Objective:To explore the mechanism of Huangqi Jiedu Decoction (HQJD) in the treatment of breast cancer with the syndrome of Zheng deficiency and toxic incandescence by network pharmacology and molecular docking technology.Methods:The main active ingredients and targets of HQJD were screened through the traditional Chinese medicine (TCM) systematic pharmacology database and analysis platform. The relevant targets of breast cancer with the syndrome of Zheng-deficiency, toxic-incandescence were obtained using OMIM, GeneGards and Drugbank databases, and the relevant targets of HQJD for the treatment of breast cancer with the syndrome of Zheng-deficiency and toxic incandescence were obtained by intersection; The Cytoscape 3.9.1 software was used to build the protein protein interaction (PPI) network and the " drug active component target disease" network on the basis of String 11.0 database, and the core active components and core targets of HQJD in treating breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence were inferred according to the topological parameters. gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on core targets using R language; and molecular docking verification on the main active ingredients and core targets were conducted.Results:230 effective targets of active ingredients of HQJD were screened, and 15 467 active ingredients of breast cancer with syndrome of Zheng-deficiency/toxic-incandescence were obtained; 217 intersection targets; GO function enrichment analysis showed that the treatment of HQJD for breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence mainly involved oxidative stress and cytochemical stress; The enrichment analysis of KEGG pathway showed that HQJD treatment of breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence was mainly related to phosphatidylinositol 3-protein kinase B (PI3K-Akt), interleukin-17 (IL-17) and other signal pathways. The molecular docking results showed that the main active ingredients such as β-sitosterol, stigmasterol, luteolin had good binding ability with core targets.Conclusions:HQJD has the characteristics of multi-component, multi target and multi pathway in the treatment of breast cancer with syndrome of Zheng-deficiency and toxic-incandescence, and its main mechanism may be related to PI3K-Akt, IL-17, P53 and other signal pathways.

Objective:To explore the pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective.Methods:Thirty male C57BL/6 mice were randomly divided into control group and flunarizine group ( n=15). Mice in the control group were given 0.1 mL 50% polyethylene glycol 400+50% saline by gavage once/d for 2 weeks, while mice in the flunarizine group were given 6 mg/mL flunarizine+50% polyethylene glycol 400+50% saline by gavage at a daily dose of 30 mg/kg for 2 weeks. Body mass was recorded 1, 3, 5, 7, 10 and 14 d after drug administration, and motor function was assessed by rotarod test 14 d after drug administration; 16s RNA sequencing was performed in the feces to observe the intestinal flora; intestinal transit function was detected by Evans blue by gavage; and then, the mice were sacrificed and homogenate or frozen sections (brain and intestinal tissues) were prepared; dopamine-ergic neuron expression was detected by Western blotting; RT-qPCR was applied to detect the expressions of inflammatory factors in the substantia nigra, and immunofluorescent staining was used to detect the expressions of ZO-1 and Claudin-5 in the intestinal epithelial tissues. Results:Compared with the control group, the flunarizine group had lower body mass ratio 1, 3, 5, 7, 10 and 14 d after drug administration (ratio to body mass before drug administration). Compared with the control group, the flunarizine group had significantly shortened residence time in rod rotating and lower rotational speed when falling ( P<0.05). Compared with the control group, the flunarizine group had decreased tyrosine hydroxylase protein in the substantia nigra without significant difference ( P>0.05). Compared with the control group, the flunarizine group had significantly increased interleukin-6 and tumor necrosis factor-α in the substantia nigra (1.00±0.00 vs. 2.79±0.83; 1.00±0.00 vs. 3.39±1.37), significantly lower intestinal Evans blue propulsion rate (80.67%±4.51% vs. 50.67%±6.03%), and statistically decreased ZO-1 and Claudin-5 expressions in the colonic epithelial tissues (27.01±1.41 vs. 16.32±2.83; 37.00±2.80 vs. 24.52±2.12, P<0.05). Totally, 576 microorganisms were noted in both control group and flunarizine group, 744 in the control group alone, and 634 in the flunarizine group alone. The intestinal flora β diversity indices in the 2 groups were significantly different based on weighted Unifrac-principle coordinates analysis (PCoA, PCoA1: 39.88%; PCoA2: 30.69%). Compared with the control group, the microbial colony structure of mice in flunarizine group was dominated by phylum thick-walled bacteria and phylum warty microbacteria, and by families Muribaculaceae, Lachnospiraceae and Akkermansiaceae. Compared with the control group, the flunarizine group had significantly decreased relative abundance of Ackermannia spp. and Lactobacillus spp. in the intestinal flora ( P<0.05). Conclusion:Flunarizine may contribute to the pathogenesis of DIP by causing structural disturbances in the intestinal flora and inducing neuroinflammation based on the gut-brain axis.

Objective To develop and validate a fatigue risk nomogram model in Chronic Obstructive Pulmonary Disease(COPD)patients.Methods A prospective study design was adopted,and 430 COPD patients recruited from a tertiary A hospital in Huzhou City from January to December 2022 were conveniently selected for model construction,and 129 patients were recruited from the same hospital from January to June 2023 for external validation of the model.The general information questionnaire,Pittsburgh Sleep Quality Index,2-item Generalized Anxiety Disorder Scale,2-item Patient Health Questionnaire,modified British Medical Research Council Dyspnea Index,International Physical Activity Questionnaire,and Fatigue Severity Scale were used for questionnaire survey.The risk prediction model and nomograms model were constructed using Logistic regression analysis and R 4.3.2 software,and the area under the receiver operating characteristic(ROC)curve was used to test the prediction effect of the model.Results Univariate and binary logistic regression analysis results showed that age(OR=1.095),gender(OR=2.077),dyspnea(OR=3.309),sleep quality(OR=1.979),anemia(OR=3.289),the number of acute exacerbation(OR=2.991)were independent influencing factors for fatigue in COPD patients.The internal evaluation and external validation results of the model showed that the areas under the curve are 0.912 and 0.844 respectively,and the Hosmer-Lemeshow goodness of fit test P values were 0.806 and 0.526 respectively.The average absolute errors were 0.013 and 0.019 respectively.Conclusion The COPD fatigue risk prediction model constructed in this study has good prediction effect.The visual nomogram is intuitive,convenient and easy to operate.It can provide a tool for early screening of fatigue in COPD patients.

Objectives:To investigate the intravascular ultrasound(IVUS)evaluated efficacy of the"L-sandwich"technique in the percutaneous coronary intervention treatment of true bifurcation lesions of coronary artery. Methods:Ninety-nine patients with true bifurcation lesions(medina type 1.1.1)of the coronary arteries were divided into the L-sandwich group(n=38),the double-stent group(n=32),and the main vessel(MV)single-stent with side branch(SB)drug-coated balloon(DCB)only group(n=29).The primary study endpoint was the loss of late lumen area(LLAL)in the MV,SB ostium and SB shaft at 12 months,and the secondary endpoints were minimum lumen area(MLA)at each site and major adverse cardiac events(MACE)at 12 months.As this is a proof-of-concept study,statistical analyses were performed in the as-treated(AT)analysis set. Results:At 12-month follow-up,there was no statistically significant difference in the MV LLAL among patients in the"L-sandwich"technique group,the double stent technique group,and the MV DES with SB DCB technique group([0.12±0.42]mm2 vs.[0.07±0.38]mm2 vs.[-0.01±0.31]mm2,P=0.419).Similarly,there was no statistically significant difference in the LLAL at the SB shaft([-0.11±0.45]mm2 vs.[-0.10±0.28]mm2 vs.[0.24±1.04]mm2,P=0.078],with the maximum LLAL observed in the double stent technique group and the minimum in the"L-sandwich"technique group([-0.48±0.78]mm2 vs.[0.45±0.64]mm2 vs.[0.14±1.37]mm2,P<0.001).The MV MLA was similar among the three groups([8.39±1.65]mm2 vs.[8.28±0.98]mm2 vs.[8.02±1.37]mm2,P=0.565),while the maximum MLA at the SB ostium was observed in the double stent technique group and the minimum in the MV DES with SB DCB group([5.08±0.74]mm2 vs.[5.63±0.80]mm2 vs.[3.57±1.35]mm2,P<0.001).In terms of MLA at the SB shaft,the"L-sandwich"technique group was similar to the double stent technique group,while the MV DES with SB DCB group exhibited the minimum MLA([5.94±0.72]mm2 vs.[5.86±0.59]mm2 vs.[3.74±1.07]mm2,P<0.001).Two patients in the double stent technique group underwent target vessel revascularization,there was no MACE in the other two groups(P=0.118). Conclusions:The"L-sandwich"technique is safe and feasible for the treatment of coronary bifurcation lesions.Compared with double-stent group,the SB ostium has a smaller LLAL at the time of review,and there is no significant difference in the MLA of each site,and the operation steps are significantly simplified.Use of the"L-sandwich"technique is associated with a better branching benefit compared with MV single-stent group.The"L-sandwich"technique could be used as a remedial procedure for severe entrapment in the setting of branching with DCB alone.

Background/Aims: Disrupted bile acid regulation and accumulation in the liver can contribute to progressive liver damage and fibrosis. However, the effects of bile acids on the activation of hepatic stellate cells (HSCs) remain unclear. This study investigated the effects of bile acids on HSC activation during liver fibrosis, and examined the underlying mechanisms. Methods: The immortalized HSCs, LX-2 and JS-1cells were used for the in vitro study. in vitro, the adeno-associated viruses adeno-associated virus-sh-S1PR2 and JTE-013 were used to pharmacologically inhibit the activity of S1PR2 in a murine model of fibrosis induced by a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Histological and biochemical analyses were performed to study the involvement of S1PR2 in the regulation of fibrogenic factors as well as the activation properties of HSCs. Results: S1PR2 was the predominant S1PR expressed in HSCs and was upregulated during taurocholic acid (TCA) stimulation and in cholestatic liver fibrosis mice. TCA-induced HSC proliferation, migration and contraction and extracellular matrix protein secretion were inhibited by JTE-013 and a specific shRNA targeting S1PR2 in LX-2 and JS-1 cells. Meanwhile, treatment with JTE-013 or S1PR2 deficiency significantly attenuated liver histopathological injury, collagen accumulation, and the expression of fibrogenesis-associated genes in mice fed a DDC diet. Furthermore, TCAmediated activation of HSCs through S1PR2 was closely related to the yes-associated protein (YAP) signaling pathway via p38 mitogen-activated protein kinase (p38 MAPK). Conclusions TCA-induced activation of the S1PR2/p38 MAPK/YAP signaling pathways plays a vital role in regulating HSC activation, which might be therapeutically relevant for targeting cholestatic liver fibrosis.

Objective:To analyze the clinical features and magnetic resonance imaging of non-malignant patients assigned to Prostate Imaging Reporting And Data System (PI-RADS) 5 score.Methods:We performed a retrospective review of 289 patients who underwent magnetic resonance ultrasound targeted combined system biopsy with PI-RADS 5 lesions in the First Affiliated Hospital of Nanjing Medical University between May 2019 and July 2021. The median age 72 (66, 77)years, median body mass index 24.4(22.3, 27.1)kg/m 2, median prostate volume (PV) 37.39(29.39, 48.86) ml, median PSA 22.24(10.91, 62.69) ng/ml, and median PSAD 0.53(0.30, 1.52)ng/ml 2 were recorded. According to the biopsy pathological results, all patients were divided into benign lesion group and prostate cancer group. PSA, PSAD, PV, and apparent diffusion coefficient (ADC) values were compared, and magnetic resonance imaging and clinical characteristics of patients with biopsy benign lesions were analyzed. Results:There were 11 cases (3.8%) with benign lesion and 278 cases (96.2%) with prostate cancer. The characters of 11 negative biopsy cases were displayed as follows: median age 69(66, 79)years, median body mass index 22.0(21.0, 25.5)kg/m 2, median PV 62.90(38.48, 71.96)ml, median PSA 5.55(2.99, 20.52)ng/ml, median PSAD 0.16(0.07, 0.24) ng/ml 2, median ADC 714.47(701.91, 801.26)×10 -6 mm 2/s, abnormal digital rectal and amination in 5 cases, smoking in 7 cases, and alcohol consumption in 4 cases. The median PV [62.90(38.48, 71.96) vs. 37.21(29.22, 47.82)ml, P<0.01], the PSA value [5.55(2.99, 20.52) vs. 23.53(11.14, 65.98)ng/ml, P<0.01], and the PSAD value [0.16(0.07, 0.24) vs. 0.58(0.31, 1.57)ng/ml 2, P<0.01] were significantly different between benign condition group and prostate carcinoma group. Benign condition group included 5 chronic prostatitis, 2 acute prostatitis (1 with focal adenocarcinoma), 2 granulomatous inflammation, and 2 tuberculous granulomatous inflammation. In 7 benign cases, PSA was less than 10 ng/ml, combined with frequent urination, urgency of urination and incontinence were founded. In 8 benign cases, the area of lesion was more than 50% of the total prostate area in the axial position and the imaging of magnetic resonance were diffused, with regular shape and uniform signal. The imaging of symmetrical distribution was in 6 cases. Conclusions:The benign condition with PI-RADS 5 lesions included chronic prostatitis, acute prostatitis, granulomatous inflammation and tuberculous granulomatous inflammation, among which prostatitis was the most common cause. The PSA value were less than 10 ng/ml in most benign cases, with symptoms such as frequent urination, urgency of urination and incontinence. The imaging of magnetic resonance were diffused, symmetrically distributed, with regular shape and uniform signal.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective:To explore the efficacy of single-plane bi-parameter magnetic resonance imaging (bpMRI) in the diagnosis of prostate cancer.Methods:The clinical data of 343 patients who underwent transperineal template prostate magnetic resonance-transrectal ultrasound (MRI-TRUS) cognitive fusion biopsy at the First Affiliated Hospital of Nanjing Medical University from January 2020 to July 2021 were retrospectively analyzed, with median age of [65.0(59.0, 72.0)] years, median body mass index (BMI) of [24.1(22.2, 25.6)]kg/m 2, median prostate volume (PV) of [41.7(29.1, 53.3)]ml, median PSA[6.9 (5.5, 8.4) ng/ml], median PSAD of[0.17(0.12, 0.22) ng/ml 2], and abnormal rate of digital rectal examination (DRE) [6.4%(22/343)]. All patients underwent initial biopsy and bi-parameter magnetic resonance imaging (bpMRI) examination before biopsy, and the images were interpreted using prostate image reporting and data system version 2.1 (PI-RADS v2.1). The detection rates of prostate cancer and clinically significant prostate cancer (csPCa) were compared between single-plane bpMRI and bpMRI. When PI-RADS≥3 score, MRI results were positive; when PI-RADS ≤2 score, MRI results were negative. Results:In the single-plane bpMRI group, 121 MRI results were negative and 222 were positive. Positive patients included 95 with PI-RADS 3 score, 94 with PI-RADS 4 score, and 33 with PI-RADS 5 score. In bpMRI group, 141 MRI results were negative and 202 were positive. Among the positive patients, 67 patients with PI-RADS 3 score, 102 patients with PI-RADS 4 score, and 33 patients with PI-RADS 5 score. The detection rates of single-plane bpMRI and bpMRI for prostate cancer were 22.3% (27/121) and 15.6% (22/141) in MRI negative cases[22.3% (27/121) and 15.6% (22/141), P=0.17], and PI-RADS scores with 3 points [35.8% (34/95) vs. 44.8% (30/67), P=0.25], 4 points [89.4% (84/94)vs. 90.2% (92/102), P=0.85] and 5 points [90.9% (30/33) vs. 93.9% (31/33), P=1.00] showed no significant difference in stratification. The detection rate of csPCa in the single-plane bpMRI group and bpMRI group was significantly different in the MRI negative cases [7.4% (9/121) and 2.1% (3/141), P=0.04]. PI-RADS scores with 3 points [22.1% (21/95) vs. 29.9% (20/67), P=0.27], 4 points [80.9% (76/94) vs. 79.4% (81/102), P=0.80] and 5 points [84.9% (28/33) vs. 90.9% (30/33), P=0.71] showed no significant difference in stratification. Conclusions:For those suspected of prostate cancer patients with PSA 4-10 ng/ml and PI-RADS score ≥3, single-plane bpMRI or bpMRI examination has the same efficacy in term of the detection rate of prostate cancer and csPCa.

Objective:To explore the optimal core numbers in targeted prostate biopsy (TB).Methods:The clinical data of 138 patients with prostate cancer diagnosed by six needle trans-perineal TB combined with system biopsy in the First Affiliated Hospital of Nanjing Medical University from October 2018 to March 2020 were retrospectively analyzed. Their age was (69.07 ± 7.97) years old, the PSA value was 9.15 (6.66, 12.95) ng/ml, the prostate volume was 35.01 (27.65, 43.27) cm 3and the PSA density was 0.25 (0.17, 0.36) ng/(ml ·cm 3). All patients accepted bi-parametric magnetic resonance imaging examination and had regions of interests (ROIs) with prostate imaging reporting and data system (PI-RADS) version 2.0 scores ≥ 3. The detective rate of prostate cancer (PCa), clinically significant PCa (CsPCa) and clinically insignificant PCa (CIPCa), along with the Gleason score upgrading rate after radical prostatectomy were compared between different numbers of prostate TB cores. Results:The detective rates for present PCa or CsPCa for the first 1-, 2-, 3-, 4-, 5- and 6-core TB were 74.64%(103/138), 85.51%(118/138), 94.20%(130/138), 98.55%(136/138) and 100.00%(138/138) compared with the total number of cores taken, respectively. The detective rates for CsPCa for the first 1-, 2-, 3-, 4-, 5- and 6-core TB were 67.52%(79/117), 77.78%(91/117), 88.89%(104/117), 93.16%(109/117) and 98.29%(115/117) compared with the total number of cores taken, respectively. Additionally, 20.72%(23/111) patients had Gleason score upgrade after RP. Compared with 6-core TB, the rates of postoperative upgrading for the first 1-, 2-, 3-, 4- and 5-core TB were 50.00%(44/88), 67.05%(59/88), 81.82%(72/88), 88.64%(78/88) and 95.45%(84/88), respectively. For the ROIs with PI-RADS score of 3, 4 and 5, the CsPCa detected by 5, 4 and 3 needles of TB were 95.00% (19/20), 94.92% (56/59) and 94.74% (36/38) respectively. Postoperative upgrading rates were 11.11% (2/18), 9.30% (4/43) and 7.41% (2/27) respectively.Conclusions:For ROIs with PI-RADS score of 3, 4 and 5, TB with 5, 4 and 3 cores respectively is enough to obtain higher diagnostic efficiency and accuracy.

Objective:To explore the influencing factors of clinically significant prostate cancer (CsPCa) in patients with PI-RADS score 3.Methods:The data of 133 consecutive patients with the PI-RADS score 3 from January 2019 to December 2020 were retrospectively analyzed. All patients underwent 4-needle transperineal targeted biopsy and 12-needle systematic prostate biopsy (SB). The overall age was 66 (60-72) years, and the overall PSA value was 8.22 (5.95-11.41) ng/ml. All patients underwent multiparametric magnetic resonance imaging (mpMRI), and PI-RADS v2.0 score was 3. Patients were divided into two mutually exclusive groups: non CsPCa group and CsPCa group. The differences of lesion location, laterality, focality and sequence parameters of mpMRI between the two groups were compared, and multivariate binary logistic regression was used to analyze the independent predictors of PI-RADS score 3 in patients with CsPCa.Results:Biopsy results showed 57 cases of prostate cancer, including 41 cases of CsPCa, and 76 cases of non-prostate cancer. The detection rate of prostate cancer was 46.62 %(57/133), and the detection rate of CsPCa was 30.83 %(41/133). There were 41 cases in CsPCa group and 92 cases in non CsPCa group. There was no significant difference between CsPCa group and non CsPCa group in age [66 (58-70) years vs. 66 (60-72) years], body mass index [24.22 (21.82-25.71) kg/m 2 vs. 23.71 (21.99-26.12) kg/m 2], PSA [9.39 (6.35-12.55) ng/ml vs. 7.67 (5.83-10.51) ng/ml], abnormal rate of rectal digital examination [21.95% (9/41) vs. 9.78% (9/92)] (all P > 0.05). There was significant difference in PSAD [0.40 (0.16-0.65) ng/ml 2 vs. 0.17 (0.12-0.24) ng/ml 2] ( P<0.05). In MRI, PI-RADS=3 lesions were mainly located in the transitional zone [46.62 %(62/133)]. In CsPCa group, MRI lesions were located in peripheral zone in 16 cases, transitional zone in 19 cases, and both areas in 6 cases. There were 16 cases on the right, 15 cases on the left and 10 cases on both sides. The lesions were diffused in 19 cases and localized in 22 cases. In the non CsPCa group, 41 lesions were located in the peripheral zone, 43 in the transitional zone, and 8 in both areas. There were 26 cases on the right, 35 cases on the left and 31 cases on both sides. The lesions were diffuse in 56 cases and localized in 36 cases. There was no significant difference in lesion location, side and diffusion degree between the two groups ( P> 0.05). Compared with the non CsPCa group, the positive rate of all MRI sequences in CsPCa group was higher (82.93% vs. 40.22%, P < 0.001), the positive rate of T2 weighted imaging (T2WI) was higher (92.68% vs. 75.00%, P = 0.018), the positive rate of diffusion weighted imaging (DWI) was higher (90.24% vs. 56.52%, P < 0.001), the maximum diameter was larger[(0.67(0.30-1.19)mm vs. 0.48(0.20-0.62)mm, P < 0.001], and the apparent diffusion coefficient (ADC) was lower[0.70(0.61-0.87) vs. 1.10(0.86-1.50), P < 0.001]. Concurrently, PSAD and lesion ADC were important predictors of CsPCa in logistic regression model [mean 10 fold cross validation AUC: 0.78(95% CI 0.65-0.88)]. Conclusions:Most of the MRI lesions in patients with PI-RADS 3 were located in the transitional zone, and the MRI lesions in CsPCa were more obvious and diffusion limited. PSAD and ADC values are independent predictors for the diagnosis of CsPCa in patients with PI-RADS score 3, and the log 2PSAD-ADC prediction model is helpful to find CsPCa from patients with PI-RADS score 3 and protect patients from unnecessary biopsy.