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.

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.

Objective:To demonstrate the polymorphism of α chain of bovine major histocompatibility complex(BoLA)classⅠmolecule and domain binding constant chain(Ii).Methods:Total 75 BoLA Iα genes were obtained from three Huaibei cattle and analyzed by molecular biology software;the genes of typical BoLA Iα domains and Ii were cloned,and then inserted into prokaryotic expression plasmid.After induced protein expression;the domains of BoLA Ⅰα chain binding to Ii were detected by pull-down meth-od and Western blot.The recombinant eukaryotic expression plasmids were constructed and the co-localization of BoLA Iα segments with Ii was observed by laser confocal microscopy.Results:Firstly,it was found that there were at least 5 kinds of BoLA Iα in the cloned gene sequence,which were highly polymorphic and they were mainly distributed in the antigen peptide binding region(PBR)of BoLA Ⅰ(α1α2)and cytoplasmic region.Secondly,the prokaryotic recombinant plasmids containing BoLA Ⅰα1α2α3,BoLA Ⅰα1α2 or BoLA Ⅰα 3 were constructed,then they were respectively induced to express and purified,in which,the BoLA Ⅰα1α2α3 and BoLA Ⅰα1α2 had the activity of binding to Ii.Finally,in 293T cells BoLA Ⅰα1α 2α3 or BoLA Ⅰα1α2 was found that could co-localize with Ii,while a single BoLA Ⅰα3 could not.Conclusion:BoLA Ⅰα gene is highly polymorphic.BoLA Ⅰα1α2 is a func-tional fragment that binds to Ii and co-locates intracellular.

In recent years, ultrasonography has been more and more widely applied in the diagnosis and treatment of skin diseases, as well as in the field of aesthetic dermatology. Compared with physical examination, ultrasonography can more intuitively reflect the normal structures of skin soft tissues, and be used to more objectively assess deeper skin lesions, showing great application prospects in dermatology. This article provides an overview of the advances in the application of ultrasonography in the field of dermatology.

Objective To explore the effect of nicotinamide transmethylase on intracellular reactive oxygen species(ROS)in iron death of hepatocellular carcinoma cells and its mechanism.Methods Methyl nicotinamide(MNA)expression in cells was detected using a tandem liquid chromatography-mass spectrometry.The average fluorescence intensity of ROS and lipid peroxidation was measured using a flow cytometer.Western blot was used to detect changes in the expression of human liver cancer cells(SK-Hep-1,Hep3B).Forty patients with primary hepatocellular carcinoma who received treatment in our hospital from March 2019 to February 2020 were selected as the study subjects,and their adjacent tissue samples and liver cancer tissue samples were collected.Immunohistochemical methods were used to detect the levels of nicotinamide N-methyltransferase(NNMT)and ROS in adjacent and liver cancer tissues.CCK-8 method was used to detect the survival activity of cells with different iron concentrations.Results The MNA levels in the liver cancer tissue group were higher than those in the adjacent tissue group(P<0.05).Compared with the adjacent tissue group,the average fluorescence intensity expression of ROS in the liver cancer tissue group increased,while the average fluorescence intensity expression of lipid peroxidation decreased(P<0.05).Compared with the adjacent tissue group,the expression levels of SK Hep-1 and Hep3B cells in the liver cancer tissue group increased(P<0.05).Compared with the control group,NNMT groups 2,10,20,and 25 μmol/L The cell survival activity level increased(P<0.05);Compared with the NNMT group,the iron inhibition group had different iron concentrations(2μmol/L,10μmol/L,20μmol/L,25μmol/L.The expression of cell viability decreased(P<0.05).Conclusion ROS mediated by nicotinamide methyltransferase can be guided to produce ROS and energy disorders,leading to increased tumor cell death.

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.

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

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 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.

In recent years, the incidence of single-gene nephrolithiasis has been increasing year by year. With the application of whole-genome analysis and whole-exome sequencing technology, the etiology of single-gene mutations leading to the development of urinary calculi has been extensively verified. Therefore, this article reviews the research on urinary calculi-related genetic diseases at home and abroad, and introduces transport proteins and channels; ions, protons and amino acids. The role of urinary calculi in the majority of clinicians realizes the significance of genetic testing in such diseases, thereby increasing the understanding of genetically related urinary calculi and improving the level of clinical diagnosis and treatment.