Intestinal flora imbalance is closely related to the pathogenesis of rheumatoid arthritis (RA). The existing studies have explored the monomer components such as tripterygium glycosides, total glycosides of Chaenomeles speciosa, and triterpenoid saponins of Clematis, Chinese materia medica such as Tripterygium wilfordii, Caulis Sinomenii, Radix Paeoniae Alba, Fructus Gardeniae, Fructus Chebulae, Radix Ginseng, Radix et Rhizoma Rhei, Rhizoma Atractylodis Macrocephalae, Pterostilbene, and Ginger, as well as the mechanisms of Danggui Sini Decoction, Danggui Niantong Decoction, Duhuo Jisheng Decoction, Yunpi Jiedu Tongluo Qushi Decoction, Qingre Huoxue Decoction, Compound Fengshining, Qingre Yangyin Chushi Decoction, Aconitum Decoction, Zhijing Powder, Jinwu Jiangu Capsule, and Fermented Chinese Medicine Qushi Chubi Decoction in intervening RA by regulating intestinal flora, suggesting that Chinese materia medica can restore intestinal homeostasis, reduce joint inflammation and play a role in the prevention and treatment of RA by regulating immune response, improving intestinal mucosal barrier and regulating intestinal metabolites.

Background With the rapid industrialization, cadmium has become a primary heavy metal pollutant in cultivated land soil in China, which seriously affects human health. Previous studies have found that cadmium exposure associates with cognitive dysfunction in individuals, but there is a lack of research on the mechanism of cadmium exposure associated cognitive impairment in offspring in early life which is more vulnerable to various toxins and crucial for development of the neuro. Objective To explore the potential mechanism of brain-derived neurotrophic factor/tyrosine kinase receptor B (BDNF-TrkB) signaling pathway in cognitive dysfunction in mice after cadmium exposure in early-life. Methods Twelve 8-week-old C57BL/6 pregnant mice were randomly divided into 2 groups, namely control group and cadmium exposure group, with 6 mice in each group. The exposure period was from pregnancy day 4.5 to lactation day 21 (E4.5-P21), during which distilled water or cadmium chloride solution (2.5 mg·kg⁻¹·d⁻¹) was given. After lactation, the offspring of the control group and the cadmium exposure group were given distilled water until 8 weeks of age. Then the toxicity effects of cadmium exposure on mice were evaluated by body weight and selected biochemical indicators. The cadmium content in brain was detected and the learning and memory ability was tested by Y maze and Morris water maze to evaluate cognitive function of offspring mice. Histopathological changes of the hippocampus were observed after Nissl staining and Golgi staining. The mRNA and protein expression levels of the BDNF-TrkB pathway and synapse were detected by real-time quantitative PCR (qPCR) and Western blot. Results Compared with the control group, no significant change was found in body weight, liver or kidney function in the cadmium exposure group (P> 0.05). However, compared with the control group, the cadmium content in brain was increased in the cadmium exposure group (P<0.001). The behavioral changes associated with cognitive dysfunction were positive in the cadmium exposure group (all P<0.05). The histopathological observation after Nissl staining showed abnormal tissue structure, decreased number of neurons and increased karyopyknosis in the cadmium exposure group (P<0.01).The spine density of Golgi staining was decreased in the cadmium exposure group (P<0.001). The BDNF-TrkB pathway-related mRNA and the synapse-related mRNA in the hippocampus were reduced in the cadmium exposure group (all P<0.05). The expression levels of BDNF-TrkB pathway-related proteins and synapse-related proteins in the hippocampus were also reduced in the cadmium exposure group (P<0.05). Conclusion Early-life cadmium exposure may induce synaptic dysplasia and lead to cognitive dysfunction by down-regulating the BDNF-TrkB signaling pathway in mice.

The eutR gene deletion mutant of Salmonella enteritidis was successfully constructed by homologous recombination.Through the study of its biochemical characteristics,motility,resist-ance to stress in vitro and survival ability in RAW 264.7 cells,it was found that the biochemical characteristics and motility of the eutR gene deletion mutant of Salmonella enteritidis had no sig-nificant change compared with the wild type of Salmonella enteritidis.The ability of eutR gene de-letion strain of Salmonella enteritidis to resist acid,alkali and oxidation was significantly reduced,while the ability to resist heat was not significantly changed;the survival ability of eutR gene dele-tion strain in RAW 264.7 cells was significantly reduced compared with the wild type.In order to further analyze the effect of eutR gene on the expression of virulence factors of Salmonella enterit-idis,the relative expression levels of invH,ssav,ssrA,xthA,orf245,sodC,lrp,mrr1 and hflk virulence genes of the deletion strain and the wild strain were detected by SYBR Green PCR.It was found that the expression of the virulence factors mentioned above in the eutR gene deletion strain of Salmonella enteritidis was significantly down-regulated compared with that in the wild-type strain.The LD50 of the eutR gene-deleted strain of Salmonella enteritidis was determined by ani-mal experiments,and the results showed that the LD50 of the eutR gene-deleted strain was higher than that of the wild-type strain,indicating that the eutR gene could affect the virulence of Salmonella.This study clarified the effect of eutR gene on the survival ability,some biological characteristics and virulence of Salmonella enteritidis in macrophages,and provided a new gene knockout target for the development of attenuated Salmonella enteritidis genetic engineering vac-cine.

TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.

【Objective】 To investigate the inhibitory effect of BFD-6b on colorectal cancer cell growth and its preliminary mechanism. 【Methods】 The inhibitory effect of BFD-6b on the growth of various tumor cells （SW480， MCF-7， T47D， SMMC-7721， BEL-7402， 97H， SK-HEP-1， H460， H1299， A549， MS751， and HELA） was investigated by MTT assay； the effect of BFD-6b on apoptosis and cell cycle was detected by flow cytometry； the effect of BFD-6b on the expressions of cell cycle-related proteins and apoptosis-related proteins was examined by Western blotting. 【Results】 BFD-6b inhibited the proliferation of different cancer cells such as SW480， MCF-7， H460， H1299， A549， and HELA. Among all of them， SW480 cells were most sensitive to BFD-6b， and the IC50 value was 7.09 μmol/L. Furthermore， BFD-6b could inhibit the growth of another three colorectal cell （SW620， Lovo， and HCT116 cells）； the IC50 values were 7.23， 8.08 and 8.96 μmol/L， respectively. BFD-6b could downregulate the amount of cyclinD1， cyclinE， and cell cycle-dependent kinase CDC2， thereby arresting the cell cycle at G1 phase. Also， BFD-6b downregulated the expressions of anti-apoptotic proteins Mcl-1 and Bcl-2， and upregulated the expressions of pro-apoptotic proteins BAK and BAX， thus inducing apoptosis of SW480 cells. 【Conclusion】 BFD-6b arrests SW480 cells at G1 phase by downregulating the expressions of cyclinD1， cyclinE and CDC2， and induces SW480 cell apoptosis by downregulating the expressions of Mcl-1 and Bcl-2 and upregulating the expressions of BAK and BAX， thereby inhibiting the proliferation of colorectal cancer SW480 cells.

Objective:To explore the attitudes of Chinese medical students toward the elderly and their willingness to practice in geriatrics, and to investigate the influence of geriatrics education on their attitudes.Methods:Medical students studying diagnostics in four medical universities were enrolled in a cross-sectional survey and, for the intervention study, graduate trainees from non-geriatrics specialties taking a geriatrics course were interviewed before and after the course.An electronic questionnaire was used to collect general information, the experience of interacting with the elderly, attitudes towards the elderly and the willingness to develop careers in geriatric medicine.Changes in attitudes towards the elderly and their willingness to practice in geriatrics before and after the 40-hour geriatric medicine course were compared.Results:A total of 648 medical students completed the cross-sectional survey, with the highest score in compassion for the elderly(3.54±0.54)and the lowest score for medical services for elderly patients(3.36±0.78). Only 2.2%(14/648)of the students showed strong interest in geriatric medicine.The results of the intervention from 42 graduate trainees showed that the average scores of revised Geriatric Attitude Scale(r-GAS)were 3.80±0.43 and 3.92±0.40 before and after the course, respectively, and the difference was statistically significant( t=2.148, P=0.038). At the end of the course, 7 trainees(16.7%, 7/42)showed great interest in geriatrics, significantly different from 2 trainees(4.8%, 2/42)before the course( χ2=8.211, P=0.025). Conclusions:Chinese medical students show a serious lack of interest in geriatrics, and geriatrics education can improve their attitudes towards the elderly and their willingness to work in geriatrics.With the rapid population aging in China, it is urgent to strengthen the education of geriatric medicine.

Objective:To quantitatively evaluate the left ventricular myocardial strains and global myocardial work indices in severe aortic stenosis(AS) patients with preserved left ventricular ejection fraction (LVEF) undergoing transcatheter aortic valve implantation (TAVI) by using two-dimensional speckle tracking imaging (2D-STI) technology and pressure-strain loop (PSL).Methods:Twenty patients undergoing TAVI from January to November 2020 in Cardiovascular Hospital of Xiamen University were selected as the TAVI group, and 20 healthy volunteers (with the matched gender, age) were selected as the control group at the same period. Left ventricular global longitudinal strain (GLS), endocardial, middle, epicardial myocardial longitudinal strain (LSendo, LSmid, LSepi) were measured by 2D-STI. The correlation between aortic pressure and the left ventricular systolic pressure invasively measured by cardiac catheterization, and blood pressure and the left ventricular systolic pressure non-invasively measured by peripheral brachial artery systolic blood pressure combined with Doppler-derived mean aortic gradient was separately compared. The non-invasive PSL was used to evaluate the global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). The differences of the myocardial strains and myocardial work indices between the two groups, including controls, patients with preoperation, 1 week and 3 months after TAVI, were compared.Results:Compared with the control group, GLS, LSendo, LSmid and LSepi of the left ventricle in the TAVI preoperation group were decreased (all P<0.05), LSendo increased at 1 week after TAVI, and GLS, LSendo, LSmid, and LSepi increased at 3 months after TAVI (all P<0.05). In the TAVI preoperative, invasive aortic pressure was positively correlated with peripheral brachial artery systolic blood pressure, invasive left ventricular systolic pressure was positively correlated with non-invasive left ventricular systolic pressure ( r=0.658, 0.565; all P<0.01). Compared with the control group, the preoperative the GWE decreased and the GWW increased in the TAVI group (all P<0.05). Compared with the preoperation, the GWI and GCW decreased at 1 week after TAVI (all P<0.05). Compared with 1 week after TAVI, GWI, GCW, GWE increased and GWW decreased at 3 months after TAVI (all P<0.05). Conclusions:The application of 2D-STI and PSL can quantitatively evaluate the left ventricular myocardial systolic function before and after TAVI in AS patients, which can provide a more objective reference index for clinical evaluation of the efficacy of TAVI.

Objective:To assess the changes of left ventricular systolic function and global synchronization and myocardial work in patients with left bundle branch pacing (LBBP) by two-dimensional multi-layered speckle tracking imaging.Methods:Forty-two patients with Ⅱ degree Ⅱ type or Ⅲ degree atrioventricular block (AVB) in the Cardiovascular Hospital of Xiamen University from April to December 2019 were selected as pacing group, which were further divided into two groups according to different pacemaker modes: twenty patients with right ventricular septal pacing (RVSP), twenty-two patients with LBBP, and twenty patients with normal ECG and cardiac structure were enrolled as control group. Echocardiography of pacing group and control group was performed and analyzed. The left ventricular subendocardial longitudinal strain peak(LSendo), the middle layer myocardial longitudinal strain peak(LSmid), subepicardial longitudinal strain peak(LSepi), global myocardial longitudinal strain peak(GLS), peak strain dispersion (PSD), global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were acquired. The differences among the three groups were analyzed and the high difference indexes were screened by statistical modeling.Results:LSendo in three groups had no difference ( P>0.05). LSmid, LSepi, GLS in the control group, LBBP group and RVSP groups were decreased gradually ( P<0.05). GLS in LBBP group was higher than in RVSP group ( P<0.05). Compared with the control group, the increases of QRS and PSD in LBBP group were not statistically significant ( P>0.05), while the decreases of QRS and PSD in LBBP group were statistically significant compared with the RVSP group ( P<0.05). The values of GCW among three groups had no statistical significance ( P>0.05). Compared with the control group, the decrease of GWI in LBBP group was not statistically significant ( P>0.05), while the increase of GWW and the decrease of GWE were statistically significant ( P<0.05). Compared with the RVSP group, the increases of GWI and GWE and the decrease of GWW in LBBP group were statistically significant ( P<0.05). QRS, LSendo, GLS, LSmid, left ventricular apex rotation to basal rotation peak time(ApexBase period) were the indexes with significant difference among LBBP and RVSP groups and all index characteristics showed better in LBBP than RVSP group. Conclusions:Two-dimensional multi-layered speckle tracking imaging can be used to evaluate the effect of LBBP on left ventricular systolic function and global synchronization and myocardial work. LBBP longitudinal mechanical synchronization is better than right ventricular septal pacing by improving the peak global myocardial longitudinal strain and myocardial work after pacemaker.

Objective: To investigate the prenatal ultrasonographic features and prognosis of vasa previa, to explore the application value of sector scanning in the intracervical mouth by antenatal ultrasound, then to increase vasa previa detection rate. Methods: Prenatal ultrasound images, clinical characteristics and pregnancy outcome of 35 pregnant women with vasa previa confirmed by surgery and pathology were analyzed retrospectively, the diagnostic effectiveness of sector scanning in the intracervical mouth was evaluated. Results: Thirty-three of the 35 vasa previa cases were detected by sector scanning in the intracervical mouth, with a detection rate of 94.3% (33/35). Of the 35 cases, 20 cases (60.6%) were first contacted in second trimester and 13 cases (39.4%) were first contacted in third trimester. Two cases were missed or misdiagnosed, which were all first contact in third trimester. Among the 35 cases, 25 were velamentous placenta and 4 were battledore placenta. Twenty cases were low-lying placenta or marginal placenta previa. All 35 women underwent cesarean section. No neonatal mortality, 11 term infants, 20 premature infants of more than 34 weeks and 4 premature infants of less than 34 weeks. All placentas underwent pathological examination after delivery, 4 cases placentas underwent vascular casting, and it was found that 2 cases were vasa previa of umbilical artery branch and 2 cases were vasa previa of allantoic veins branch. Conclusions Vasa previa can be effectively detected by prenatal ultrasonography through sector scanning in the intracervical mouth. Second trimester is the best period to detect vasa previa. Pathomorphological examination on placenta after delivery and vascular casting are helpful to the understanding of vasa previa.

Objective To explore the value of the cavum vergae vanishing sign for prenatal ultrasound diagnosis of fetal agenesis of the corpus callosum ( ACC ) . Methods Fifty-one cases of ACC of 20 - 32 gestational weeks were confirmed by MRI or induced fetal autopsy . A random selection of 80 normal fetuses of 20 - 32 gestational weeks were chosed as control group . The displays of the cavum septum pellucidum ( CSP) and the cavum vergae( CV ) in the two groups were observed . Results There were 36 cases of complete agenesis of the corpus callosum ( CACC) and 15 cases of partial agenesis of the corpus callusom ( PACC) in ACC group . In 51 ACC cases ,43 cases were confirmed by prenatal MRI ,while 8 cases were confirmed by postnatal MRI . The comparison of display of CSP and CV between the ACC group and the health group was as follows : ① CSP vanishing rate in ACC group was 70 .6％ ( 36/51 ) ,meanwhile the disappearance rate of CSP in the health group was 0 ( 0/80 ) ,the difference between the two groups was statistically significant( χ2 = 77 .870 , P = 0 .000) . ② CV vanishing rate in ACC group was 96 .1％ (49/51) , meanwhile the disappearance rate of CV in the health group was 1 .2％ ( 1/80) ,the difference between the two groups was statistically significant ( χ2 = 118 .673 , P = 0 .000) . The correlation coefficient between the CV vanishing sign and the occurrence of ACC was 0 .952 ( P = 0 .000) ,while the correlation coefficient between the CSP vanishing sign and the occurrence of ACC was 0 .771 ( P = 0 .000) . There were significant differences in CSP disappearance rate and CV disappearance rate between ACC group and control group at different gestational weeks ( 20 - 24 weeks ,25 - 28 weeks and 29 - 32 weeks) ( all P < 0 .001) . Conclusions The cavum vergae vanishing sign ,as an important indirect sign of fetal agenesis of the corpus callosum ,can be obtained quickly from horizontal transverse section of the cavum septum pellucidum . During the middle pregnancy ,it could be an important prenatal ultrasound screening clue for fetal agenesis of the corpus callosum .