Objective : To investigate the antidepressant effects and the underlying mechanisms of tetrahydrocurcumin(THC) and its nanoparticle formulation(THCN). Methods : Forty-six male ICR mice were randomly divided into Con group, LPS group, THC group, THCN group and SER group. A mouse depression model was established by intraperitoneal administration of LPS. The anxiety and depression-like behaviors of mice were evaluated by open field test(OFT) and forced swimming test(FST). Myelin staining was applied to assess the extent of demyelination in the prefrontal cortex of the mice. The prefrontal cortex and hippocampus were further examined for the expression levels of glial fibrillary acidic protein(GFAP) and Toll-like receptor 4(TLR4) through quantitative immunofluorescence assays. Results : Compared with the Con group, the LPS group showed increased anxiety-like and depressive-like behaviors in both the long-term and short-term experiments(P<0.05); the degree of demyelination increased in the LPS group of the long-term experiment(P<0.01); the expression of GFAP was reduced in the LPS group of the short-term experiment(P<0.01), while the expression of TLR4 increased(P<0.05); the expression of TLR4 decreased in the THC group(P<0.01); the expression of GFAP in the prefrontal cortex of the THCN group was reduced(P<0.01), while the expression of TLR4 increased(P<0.05). Compared with the LPS group, the THC group showed reduced depressive-like behaviors in the long-term experiment(P<0.05), while the anxiety-like and depressive-like behaviors of the THCN group and the SER group were reduced(P<0.05), and the anxiety-like and depressive-like behaviors of the THC group and the THCN group were reduced in the short-term experiment(P<0.05); the degree of demyelination was reduced in the THC group, THCN group and SER group in the long-term experiment(P<0.05); the expression of GFAP increased in the THC group of the short-term experiment(P<0.05), while the expression of TLR4 was reduced(P<0.05), and the expression of GFAP increased in the THCN group(P<0.05). Compared with the THC group, the THCN group and the SER group showed reduced anxiety-like behaviors in the long-term experiment(P<0.05); the expression of GFAP in the prefrontal cortex of the THCN group was reduced in the short-term experiment(P<0.05), while the expression of TLR4 in the hippocampal DG area increased in the short-term experiment(P<0.01). Conclusion Tetrahydrocurcumin and its nanoparticle formulation both exert significant ameliorative effects on depression-like behaviors and demyelination in mice induced by lipopolysaccharide. The antidepressant mechanism of THC appears to be mediated through the down-regulation of TLR4 and the up-regulation of GFAP. The mechanism underlying the antidepressant action of THCN seems predominantly focused on the enhancement of GFAP expression.

OBJECTIVE To explore the effect of Huangqin decoction on improving peritubular fat inflammatory microenvironment and protecting vascular endothelial function in obese hypertensive rats by regulating the NEK7-NLRP3/IL-1β inflammatory axis.METHODS Fifty 4-week-old male Wistar rats were selected,10 of which were randomly selected as the control group,and the oth-er 40 were fed a high-salt and high-fat diet to establish an obese hypertension model.The rats with successful modeling(20 rats)were randomly divided into the model group,normal-dose Huangqin decoction group,high-dose Huangqin decoction group,and IL-1β in-hibitor group,with 5 rats in each group.From the 12th week,the normal-dose group was gavaged with Huangqin decoction 2.835 g·kg-1,the high-dose group was gavaged with Huangqin decoction 5.67 g·kg-1,and the IL-1β inhibitor group was intraper-itoneally injected with 1.5 mg·kg-1 AS101,3 times a week,for 8 weeks.The rats were weighed and blood was collected 12 h after the last administration,and the thoracic aorta and perivascular fat tissue were isolated.Serum inflammatory factors were detected,patho-logical changes were observed,eNOS expression was detected by immunofluorescence,and NEK7,NLRP3,Caspase-1,ASC,and IL-1β expression levels were detected by Western blot and qPCR.RESULTS The rats in the model group had a significant increase in body weight,an increase in the area of peritubular fat lipid droplets,and severe endothelial injury;systolic blood pressure,diastolic blood pressure,serum IL-1β,IL-6,and TNF-α were significantly elevated in the model group,and the expression of eNOS was sig-nificantly reduced,and the expression levels of NEK7,NLRP3,Caspase-1,ASC,and IL-1β proteins and mRNAs were significantly elevated.Compared with the model group,rats in the Huangqin decoction and IL-1β inhibitor groups had lower body weights,reduced endothelial damage,lower systolic and diastolic blood pressures,lower serum IL-1β,IL-6,and TNF-α,and higher eNOS expression.NEK7,NLRP3,Caspase-1,ASC and IL-1β protein expression was significantly reduced in the high dose group of Huan-gqin decoction and the IL-1β inhibitor group.In addition,Huangqin decoction protected the endothelial function of obese hypertensive vessels in a dose-dependent manner,with the effect being more pronounced in the high-dose group.CONCLUSION Huangqin de-coction can improve the inflammatory microenvironment of perivascular fat and protect the vascular endothelial function in obese hyper-tension by regulating the NEK7-NLRP3/IL-1β inflammatory axis.

Objective To study the mechanism of Wenyang Jieyu Granules via cAMP-MAPK signaling pathway in hippocampus of chronic unpredictable mild stress(CUMS)model rats.Methods CUMS was used to establish depression model in rats.The depression state of rats was reflected by sucrose preference test,forced swimming test and open field test.The expressions of cAMP,phosphorylated extracellular signal-regulated kinase(p-ERK)and Raf protein kinase-1(Raf-1)in rat hippocampus were detected by enzyme-linked immunoassay(ELISA).Western blot was used to detect the expressions of cyclic adenosine phosphate response element binding protein(CREB),phosphorylated cyclic adenosine phosphate response element binding protein(p-CREB),extracellular signal-regulated kinase(ERK)and Mitogen-activatsion ofed Extracellular signal-regulated Kinas(MEK)in rat hippocampus.The mRNA expres cAMP,CREB,cyclic adenosine phosphate dependent protein kinase A(PKA),brain-derived neurotrophic factor(BDNF),and rat sarcoma(Ras)in rat hippocampus was detected by RT-PCR.The expression of caspase-3(caspase-3)in rath hippocampus was observed by immunohistochemistry.Results Compared with the model group,the body weight,sucrose preference rate and open field distance of model rats were increased in the positive control group and Wenyang Jieyu Granules group(P<0.05,P<0.01),and reduce the immobility time of forced swimming(P<0.05,P<0.01).It also increased the levels of cAMP,p-ERK,Raf-1,CREB,p-CREB,p-CREB/CREB,ERK and MEK in hippocampus of CUMS model rats(P<0.05,P<0.01).At the same time,the expression of cAMP,CREB,PKA,BDNF and Ras mRNA in the hippocampus of model rats were significantly improved(P<0.05,P<0.01),and he expression of caspase-3 in the hippocampus was reduced(P<0.05).Conclusion Wenyang Jieyu granules may exert antidepressant effect on model rats through cAMP and MAPK signaling pathways.

OBJECTIVE To investigate the effects of Wenyang jieyu decoction on phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and neurotransmitters in rats with kidney-yang deficiency depression. METHODS The SD rats were divided into blank group， model group， fluoxetine group （positive control of western medicine， 4.17 mg/kg）， Xiaoyao powder group （positive control of TCM， 1.88 g/kg） and Wenyang jieyu decoction low-dose， medium-dose and high-dose groups （1.25， 2.50， 5.00 g/kg）， with 15 rats in each group. Except for blank group， the other groups were treated with corticosterone 20 mg/kg subcutaneously to induce kidney-yang deficiency depressed model， meanwhile the mice were given relevant medicine intragastrically， once a day， for 28 consecutive days. The general conditions of rats were observed. The sucrose preference rate and the static time of forced swimming were detected， and organ indexes of rats were calculated. The levels/contents of neurotransmitters in serum were detected， the expressions of PI3K/Akt pathway-related proteins in hippocampus were detected， and the number of dendritic spines was determined. RESULTS Compared with blank group， model group suffered from the symptoms such as hair loss， fear of cold， curling up； sucrose preference rate， indexes of adrenal gland， thymus gland and spleen，serum levels of cyclic adenosine phosphate （cAMP）， brain-derived neurotrophic factor and gamma-aminobutyric acid， the ratio of cAMP to cyclic guanosine monophosphate， the contents of norepinephrine， dopamine and 5-hydroxy-tryptamine， the expressions of PI3K， Akt， mammalian target of rapamycin， and the number of dendritic spines in the hippocampus were significantly decreased （P＜0.01）. The time of immobility， level of glutamic acid and protein expression of glycogen synthetase kinase-3β were prolonged and increased （P＜0.01）. Compared with model group， depression symptoms of rats in each administration group were improved， and the above indexes were mostly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Wenyang jieyu decoction can improve depression-like behavior and the deficiency of kidney-yang， regulate the secretion of neurotransmitters， and activate PI3K/Akt signaling pathway， thus playing a role in protecting hippocampal neurons.

Objective:To investigate the value of multi-slice spiral CT (MSCT) combined with three myocardial markers in the diagnosis of acute chest pain etiology.Methods:A retrospective study was conducted on 120 patients with acute chest pain admitted to the Affiliated Hospital of Jining Medical University from January 2020 to December 2020. All patients underwent MSCT imaging examination upon admission, and serum creatine kinase isoenzyme MB (CK-MB), troponin I (cTnI), and myoglobin (MYO) levels were also tested. The final clinical diagnosis was used as the judgment standard to draw a 2×2 four-square table, and calculate the value of MSCT, CK-MB, cTnI, and MYO in the diagnosis of acute chest pain etiology.Resultsl:Among the 120 acute chest pain patients included, 75 were diagnosed with acute coronary syndrome (62.50%), 16 with aortic dissection (13.33%), and 29 with pulmonary embolism (24.17%). The coincidence rate of MSCT diagnosis of coronary heart disease was 86.67%(65/75), the diagnosis of aortic dissection coincidence rate was 12/16, and the diagnosis of pulmonary embolism coincidence rate was 75.86%(22/29). The serum CK-MB, cTnI, and MYO levels in the coronary heart disease group were significantly higher than those in the aortic dissection group and pulmonary embolism group, and the differences were statistically significant (all P<0.05). There was no significant difference in serum CK-MB, cTnI, and MYO levels between the aortic dissection group and pulmonary embolism group (all P>0.05). The sensitivity of CK-MB, cTnI, and MYO in the differential diagnosis of acute chest pain patients with coronary heart disease and non-coronary heart disease were 93.33%, 85.33%, and 89.33%, respectively, and the specificity were 73.33%, 80.00%, and 77.78%, respectively. The areas under the receiver operating characteristic (ROC) curve were 0.833, 0.826, and 0.836, respectively. Conclusions:MSCT can better identify coronary heart disease, aortic dissection, and pulmonary embolism in patients with acute chest pain, while the three myocardial markers can better distinguish patients with coronary heart disease and non-coronary heart disease. Therefore, MSCT combined with myocardial markers should be used for the diagnosis of acute chest pain patients in clinical practice to facilitate early clinical diagnosis.

Objective:To evaluate the acute effects of different foot-strike patterns of running on knee cartilage in amateur marathon runners using the T 2* mapping technique. Methods:From November 2021 to February 2022, 29 amateur marathon runners were recruited in Hangzhou. The gait analysis was performed to determine their landing patterns, then the runners were divided into the fore-foot strike (FFS) group (11 cases) and the rear-foot strike (RFS) group (18 cases). The MRI of the knee joint of the dominant leg was performed before and 30 min after running, and the volume, thickness, and T 2* value of each division of knee cartilage were measured. Independent samples t-tests were used to compare the differences in baseline data before running between the groups, and paired samples t-tests were used to compare the differences before and after running within the groups. Results:The difference in knee cartilage volume and thickness between the FFS and RFS groups before running was not statistically significant ( P>0.05), and the T 2* value of the femur medial posterior in the RFS group was higher than that of the FFS group ( t=-2.47, P=0.020). Compared with pre-running, cartilage thickness of the tibia lateral posterior decreased in the FFS group after running ( t=-2.96, P=0.016), and cartilage thickness of the tibia lateral posterior and patella lateral central decreased in the RFS group ( t=-3.25, -3.02, P=0.004, 0.007). Cartilage volume of the tibia lateral posterior decreased in the FFS group after running ( t=-2.58, P=0.030), and the cartilage volume of the patella lateral central decreased in the RFS group ( t=-2.74, P=0.013). The differences in T 2* values of cartilage in each region before and after running were not statistically significant in the FFS group ( P>0.05), whereas in the RFS group, the cartilage T 2* values in the femur medial posterior, femoral trochanter central, femoral trochanter lateral, femur lateral central, tibia lateral anterior, tibia medial posterior, tibia medial central, and tibia medial anterior decreased ( P<0.05). Conclusions:After running, FFS showed changes in morphology and biochemical composition only in some subregions of tibial cartilage, whereas most of the femoral cartilage, patellar cartilage, and tibial cartilage regions were altered by RFS. The RFS pattern introduces greater acute changes in cartilage in the knee joint.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective:To analyze the diagnostic value of cell-free plasma metagenomic next-generation sequencing (mNGS) pathogen identification for severe aplastic anemia (SAA) bloodstream infection.Methods:From February 2021 to February 2022, mNGS and conventional detection methods (blood culture, etc.) were used to detect 33 samples from 29 consecutive AA patients admitted to the Anemia Diagnosis and Treatment Center of the Hematology Hospital of the Chinese Academy of Medical Sciences to assess the diagnostic consistency of mNGS and conventional detection, as well as the impact on clinical treatment benefits and clinical accuracy.Results:①Among the 33 samples evaluated by mNGS and conventional detection methods, 25 cases (75.76%) carried potential pathogenic microorganisms. A total of 72 pathogenic microorganisms were identified from all cases, of which 65 (90.28%) were detected only by mNGS. ②All 33 cases were evaluated for diagnostic consistency, of which 2 cases (6.06%) were Composite, 18 cases (54.55%) were mNGS only, 2 cases (6.06%) were Conventional method only, 1 case (3.03%) was both common compliances (mNGS/Conventional testing) , and 10 cases (30.3%) were completely non-conforming (None) . ③All 33 cases were evaluated for clinical treatment benefit. Among them, 8 cases (24.24%) received Initiation of targeted treatment, 1 case (3.03%) received Treatment de-escalation, 13 cases (39.39%) received Confirmation, and the remaining 11 cases (33.33%) received No clinical benefit. ④ The sensitivity of 80.77%, specificity of 70.00%, positive predictive value of 63.64%, negative predictive value of 84.85%, positive likelihood ratio of 2.692, and negative likelihood ratio of 0.275 distinguished mNGS from conventional detection methods (21/12 vs 5/28, P<0.001) . Conclusion:mNGS can not only contribute to accurately diagnosing bloodstream infection in patients with aplastic anemia, but can also help to guide accurate anti-infection treatment, and the clinical accuracy is high.

Objective:To retrospectively analyze the prognosis and related risk factors of lymph node metastasis in early-stage (Ⅰ B-Ⅱ A) cervical cancer patients with postoperative positive lymph nodes who were treated with intensity modulated radiotherapy (IMRT). Methods:A retrospective analysis was conducted for 292 early-stage cervical cancer patients with postoperative high and/or moderate risk factors who were treated with pelvic-abdominal IMRT with/without concurrent chemotherapy in Ningxia Medical University General Hospital from January 2016 to December 2018. These patients included 239 with negative pelvic lymph nodes and 53 with positive lymph nodes, who were incorporated into the negative group and the positive group, respectively. Multivariate and univariate analyses of the risk factors of lymph node metastasis and prognosis were performed for both groups.Results:The univariate and multivariate analyses showed that the lesion ≥4 cm, deep interstitial invasion, and the number of risk factors were independent factors influencing pelvic lymph node metastasis ( χ2 = 7.11, 9.05, 90.08, P < 0.05). There was no statistically significant difference in the 3- and 5-year OS ( P>0.05) between both groups. The 3-year disease-free survival (DFS) and 5-year DFS of the negative group were 87.6% and 84.5%, respectively, and those of the positive group were 72.5% and 69.3%, respectively ( χ2=8.59, P=0.003). Regarding failure modes, distant metastasis mainly occurred in the positive group, while local recurrence was dominant in the negative group ( χ2=9.40, P<0.05). The univariate analysis of the DFS in 53 patients with postoperative positive lymph nodes showed that deep interstitial invasion affected DFS, with statistically significant differences ( χ2 = 7.25, P < 0.05). The result of the multivariate analysis showed that the lesion size >4 cm, positive residual, and deep interstitial invasion significantly influenced the DFS ( χ2 = 4.37, 4.69, 4.39, P < 0.05). Conclusions:The lesion size, deep interstitial invasion, and risk factor number were independent factors influencing lymph node metastasis, and the DFS after radiotherapy of patients with pelvic lymph node metastasis was significantly lower than the patients with negative lymph nodes. The main recurrence type of patients with lymph node metastasis was distant metastasis. Moreover, the deep interstitial invasion was independent factor affecting the DFS of early-stage cervical cancer patients with postoperative positive lymph nodes.

Objective:To retrospectively analyze the differences of survival, recurrence, acute side effects and prognostic factors between early stage (stage ⅠB-ⅡA) cervical cancer patients with intermediate risk factors receiving postoperative concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone.Methods:Clinical data of 211 patients with intermediate risk factors after early stage cervical cancer surgery admitted to Department of Radiation Oncology of General Hospital of Ningxia Medical University from January 2016 to December 2018, were retrospectively analyzed. Among them, 91 cases were assigned in the RT group and 120 cases in CCRT group. The 3- and 5-year overall survival (OS), progression-free survival (PFS), recurrence and acute side effects were compared between two groups by Chi-square test. Univariate analysis of OS and PFS was performed by Kaplan-Meier method and log-rank test was performed. Multivariate prognostic analysis was conducted by using Cox model. Results:The 3- and 5-year OS of 211 patients were 95.0% and 93.8%, respectively. The 3- and 5-year PFS were 86.8% and 83.2%, respectively. The OS of CCRT and RT group were 93.9%, 96.5% (3-year), 91.8%, 96.5% (5-year) respectively ( χ2=1.763, P=0.184), and the PFS were 84.4%, 89.9% (3-year), 79.3%, 88.3% (5-year) ( χ2=2.619 ,P=0.106), with no difference between the two groups. The total recurrence rate was 15.64%, and there was no significant difference in the recurrence rate and recurrence area between two groups ( χ2=2.623 ,P=0.105; χ2=6.745 ,P=0.080). Locoregional recurrence and lung metastasis were the main patterns of failure. Multivariate prognostic analysis showed that pathological type might significantly affect the OS ( χ2=3.849, P=0.05), and depth of invasion significantly affected the PFS ( χ2=4.095, P=0.043). The incidence of acute gastrointestinal side effect and bone marrow suppression in the CCRT group was significantly higher than that in the RT group ( χ2=56.425, 27.833; both P<0.001). Conclusions:Patients with intermediate risk factors after early cervical cancer surgery obtain high efficacy after radiotherapy. The main patterns of failure are locoregional recurrence and lung metastasis. The pathological type may be an independent prognostic factor of OS and the depth of invasion is an independent prognostic factor of PFS. Compared with RT, CCRT increases the risk of acute gastrointestinal side effects and myelosuppression, which can be tolerated. There is no significant difference in the clinical efficacy between RT and CCRT, which remains to be validated by large sample size studies.