ObjectiveTo clarify the relationship between intestinal flora and intestinal motility in rats with slow transit constipation （STC） and qi stagnation syndrome by conducting a pseudo-sterile experiment and fecal microbiota transplantation （FMT） technology. MethodsTwenty-four Wistar rats were randomly divided into normal group （n=6）， STC with qi stagnation pattern group （n=6） and pseudo-sterile group （n=12）. In the STC group with qi stagnation pattern， 3 mg/kg of loperamide suspension by intragastric administration combined with tail clamping stimulation were performed to establish the rat model of STC with qi stagnation pattern. After successful modeling， fresh feces from the rats in the STC with qi stagnation pattern group and the normal group were collected to prepare 100 mg/ml of fecal bacterial suspension. In the pseudo-sterile group， the antibiotic cocktail method was used （a mixed antibiotic suspension containing bacitracin， streptomycin sulfate， and neomycin sulfate at 20 mg/ml each was administered intragastrically） to establish pseudo-sterile rats model. After successful modeling， the rats were randomly divided into normal fecal bacterial liquid group and STC with qi stagnation pattern fecal bacterial liquid group， with six rats in each group， and then were given 10 ml/kg of the prepared corresponding rat fecal bacterial suspension by gavage. Rats in STC with qi stagnation pattern group were given an equal volume of sterile water by gavage. All groups were administered once a day for 7 consecutive days. The small intestinal propulsion rate of the STC with qi stagnation pattern group， the normal fecal bacterial liquid group， and STC with qi stagnation pattern fecal bacterial liquid group were compared. ELISA method was used to detect serum 5-hydroxytryptamine （5-HT） levels. Immunohistochemistry was used to detect the positive expression levels of 5-hydroxytryptamine 3 receptor （5-HT3R） and 5-hydroxytryptamine 4 receptor （5-HT4R） in colon tissue. Western blot method was used to detect the protein expression levels of tryptophan hydroxylase 1 （TPH1）， tryptophan hydroxylase 2 （TPH2）， serotonin transporter （SERT）， and monoamine oxidase A （MAO-A） in colon tissue. ResultsCompared to those in the normal fecal bacterial liquid group， the small intestinal propulsion rate， serum 5-HT level， positive expression of 5-HT3R and 5-HT4R in colon tissue， and protein expression of TPH1， TPH2， SERT and MAO-A significantly decreased in the STC with qi stagnation pattern group and STC with qi stagnation pattern fecal bacterial liquid group （P＜0.05）. There was no statistically significant difference in the indicators between the STC with qi stagnation pattern group and STC with qi stagnation pattern fecal bacterial liquid group （P＞0.05）. ConclusionThe intestinal flora in STC rats with qi stagnation pattern can lead to a slowdown in intestinal transmission function， whose mechanism may be related to intestinal motility disorders affected by the synthesis， transport， metabolism and other pathways of 5-HT.

Objective:To investigate the efficacy and safety of different transcatheter arterial chemoembolization(TACE)-based regimens in patients with unresectable hepatocellular carcinoma(uHCC)and explore the optimal timing for combining TACE with tyrosine kinase inhibit-ors(TKIs)and immune checkpoint inhibitors(ICIs).Methods:A retrospective analysis was conducted on data from 555 patients with uHCC who underwent TACE-based treatment between April 2016 and December 2021 in Nanfang Hospital,Southern Medical University.The pa-tients were assigned into the following four groups according to different treatment regimens:TACE group(n=317),TACE combined with TKIs group(TACE+TKIs,n=66),TACE combined with ICIs group(TACE+ICIs,n=33),and TACE combined with TKIs+ICIs group(TACE+TKIs+ICIs,n=139).Subgroup analysis was performed within the TACE+TKIs+ICIs group,with patients being assigned into"pre-TACE"and"post-TACE"groups based on the timing of the combination therapy.Univariate and multivariate Cox regression analyses were conducted to identify pro-gnostic factors influencing overall survival(OS).Results:The TACE+TKIs+ICIs group showed the longest OS(21.9 months,95%confidence in-terval[CI]:17.2-26.6,P=0.030)and progression-free survival(PFS)(8.3 months,95%CI:7.3-9.3,P=0.004)compared to those in the other three groups.In the subgroup analysis,the"post-TACE"group had longer OS than the"pre-TACE"group(26.8 months vs.19.2 months,P = 0.011).The objective response rate(ORR)was 32.8%,41.1%,42.4%,and 52.5%(P=0.001)and the disease control rate(DCR)was 59.6%,71.2%,69.7%,and 82.7%(P<0.001)in the TACE,TACE+TKIs,TACE+ICIs,and TACE+TKIs+ICIs groups,respectively.The adverse events were similar to those reported in previous studies.Cox regression analysis revealed that tumor number,extrahepatic metastasis,and treatment regimen were independent factors influencing OS in patients(all P<0.05).Conclusions:TKIs or ICIs can improve OS and PFS in patients with uHCC receiving TACE,and the combination of TKIs+ICIs with TACE achieves better beneficial outcomes.The greatest OS was observed when the combination therapy TKIs+ICIs was initiated within 3 months after the first TACE procedure.

Liver cancer is the second-highest mortality cancer in China. It is highly occult, and there is no effective treatment so far. In recent years, stem cell transplantation, especially mesenchymal stem cell (MSCs) transplantation, has been widely used in the treatment of various diseases. Nevertheless, the industry has reached a consensus that malignant tumors are the forbidden area of this transplantation therapy. This is closely related to the two main characteristics of stem cells themselves, namely "self-renewal" and "pluripotency". The following is an overview of the reasons why stem cells, especially MSCs, have become taboo in tumor treatment and their potential application methods, so as to provide some references for further research on this therapy.

Objective To observe the characteristics of apathy in early Parkinson′s disease patients,analyze its relationship with other non?motor symptoms, and explore its impact on the quality of life.Methods Clinical data of 75 patients with Parkinson′s disease admitted to xingtai people′s hospital from August 2014 to August 2017 were selected.Unified Parkinson′s disease rating scale?III(UPDRS?III ), Modified apathy rating scale ( MAES ), Montgomy?asberg Depression rating scale ( MADRS ) and Simple mental state test ( MMSE) were used to evaluate patients′ motor symptoms, indifference, depression and cognitive function.The relationship between apathy and other non?motor symptoms was analyzed by Parkinson′s disease non?motor symptom evaluation scale.Parkinson′s disease questionnaire?39 ( PDQ?39) was used to evaluate the quality of life.The patients were divided into the affective indifference group and the non?affective indifference group according to whether the patients were accompanied by affective indifference.Results 21.3%( 16／75) of the patients were diagnosed with apathy.Emotional indifference group UPDRS score ?Ⅲ(23.98±9.46),not apathy group(14.74±6.27).There was significant difference between the two groups (P＜0.001).MMSE score of the indifferent group was ( 21.26±3.21),and that of the non?indifferent group was (26.57± 3.42).There was significant difference between the two groups ( P＝0.038).PDQ?39 score of the emotionally indifferent group was (65.20± 25.78),which was significantly higher than that of the non?emotionally indifferent group ( 34.86± 25.42).There was significant difference between the two groups (P＜0.001).In the comparison of Parkinson′s disease non?motor symptom evaluation scale,the fatigue symptom score of the emotionally indifferent group was (6.1±0.2) significantly higher than that of the non?indifferent group (2.3±0.7),and the difference was statistically significant (P＝0.006).The score of lack of interest was ( 4.8 ± 1.5) in the indifferent group and ( 1.3 ± 0.8) in the non?indifferent group.The difference between the two groups was statistically significant (P＝0.017).Conclusion Apathy has a high incidence in early Parkinson′s disease patients,often combined with fatigue and lack of interest symptoms.It has a serious impact on the quality of daily life in the future.

Objective To explore the effect of anti-retroviral therapy on interleukin(IL)-7/IL-7R in human immunodeficiency virus(HIV) infected patients in China.Methods Cases were divided into 2 groups:HIV-infected group (35 cases),and control group (30 cases).IL-7 in serum,IL-7R(CD127) expression in CD4 +T cells,and CD4 +T cells count were detected and compared between two groups before and after treatment for 1 year.Results IL-7 level in the serum of HIV infected group before treatment [(8.98 ±3.77) pg/ml] was significantly higher than that in control group [(3.84 ±0.86) pg/ml] (P ＜0.05).The counts of CD4+T cells [(202.65 ± 121.54)/μl],CD4 + CD127 + T cells [(60.25 ± 11.75) ％],and CD8 + CD127 + T cells [(46.27 ± 12.10)％] in HIV-infected group were significantly lower than those in control group [(766.99 ± 103.21)/L,(76.89 ± 20.01) ％,(81.27 ± 12.35)％] (P ＜0.05).After anti-retroviral therapy (ART),IL-7 level in the serum of HIV-infected group[(5.55 ± 1.35) pg/ml]was decreased,and CD4+T cells [(450.58 ± 15)/μl],CD4 + CD127 +T cells [(69.82 ± 15.24)％],and [CD8 + CD127 + T(59.23± 14.73) ％] cells was increased in HIV-infected group,with a significant difference between two groups (P ＜0.05).Conclusions ART could improve the IL-7 level in the serum and IL-7R(CD127)expression in CD4 +T cells of HIV-infected patients.However,they still cannot become normal level.

Objective To evaluate the application of CT myelography (CTM) in detecting the site of spontaneous cerebrospinal fluid (CSF) leaks and analyze it's imaging features.Methods Six patients (3 women and 3 men) with spontaneous intracranial hypotension (SIH) were included, who met the criteria of the International Headache Classification (2nd edition, 2004). Five patients subsequently underwent whole spine MRI and all 6 patients underwent CTM. Autologous blood mixed with omnipaque (300 mg/ml) was injected followed by selective puncture at the leak site indicated by CTM. Results MRI was failed to find leak site in the 5 patients, whereas CTM successfully found leak sites in all 6 patients. There were 1 to 7 leak sites respectively with an average of 4.2 sites (totally 25 points). Leak sites at cervical (12 sites) and thoracic (12 sites) were more frequent than at lumbar (1 site). CTM was featured by linear leakage of the contrast medium along the spinal nerve roots, paraspinal collections of hyper-density contrast medium and beak-like enlargement of the nerve sleeves. All patients responded well to the treatment, with complete resolution of symptoms. Conclusion CTM has been shown to be a study of choice to accurately define the location and extent of a CSF leak.

Objective To detect the changes in the expression of discoidin domain receptor 2(DDR2)and matrix metalloproteinase (MMP)-13 in different stages of cartilage and synovium damage of osteoarthritis rats.The relation between DDR2 and the degree of cartilage damage was explored.Methods Modified papain knee joint injection approach was adopted to establish animal model of OA.The expression and distribution of protein of DDR2 and MMP-13 were checked in articular cartilage and synovium at different stages of OA.Results The expressions of DDR2 in articular cartilage and synovium of experimental groups were different from those of the normal group (P＜0.01).They were higher in cartilage than those in the corresponding synovium.The expressions of MMP-13 demonstrated the same characteristics with those of DDR2,r=0.93(P＜0.01).Conclusions The important role of DDR2-MMP-13 in cartilage damage has been proven in the pathogenic process of OA.The upregulated expressions of DDR2 in articular cartilage and synovium have a detrimental effect on cartilage degeneration.

Objective To study the regulatory effect of triptolide(TP)on the angiogenesis of coll-agen-induced arthritis(CIA) rats.The effect of TP on arthritis is also explored.Methods After the model of CIA was established,the articular volume was measured and the synovium was examined with regular HE stainand the inflammation and pathological changes were evaluated.In addition,the vascular endothelial growth factor (VEGF),basic fibroblast growth factor (bFGF)and endostatin protein expressions in synovium and serum were tested.The micro-vessel density (MVD) of synovium was also measured by caulating CD34 level.Results The expressions of VEGF,bFGF and MVD in CIA rats'synovium and serum were evidently higher than the control group(X2=65.3,31.6,q=9.2,P＜O.01,respectively),while the expression of endostatin showed no statistical difference with controls (X2=0.8,P＞0.05).After treated with TP,the expressions of VEGF,bFGFand MVD decreased markedly(X2=19.7,6.0,q=6.5,P＜O.01,respectively),but the pmtein expression of endostatin significantly increased (X2=3.9,P＜O.05).However,only the expression of endostatin increased significantly after treated with MTX (X2=17.9,P＜0.01).Conclusion Imbalance in growth factors prnduction may play an important role in the process of arthritis development.Re-establishing the balance of growth factors maybe one of the mechanisms of TP in the treatment of arthritis.

AIM: To determine whether triptolide induce apoptosis of synovial cells in collagen - induced arthritis(CIA) in rats. METHODS: The male Wistar rats were used to make CIA models by immunized with Bovine collagen Ⅱ ( BC Ⅱ )in Freund's complete adjuvant (FCA). A total of 20 CIA rats were randomly divided into 2 groups, triptolide group (10 rats) and CIA control group (10 rats). Triptolide group were administered with triptolide at 40 μg/kg body weight intramuscularly every three days. CIA control group andanother 10 age - matched normal rats were given normal saline instead. The rats were sacrificed on the 31st day after the triptolide administration. The pieces of synovium of the rat knee joints were harvested. The synovium was examined by HE staining and electron microscope. The apoptosis was tested by TUNEL and flow cytometer. RESULTS: The earlier phase of apoptotic synoviocytes were observed under the electron microscope. The flow cytometry showed that the percentage of the apoptotic cells was (3.98 ± 1.16)% in the triptolide group, (1.83 ± 0.82)% in the CIA control group, and (0.87 ±0.24)% in the normal group (P＜0.01: triptolide vs control group). While the percentage of the cells in DNA synthesis phase was (3.3± 1.2)% in the triptolide goup, (8.0± 1.4)% in the CIA control group, and (3.4 ± 0.7)% in the normal group.There is significantly different in the apoptosis changes between the triptolide group and the CIA control group ( P ＜ 0.01: triptolide vs CIA control group). The TUNEL labeling demonstrated that the percentage of the apoptotic cells was (4.5 ± 1.0)% in the triptolide group, (2.2 ± 1.0) % in the CIA control group, and ( 1.0 ± 0.4) % in the normal group. The difference of apoptotic rate between the triptolide group and the CIA control group is significant ( P ＜ 0.01). CONCLUSION: This study demonstrates that triptolide can induce apoptosis in CIA rats, which may be one of the mechanisms that triptolide treats the rheumatoid arthritis.

The relationship between tumour necrosis factor-α (TNF-α) gene polymorphism and inhibitory effects of triptolide on TNF-α production from peripheral blood mononuclear cells (PBMC)of healthy humans was investigated. Genomic DNA from 41 healthy people was typed for TNF-α-308 polymorphism by allele-specific polymorphism chain reaction (AS-PCR). The TNF-α concentration in the supernatant was measured by ELISA. The results showed that the production of TNF-α from TNF-α -308 non-G/G genotype PBMC was higher than that from TNF-α-308 G/G genotype PBMC after stimulated by LPS. Triptolide could lower the production of TNF-α from G/G genotype PBMC, but had no effect on the level of TNF-α from non-G/G genotype PBMC. It was concluded that TNF-α gene polymorphism was related to the TNF-α production from triptolide-inhibited PBMC culture in healthy humans.