ObjectiveTo elucidate the chemical composition of Danshenyin and its blood components in rats after oral administration. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） coupled with PeakView 1.2 software was used to systematically characterize and identify the components of Danshenyin aqueous extract and its migratory components in rat blood after oral administration based on the retention time， quasi-molecular ion peaks， secondary fragmentation ions， and literature reports， and a preliminary compounds identification of Salviae Miltiorrhizae Radix et Rhizoma aqueous extract， the co-decoction of Santali Albi Lignum and Amomi Fructus was carried out to attribute the chemical constituents of the aqueous extract of Danshenyin. ResultsA total of 73 compounds， including 21 phenolic acids， 23 diterpenes， 6 flavonoids， 7 organic acids， 3 volatile oils and 13 others， were identified from the aqueous extract of Danshenyin. And 36 prototypes and 15 metabolites were identified in rat plasma， the major metabolic pathways included reduction， hydration， hydroxylation， demethylation， methylation， sulfation and others， these metabolites were mainly derived from tanshinones and salvianolic acids. ConclusionThe main blood components of the aqueous extract of Danshenyin are salvianolic acids and tanshinones， which may be the material basis of the efficacy. This study can provide reference for pharmacological research， quality control， and clinical application of Danshenyin.

Objective To investigate the relationship between mean platelet volume/lymphocyte ratio(MPVLR)and left atrial thrombosis in elderly patients with non-valvular atrial fibrillation(NVAF).Methods A total of 178 elderly patients with NVAF admitted to the hospital from January 2019 to December 2022 were enrolled in the study.The patients were divided into thrombosis group(28 cases)and non-throm-bosis group(150 cases)according to the left atrial thrombosis judged by using esophageal echocardiography(TEE).The white blood cell count(WBC),red blood cell count(RBC),lymphocyte count,lymphocyte pro-portion,platelet count(PLT)and mean platelet volume(MPV)were detected by automatic blood cell analy-zer,and MPVLR was calculated.The liver and kidney function indicators and blood lipid indicators were detec-ted by automatic biochemical analyzer.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of MPV,lymphocyte ratio and MPVLR for left atrial thrombosis in NVAF patients.Multiva-riate Logistic regression was used to analyze the influencing factors of left atrial thrombosis in elderly NVAF patients.Results MPV,lymphocyte proportion and MPVLR in the thrombosis group were higher than those in the non-thrombosis group,and the differences were statistically significant(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of MPV,lymphocyte ratio and MPVLR for predicting left atrial thrombosis in NVAF patients were 0.821(95％CI:0.764-0.882),0.771(95％CI:0.714-0.842)and 0.901(95％CI:0.861-0.949).respectively.The course of disease in the thrombosis group was longer than that in the non-thrombosis group,the proportion of patients with chronic heart failure,the proportion of patients with stroke,CH A2DS2-VASc score,LAEF,LAD,LVEDV,MPVLR,serum uric acid,MPV,lymphocyte proportion and MPVLR were higher than those in the non-thrombosis group,and LVEF was lower than that in the non-thrombosis group,the differences were statistically significant(P＜0.05).Multivariate Logistic regression a-nalysis showed that disease duration ≥1.93 years(OR=3.050,95％CI:1.928-4.824),chronic heart failure(OR=3.333,95％CI:1.808-6.144),MPVLR≥3.10(OR=3.873,95％CI:1.734-8.650)were independ-ent risk factors for left atrial thrombosis in elderly NVAF patients(P＜0.05).Conclusion The increase of MPVLR is associated with left atrial thrombosis in elderly patients with NVAF,and it can be used as a an in-dicator to predict left atrial thrombosis in patients with NVAF.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Golgi protein 73 (GP73) is a Golgi transmembrane protein that can be released into blood by cleavage. An increasing number of studies have shown that the increase in serum GP73 is closely associated with the development and progression of nonalcoholic fatty liver disease (NAFLD) and serum GP73 is expected to be used as a potential serological marker for the diagnosis and assessment of NAFLD. This article reviews the research advances in serum GP73 in NAFLD and analyzes its potential mechanism of action, so as to provide new options for the therapeutic targets of NAFLD.

Five new racemic N-acetyldopamine (NADA) trimers, asponchimides A-E (1-5), were isolated from Aspongopus chinensis, a prominent traditional Chinese medicinal insect employed for alleviating pain, treating indigestion, and addressing kidney ailments. Compounds 1-5 were successfully resolved by chiral high-performance liquid chromatography (HPLC), yielding five pairs of enantiomers: (+)- and (-)-asponchimides A-E (1a/1b-5a/5b). Their structural identities were discerned by extensive spectroscopic analyses, including high-resolution mass spectrometry (HRMS), ultraviolet-visible (UV-Vis) spectroscopy, infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR), and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. Compounds 1-5 are pioneering instances of NADA trimers featuring a Δ⁷ double bond. When subjected to a series of bioassays, a majority of the compounds exhibited weak inhibitory activity against nitric oxide (NO) production in LPS-induced RAW 264.7 cells.
Molecular Structure ; Magnetic Resonance Spectroscopy ; Dopamine ; Nitric Oxide

Objective:To compare the clinical efficacy and safety of Shuo Tong ureteroscopy(ST-URS) and flexible ureteroscope(FURS)combined with holmium laser lithotripsy in the treatment of upper ureteral calculi with CT numerical value ≥ 1000 HU.Methods:A retrospective analysis of the clinical data of patients of upper ureteral calculi with CT numberical value≥1000 HU in the First Affiliated Hospital of Xiamen University was made from January 2018 to November 2020.There were 61 cases treated with ShuoTong ureteroscopy holmium laser lithotripsy (ST-URS group), including 45 males and 16 females, with 40 on the left and 21 on the right, age of(48.3±12.7) years, body mass index of(24.7±2.7)kg/m 2, the diameter of stone of(1.50±0.45)cm, and the CT numberical value of(1 288.8±179.0)(1 017-1 738)HU. There were 87 cases were treated with flexible ureteroscopy holmium laser lithotripsy (FURS group), including 58 males and 29 females, with 56 on the left and 31 on the right, age of(48.5±13.0) years, body mass index of(24.1±3.8)kg/m 2, the stone diameter of(1.45±0.40)cm, and the CT numberical value of(1 311.3±188.9)(1 009-1 817)HU. There were no significant differences in gender, age, body mass index, the location of stone, the diameter of stone and the CT numberical value of stone( P>0.05)between the two groups. For ST-URS group, a rigid ureteral channel sheath and standard mirror(F7.5/11.5)were placed under direct vision, exiting the standard mirror, leaving the channel sheath, inserting a lithotripsy mirror(F4.5/6.5)and a holmium laser[Power: 8-30 W(0.4-1.0 J/20-30 Hz)], and withdrawing the stone fragments after crushing the stone by "nibbling method" . For FURS group, a hard ureteroscope(F8/9.8)was used to explore the lesion side of the ureter, inserting a guide wire and placing a soft ureteral sheath, then inserting a flexible ureteroscope(F8)for holmium laser lithotripsy, and useing a stone basket to remove larger stone fragments. Ureteral stent was routinely indwelled after the operation. On the day 1 and 1 month after the operation, imaging examinations were performed to evaluate the stone-free rate. No residual stones or the diameter of stone was ≤0.4 cm and no urinary tract infection or any symptoms were defined as stone free. The operation time, blood loss, success rate of stage Ⅰ ureteral access sheath placement, incidence of postoperative complications, stone-free rate(SFR) at 1 day after operation, SFR at 1 month after operation, postoperative hospital stay and hospitalization costs were compared between the two groups. According to the size of calculi, the 2 groups were divided into 2 subgroups(≥1.5 cm and <1.5 cm)in order to make further analysis. The operation time, stone-free rate(SFR) at day 1 after operation and SFR at 1 month after operation were compared between the two groups. Results:The operation time of the ST-URS group was shorter than the FURS group(40.10 min vs. 49.43 min, P=0.020), and the incidence of postoperative complications was lower than the FURS group[3.28%(2/61)vs. 13.79%(12/87), P=0.031]. The SFR at day 1 after operation was significantly higher than the FURS group[60.7%(37/61)vs. 25.3%(22/87), P<0.01], and the hospitalization cost was lower than that of the FURS group(27 686 yuan vs. 32 281 yuan, P<0.010). There were no significant differences in the blood loss[(4.92±9.51)ml vs.(3.95±6.04)ml, P=0.452], success rate of stageⅠureteral access sheath placement[ 96.7%(59/61)vs. 96.6%(84/87), P=1.000], SFR at 1 month after operation[81.97%(50/61) vs. 75.86%(66/87), P=0.375] and postoperative hospital stay[(2.5±1.4)d vs.(2.4±0.8)d, P=0.543] between the two groups. When the size of calculi was ≥1.5cm, the operation time of the ST-URS group was shorter than the FURS group (43.67 min vs 55.00 min), the SFR at 1 day after operation was higher than the FURS group[40.00%(12/30)vs. 9.38%(3/32)], and the above differences are all statistically significant ( P<0.05). Conclusions:Compared with the FURS, for the treatment of upper ureteral calculi with CT numerical value ≥1000 HU, the ST-URS has shorter in operative time, lower in hospitalization cost and incidence of postoperative complications and higher SFR at day 1 after operation. The ST-URS is a safe and effective surgical technique, which is superior in the treatment of larger(≥1.5 cm) stones.

Objective:To evaluate the relationship between the mechanism underlying the antidepressant effect of S-ketamine and hippocampal gamma-aminobutyric acid B receptor (GABA BR) in mice. Methods:A total of 54 male C57BL/6(B6) mice, aged 8 weeks, weighing 25-30 g, were used in this study. Forty mice were selected to develop the depression model by chronic social defeat stress. Twenty-six depression-susceptible mice were screened out by social avoidance test at day 11 after developing the model and divided into 2 groups ( n=13 each) by a random number table method: depression-susceptible group (Sus group) and depression-susceptible + S-ketamine group (Sus + S-ket group). The remaining 14 mice served as control group (C group). Starting from day 12 after developing the model, S-ketamine 10 mg/kg was intraperitoneally injected every day for 3 consecutive days in Sus+ S-ket group, while the equal volume of normal saline was given instead in C group and Sus group. The open field test was performed at 1 h after the last administration, and the total distance of movement was recorded. The forced swimming test was performed at 1 day after the open field test, and the immobile time was recorded. The sucrose preference test was performed to calculate the proportion of sucrose consumption at 1 day after the forced swimming test. One hour after the end of behavioral test, mice were sacrificed, and the hippocampal tissues were removed. Western blot was used to detect the expression of GABA BR1, GABA BR2, mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), phosphorylated TrkB (p-TrkB), glutamate receptor 1 (GluR1) and postsynaptic dense protein 95 (PSD95). The p-mTOR/mTOR ratio and p-TrkB/TrkB ratio were calculated. The fluorescence intensity of BDNF in hippocampal CA1 region was detected by immunofluorescence. The number of dendritic spines in hippocampal CA1 region was measured by Golgi staining. Results:In the open field test, no statistically significant difference in the total distance was detected among the three groups ( P>0.05). Compared with C group, the immobile time in the forced swimming test was significantly prolonged, the proportion of sucrose consumption was decreased, the expression of hippocampal GABA BR1, GABA BR2, BDNF, GluR1 and PSD95 was down-regulated, and the ratios of p-mTOR/mTOR and p-TrkB/TrkB were decreased, the fluorescence intensity of BDNF and total number of dendritic spines in the hippocampal CA1 region were decreased in Sus group ( P<0.05), and no significant change was found in the parameters mentioned above in Sus+ S-ket group ( P>0.05). Compared with Sus group, the immobile time in the forced swimming test was significantly shortened, the proportion of sucrose consumption was increased, the expression of hippocampal GABA BR1, GABA BR2, BDNF, GluR1 and PSD95 was up-regulated, the ratios of p-mTOR/mTOR and p-TrkB/TrkB were increased, and the fluorescence intensity of BDNF and total number of dendritic spines in the hippocampal CA1 region were increased in Sus+ S-ket group ( P<0.05). Conclusions:The mechanism underlying the antidepressant effect of S-ketamine may be related to up-regulation of hippocampal GABA BR expression, activation of mTOR-BDNF signaling pathway, and improvement in synaptic plasticity in mice.

【Objective】 To investigate the clinical value of transrectal contrast-enhanced ultrasound (CEUS) in the diagnosis of prostate cancer in different total prostate specific antigen (tPSA) intervals. 【Methods】 According to serum tPSA levels, 96 patients meeting the inclusion criteria were divided into 3 groups:4-10 ng/mL, >10-20 ng/mL and >20 ng/mL groups. All patients underwent transrectal CEUS. With pathological results as reference, the diagnostic value of transrectal CEUS in different tPSA intervals was evaluated. 【Results】 Of the 96 cases, 62 were confirmed by pathology as prostate cancer and 34 as benign prostatic hyperplasia (BPH). The main perfusion characteristics of prostate cancer under CEUS were rapid enhancement (64.52%), rapid clearance (70.97%), uneven enhancement (83.87%) and high enhancement (61.29%);the main characteristics of BPH were non-rapid enhancement (70.59%), non-rapid clearance (73.53%), uniform enhancement (76.47%) and non-high enhancement (52.94%). There were significant differences in terms of enhancement speed, clearance speed and enhancement uniformity between prostate cancer and BPH (P<0.05), but no significant difference in the enhancement intensity. The sensitivity of transrectal CEUS in the diagnosis of prostate cancer in low, medium and high tPSA groups were 58.33%, 70.37% and 95.65%, the specificity were 83.33%, 76.92% and 66.67%, and the accuracy were 73.33%, 72.50% and 92.31%, respectively. Transrectal CEUS showed consistency at different serum tPSA levels for the diagnosis of prostate cancer, with statistical significance. Moreover, in the 4.0 ng/mL ≤tPSA<10.0 ng/mL group, the diagnostic specificity was the highest. 【Conclusion】 Transrectal CEUS is helpful in the differential diagnosis of benign and malignant prostatic lesions, especially for patients with different serum tPSA levels.

Objective To evaluate the differences in efficacy,safety and economics of vancomycin hydrochloride for injection between two manufacturers based on real-world data.Methods A total of 6 757 cases of intravenous use of vancomycin hydrochloride for injection from different manufacturers between January 1,2013 and December 31,2019 in the Affiliated Drum Tower Hospital of Nanjing University Medical School were retrospectively analyzed,and 5308 cases were matched by 1∶1 propensity score method,including 2 654 cases in the group A(domestic drug group)and 2 654 cases in group B(the innovator drug group).The differences in efficacy and safety between the two groups were compared.Cost-effectiveness analysis was used to compare the drug economics of the two groups.Results There were no significant differences in clinical cure rate,bacterial clearance rate,and incidence of adverse events between the two groups(P>0.05).In terms of economics,the average cost of vancomycin per capita,average daily cost of vancomycin and average cost of antibiotics per capita were significantly different between the two groups(P<0.05),and the cost of group B was higher than that of group A.Conclusion The efficacy and safety of vancomycin hydrochloride for injection were consistent between the two manufacturers.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone