacy and deepening the integration of TCM with evidence-based medicine.

BACKGROUND:Our previous studies found that the polypeptide of Cornus cervi Colla can promote bone growth,which has a good application prospect in the treatment of bone diseases.However,how Cornus cervi Colla works in the body and the principle are not clear. OBJECTIVE:To study the in vivo distribution and tracing of Cornus cervi Colla using fluorescence labeling and tracer technique. METHODS:Cornus cervi Colla was fluorescently labeled using fluorescein isothiocyanate,and the labeling results were detected by fluorescence imaging and UV spectral scanning.Successfully labeled Cornus cervi Colla was injected into mice by gavage,and the absorption of Cornus cervi Colla into blood was detected by laser confocal microscopy,and the distribution of Cornus cervi Colla in mice was detected by small animal in vivo imager.The distribution of Cornus cervi Colla in the mice was detected by laser confocal microscopy.Samples were taken from serum and bone at the time of the strongest fluorescence,and gel electrophoresis was carried out on serum and bone tissue protein solutions,and the components of Cornus cervi Colla absorbed into target organs were determined by secondary mass spectrometry. RESULTS AND CONCLUSION:The fluorescent markers were successfully separated by dextran gel chromatography,and the fluorescence imaging and ultraviolet spectrum scanning proved that the labeling was successful,and the fluorescence substitution degree of FITC-labeled Cornus cervi Colla was 0.953%.The fluorescence intensity of the components of Cornus cervi Colla in the blood showed that Cornus cervi Colla was most distributed in serum after oral administration for 2 hours.The fluorescence images of mice at different times were the same as those of bilateral femur and tibia,indicating that Cornus cervi Colla could play a role by entering the bone.Compared with UniProt database,secondary mass spectrometry showed that the peptide was a characteristic fragment of decorin.It is proved that decorin in Cornus cervi Colla can enter the bone to play a therapeutic role.

BACKGROUND:Osteonecrosis of the femoral head is a common and disabling disease,which is mainly characterized by microcirculation disorders and bone cell metabolism disorders.Luzhongjiangu decoction was developed by Shandong Academy of Chinese Medicine and used in the form of soup in the clinic,which has good efficacy in the treatment of osteonecrosis of the femoral head.However,its mechanism of action has not been clarified. OBJECTIVE:To study the effect mechanism of Luzhongjiangu decoction on intestinal flora in rats with osteonecrosis of the femoral head based on 16S rDNA sequencing technique. METHODS:The model of osteonecrosis of the femoral head was established in Wistar rats by intragastric administration of retinoic acid.The therapeutic effect of Luzhongjiangu decoction was evaluated by serum hormone,bone histopathology and serum hormone levels.16s rDNA sequencing technique was used to detect the intestinal flora of rats in the blank control group,model group and middle-dose Luzhongjiangu decoction group.The corresponding library was constructed and OTU clustering and microbial community diversity and abundance analysis were carried out to determine the composition of intestinal flora and the changes of species and diversity among groups. RESULTS AND CONCLUSION:Luzhongjiangu decoction could significantly increase the expression of osteocalcin,osteopontin and other osteogenic related factors,alleviate the destruction of bone trabeculae,increase bone mineral density,and had a significant therapeutic effect on osteonecrosis of the femoral head,of which the middle dose group showed the most significant effect.The results of intestinal flora sequencing showed that Luzhongjiangu decoction improved the flora disorder of rats with osteonecrosis of the femoral head to some extent,and screened out different colonies such as Bacillus,Desulfurizans,Desulfurization,Isobacteria,Bifidobacterium and so on;it could up-regulate the abundance of beneficial bacteria such as Bifidobacterium,down-regulate the abundance of harmful bacteria such as Desulfovibrio,and improve the structure of intestinal flora.Functional prediction analysis indicated that Luzhongjiangu decoction could mainly affect amino acid metabolism and energy metabolism.Correlation analysis showed that the differential bacteria of Bifidobacterium and Intestinimonas in the middle dose group of Luzhongjiangu decoction were positively correlated with vitamin D3,estradiol and calcitonin,and negatively correlated with prostaglandin E2.In the model group,Escherichia-Shigella,Desulfovibrio,Globicatella and Streptococcus were positively correlated with prostaglandin E2 and negatively correlated with vitamin D3,estradiol and calcitonin.To conclude,Luzhongjiangu decoction may play a role in the treatment of osteonecrosis of the femoral head by regulating the structure of intestinal flora,up-regulating the abundance of beneficial bacteria and affecting the secretion of vitamin D3,estradiol,calcitonin and prostaglandin E2.

Objective To systematically evaluate the efficacy of Xixian Tongshuan Capsules/Pills in the treatment of acute ischemic stroke(AIS).Methods Literature about Xixian Tongshuan Preparation combined with conventional Western medicine for the treatment of AIS was retrieved from CNKI,SinoMed,VIP,Wanfang Data,PubMed,Medline,Embase,Cochrane Library and Web of Science from establishment of the databases to February 28,2023.Meta-analysis was conducted for the studies that could be quantitatively analyzed.The effective rate and response indicators were combined.Results A total of 7 articles were included for Meta-analysis.Results showed that there was statistical difference in the effective rate(RR=0.34,95%CI[0.23,0.51],P<0.01),NIHSS score(MD=-2.90,95%CI[-3.74,-2.06],P<0.01),BI score(MD=-10.08,95%CI[-13.47,-6.68],P<0.01),FIB(MD=-1.18,95%CI[-1.59,-0.77],P<0.01)of Xixian Tongshuan Preparation combined with conventional Western medicine for the treatment of AIS.There was no statistical difference in IL-6(MD=-15.4,95%CI[-33.3,2.49],P=0.09).There was no statistical difference in the effects of different dosage forms and treatment courses on the effective rate and NIHSS score.Conclusion The combination of Xixian Tongshuan Capsules/Pills could better improve the NIHSS and BI scores of patients with AIS,recovery the neurological function,and reduce the risk of blood hypercoagulability by reducing FIB content,with good safety.

Objective:To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism.Methods:The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining.Results:Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP ( P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower ( P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group ( P all<0.05). Conclusions:TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.

Objective By observing the effects of"three methods and three points"tuina technique on the expression of interleukin-17F(IL-17F),interleukin-17 receptor C(IL-17RC),activator 1 of nuclear transcription factor-κB(Act1),tumour necrosis factor receptor-associated factor 6(TRAF6)and M1 microglial cell expression in the spinal dorsal horn of rats with mild chronic compressive injury(minor CCI)model,we explored the immediate analgesic mechanism of tuina on peripheral neuropathic pain(pNP).Methods Thirty-six SD rats were divided into the sham group,the model group and the tuina group according to the random number method,twelve rats in each group,and the minor CCI model was replicated by ligating the right sciatic nerve.The rats in the tuina group were subjected to pointing,plucking and kneading at the BL37,BL57 and GB34 points on the affected side using a tuina simulator,while the sham group and the model group were only grasped and restrained,and were intervened for one time.The mechanical pain test and cold plate test were used to evaluate the response of rats to mechanical stimulation and cold stimulation after immediate intervention.The protein expression of IL-17F and TRAF6 in the spinal dorsal horn of rats in each group was detected by Western blotting.The mRNA expression of IL-17F,IL-17RC,Act1 and TRAF6 in the spinal dorsal horn of rats in each group was detected by real-time PCR.The average fluorescence intensity of M1 microglia in the spinal dorsal horn of rats in each group was detected by immunofluorescence.Results Behavioral results showed that before intervention,compared with the sham group,paw mechanical withdraw threshold(PMWT)decreased and cold sensitivity threshold(CST)increased in the model group and the tuina group;after tuina intervention,PMWT in the tuina group was increased,and CST was decreased compared with the model group;after intervention,PMWT in the tuina group was increased,while CST was decreased(P＜0.05).RT-PCR results showed that compared with the sham group,mRNA expression levels of IL-17F,IL-17RC,TRAF6 and Act1 in the spinal dorsal horn of the model group were increased;compared with model group,the mRNA expression levels of above indexes in the tuina group were decreased(P＜0.05).Western boltting results showed that compared with the sham group,the expression levels of IL-17F and TRAF6 protein in the spinal dorsal horn of the model group were increased;compared with the model group,the expression levels of IL-17F and TRAF6 protein in the tuina group decreased(P＜O.05).Immunofluorescence results showed that the mean fluorescence intensity of CD40 in the spinal dorsal horn of model group was enhanced compared with the sham group;compared with the model group,the mean fluorescence intensity of CD40 in the tuina group was decreased(P＜0.05).Conclusion The"three methods and three points"tuina technique can produce immediate analgesia by inhibiting the expression of IL-17F,IL-17RC,Act1,TRAF6 and the activation of M1 microglia in the dorsal horn of the spinal cord after one intervention.

Objective To systematically evaluate the efficacy and safety of compound Duzhong Jiangu granules in the treatment of knee osteoarthritis.Methods According to PICOS principle,literature retrieval was carried out in CNKI,SinoMed,VIP,WanFang,PubMed,Medline,Embase and Cochrane Library,and the retrieval time was up to October 2023.Meta-analysis was performed on quan-tifiable studies,and the effective rate and efficacy indicators were combined.Results A total of 5 articles were included for Meta-anal-ysis.The effective rate of compound guzhong Jiangu granules was higher than that of control group,the difference was statistically signifi-cant(RR=1.12,95％CI:1.07-1.18,P＜0.001).Compared with the control group,there were significant differences in pain or discomfort scores during bed rest at night,standing from seat score,maximum walking distance score,getting off standard ladder score,walking on uneven road score and WOMAC score between compound duzhong jiangu granules and the control group(P＜0.01).There were no significant differences in improving morning stiffness or pain after getting up,boarding standard ladder score and joint function ef-ficacy score between compound Duzhong Jiangu Granules and control group(P＞0.05).There were no serious adverse events were repor-ted in the included studies.Conclusion Combined with compound guzhong jiangu granules can improve the therapeutic effect of knee os-teoarthritis,relieve a mild to moderate pain to a certain extent,and promote the recovery of joint function,but it is not good for improving morning stiffness,so it is recommended for early combined treatment with good safety.

Objective To compare cortical inhibition(CI)function between patients with schizophrenia and depression,and to explore the correlation between CI function and clinical symptoms.Methods A total of 35 first episode schizophrenia(FES)patients,41 depression patients(21 with first episode depression,20 with recurrent depression),and 35 healthy controls(HC)were recruited.The positive and negative syndrome scale(PANSS)was used to assess symptoms in FES patients,while the 17-item Hamilton depression scale(HAMD-17)and Hamilton anxiety scale(HAMA)were used to assess symptoms in depression patients.All participants'cortical inhibition and excitation measures were examined using single or paired pulses transcranial magnetic stimulation.Analysis of covariance/generalized linear model was employed to compare cortical inhibition and excitation measures among groups including age,gender,and medication status as covariates.The correlations between cortical inhibition and excitation measures and clinical symptoms were analyzed.Results The cortical silent period(CSP)in FES group was longer than that in control group and depression group[(92.08±35.43)ms vs.(70.27±22.12)ms vs.(70.81±29.29)ms,P<0.05].Depression group was further divided into first episode depression(FED)and recurrent depression(RD)subgroups.The short-interval cortical inhibition(SICI)was weaker in FED group than in the RD group and the control group(0.76±0.44 vs.0.43±0.32 vs.0.45±0.20,P<0.05).In FED group,CSP was negatively correlated with the general symptom score of PANSS(r=-0.544,P<0.001),and SICI was negatively correlated with the negative symptom score of PANSS(r=-0.501,P=0.005).In the FED group,SICI was positively correlated with HAMD-17 score(r=0.605,P=0.028).Conclusion Both FES patients and FED patients exhibit abnormal CI.There are distinct characteristics between FES and FED.FES patients exhibit prolonged CSP,while FED patients exhibit decreased SICI.The abnormal CI in FES and FED are correlated with their clinical symptoms.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.