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 compare the effects of different statistical protocols on the results of external quality assessment(EQA)of se-men,and select appropriate statistical protocols for the promotion of EQA of semen.Methods Taking sperm concentration as an ex-ample,the semen EQA data of 20 laboratories in Hunan Province in 2022 were selected,and the advantages and disadvantages of the traditional statistical scheme(TSS),robust statistical scheme(RSS)and traditional statistical scheme after eliminating the"outliers"(TSEOS)combined with robust statistical technology were analyzed and compared.Results The"outliers"could not be excluded from the sperm concentration data of the four groups in the TSS,which led to the difference between TSS and RSS or TSEOS.The num-ber of qualified laboratories for TSS and RSS were 19 vs 16,19 vs 16,19 vs 19,and 19 vs 19,respectively.Conclusion The results of RSS are similar to those of TSEOS.Compared with TSS,RSS do not need to remove outlier data steps,and are more suitable for se-men EQA data analysis with small data volume.

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 establish surgical difficulty scoring system of partial nephrectomy based on holographic imaging and explore its application value in partial nephrectomy.Methods:A total of 184 patients including 110 males and 74 females with renal tumors diagnosed as stage cT 1 to cT 2 before surgery in the First Affiliated Hospital of Xiamen University from October 2019 to January 2022 were included. Among the 184 patients, 141 patients were treated with partial nephrectomy and 43 patients were treated with radical nephrectomy (3 partial nephrectomies were finally changed to radical nephrectomies due to vascular and tumor location). 60 patients had hypertension. 24 patients had diabetes. 7 patients had hyperuricemia. The median age was 55(47, 62) years. The median BMI was 23.7(21.8, 26.4) kg/m 2. The median maximum tumor diameter was 3.9(2.9, 5.2) cm. The median preoperative eGFR was 99.7(83.4, 114.2) ml/(min·1.73m 2). The median R. E.N.A.L. score was 8(6, 9). The median PADUA score was 9(8, 10). 153 patients were diagnosed as stage cT 1 and 31 patients were diagnosed as stage cT 2. The hologram reconstruction was performed according to preoperative CT or MRI examination. The maximum diameter of the tumor in the kidney (D), the compression degree of the renal segmental vessels by tumor(C), the area of the renal sinus occupied by tumor(O) and the mass of exophytic rate(M) were comprehensively considered and finally constituted the difficulty scoring system named DCOM score for partial nephrectomy. The DCOM score divided the complexity of tumor surgery into mild (4-6 points), moderate (7-8 points) and high (≥ 9 points). Meanwhile, the MIC (surgical margins are negative, WIT is <20 min, and no major complications)was used to evaluate the overall surgical effect. The DCOM, R. E.N.A.L. and PADUA scores were performed on all patients and compared with each other to evaluate the surgical effect of DCOM score in partial nephrectomy. Results:All surgeries in this study were successfully completed, including 141 partial nephrectomies and 43 radical nephrectomies. The DCOM score was 10(9, 11) for radical nephrectomy and 6(5, 8) for partial nephrectomy, and the difference was statistically significant ( P=0.001). There were 23 patients (37.7%) in highly complex group, 39 patients (88.6%) in moderately complex group and 79 patients (100.0%) in mildly complex group underwent partial nephrectomy, respectively. According to multifactorial analysis, patients in highly and moderately complex group of DCOM score had 8.88 times ( P=0.001) and 1.76 times ( P=0.005) less reach MIC than those in mildly complex group, respectively. Patients in highly and moderately complex group of PADUA score had 4.86 times ( P=0.005)and 3.41 times ( P=0.006)less reach MIC than patients in mildly complex group of DCOM score, respectively. What’s more, patients in moderately complex group of R. E.N.A.L. score had 3.11 times ( P=0.003) less reach MIC than patients in mildly complex group of DCOM score. In the ROC curves to predict MIC achievement, the AUC values of R. E.N.A.L., PADUA and DCOM scores were 0.657, 0.655 and 0.746, respectively. Comparing:R. E.N.A.L. score with DCOM score, the AUC value was statistically significant ( P=0.025). Conclusions The surgical difficulty scoring system (DCOM score) based on holographic imaging can predict the outcome of partial nephrectomy, but further verification is needed.

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

Objective To evaluate the clinical application of early total care (ETC) for polytrauma patients combined with thoracolumbar fractures.Methods A retrospective case control study was conducted to analyze the clinical data of 137 polytrauma patients combined with thoracolumbar fractures admitted to the First Affiliated Hospital of Soochow University and the Third People's Hospital of Zhang,jiagang from January 2012 to October 2015.There were 90 males and 47 females,aged 26-69 years,with an average age of 48.2 years.The patients were divided into ETC group (n =59) and TMC group (n =78).In the ETC group,physicians from different departments evaluated the patients and developed individualized therapeutic regimens to allow the patients to undergo surgery at early stage after injury.The TMC group preferentially stabilized the patient's condition or transferred the patients to specialist treatment,and then the surgery was performed electively after the condition of the patient was stable.The ISS of the ETC group was (22.15 ± 9.28)points,and that of the TMC group was (23.37 ± 10.74) points.All patients underwent conventional posterior pedicle screw internal fixation.For patients with burst fracture and nerve injury,posterior spinal canal decompression was performed.The thoracolumbar injury classification and severity score (TLICS),spinal load sharing classification (LSC),preoperative and postoperative Glasgow coma score (GCS),Frankel classification,hospitalization time and postoperative complications were compared between the two groups.Results The TLICS scores of ETC group were significantly lower than those of TMC group (P ＜ 0.05) while the LSC scores showed no significant differences between the two groups (P ＞ 0.05).ETC group had shorter hospitalization time [(11.8 ± 3.7)days ∶ (17.5 ±4.5)days] and lower pressure ulcer incidence [(5％ ∶ 21％)] than the TMC group (P ＜ 0.05 or 0.01),but the former had significantly higher wound infection rate [(17％ ∶ 15％)] (P ＜ 0.05).There was no significant difference in pulmonary infection and deep venous thrombosis incidence between the two groups (P ＞ 0.05).No significant differences were found in the preoperative GCS scores between the two group (P ＞ 0.05) while the postoperative GCS scores of TMC group were higher than those of ETC group (P ＜ 0.01).Postoperative GCS scores in both groups were significantly higher than their preoperative GCS (P ＜ 0.05).The results of postoperative Frankel classification in the ETC group were as follows:Grade A in one patient,Grade B in one,Grade C in three,Grade D in four and Grade E in two patients,with an improvement rate of 82％.The results of postoperative Frankel classification in the TMC group were as follows:Grade A in three patients,Grade B in three,Grade C in three,Grade D in four and Grade E in four,with an improvement rate of 65％.Conclusions For polytrauma patients combined with thoracolumbar fractures,ETC can shorten hospitalization time,reduce the pressure ulcer incidence,and better facilitate the recovery of nerve function,yet with higher wound infection risk compared with TMC.TMC was preferred subjectively for patients with unstable thoracolumbar fractures and high TLICS.

Objective To investigate the pharmacy practice of clinical pharmacists' attendance in the treatment of adverse reactions caused by drug interactions. Methods Analysis was conducted on the causes and treatment of hypertension in one pedinatric patient with aplastic anemia induced by combined use of cyclosporine and voriconazole. Results Cyclosporine A could lead to prolonged hypertension.Cyclosporine A dosage should be adjusted;antihypertensive drugs should be used in necessity.When choosing antihypertensive drugs,drug interaction with cyclosporine A should be considered. Conclusion Clinical pharmacists could manage adverse drug reactions by analyzing drug interactions,and offer suggestions for ADR patients.

Objective To investigate the natural infection of Theiler's murine encephalomyelitis virus (TMEV) in mice,and to survey the distribution of virus in tissues and the changes of serum antibody in the experimentally TMEV-infected mice.Methods Enzyme linked immunosorbent assay (ELISA) and fluorescence quantitative RT-PCR (qRT-PCR) assay were used to detect the antibody and nucleic acid of TMEV in clinical samples.These samples included SPF mice collected from Guangdong area in 2010-2015,mice obtained from a non-barrier laboratory rodent colony,and wild Rattus norvegicus live-trapped around the non-barrier laboratory rodent colony.36 ICR mice were intracerebrally inoculated with TMEV BeAn strain.The clinical signs of the animals were observed daily post-inoculation.Three mice were euthanatized at day 0,3,7,10,17,21,31,39 and 46 post-inoculation (dpi),respectively.Tissue and serum samples were collected for TMEV detection.Results The TMEV antibody and nucleic acid positive rates of SPF mice collected from Guangdong area in 2010-2015 were 5.29％ (n=2834) and 27.27％ (n=457),respectively.The TMEV antibody and nucleic acid positive rates of the mice obtained from a non-barrier laboratory rodent colony were 71.95％ (n=82) and 53.66％ (n=82),respectively.The TMEV nucleic acid positive rate of wild Rattus norvegicus was 25.93％ (n=27).In the TMEV positive mice,only two mice showed obvious clinical symptoms.The cecal contents,feces and brain samples were the best candidates for qRT-PCR assay.The viral nucleic acid could be detected in the brain,heart,liver,lung and stomach of ICR mice at 3 dpi,but no viral nucleic acid was detected in the spleen,kidney,and cecum.The viruses in liver,heart,lungs and stomach were completely cleared at 10 dpi,and the viruses persisted in the brain throughout the experiment.The TMEV antibody could be detected at 7 dpi,and then the antibody positive rate reached 100％ at 17 dpi.The antibody level increased gradually and maintained up to 46 days.ICR mice showed latent infection after TMEV inoculation,with no obvious symptoms and eye pathological changes.Conclusions The experimental mice and wild Rattus norvegicus in Guangdong area are both infected with TMEV,and the infection rate is high.The mice inoculated with TMEV BeAn strain show latent infection.The TMEV antibody produced in mice can be detected at 7 dpi and persisted until the end of the experiment.The viruses are found in the liver,heart,lung and stomach for a short time,but are persisted in the brain for a long time.There is a good consistency of TMEV detection between qRT-PCR and ELISA.The qRT-PCR assay can be used as a powerful complement method for the national standard of laboratory animals.

BACKGROUND:For the treatment of distal tibial fractures, open reduction and plate fixation, minimal y invasive percutaneous plate fixation and intramedul ary nail fixation are effective, but each has advantages and disadvantages. OBJECTIVE:To compare the effects of intramedul ary nail combined with blocking screws versus minimal y invasive percutaneous plate fixation in treating distal tibial fractures. METHODS:Fifty-one cases of distal tibial fractures were divided into two groups. The blocking screw group (23 cases) was treated with closed reduction and internal fixation with interlocking nail combined with blocking screws. The plate fixation group (28 cases) was treated with minimal y invasive percutaneous plate fixation. Fracture healing time, recovery of tibial function and complication occurrence were observed during fol ow-up. RESULTS AND CONCLUSION:Al patients were fol owed up for 8 to 32 months. (1) Except one patient in the plate fixation group, the other patients had bony union. The healing time was (4.6±1.7) months in the blocking screw group and (6.9±2.3) months in the plate fixation group. Significant differences in healing time were detected between the two groups (P<0.05). (2) The excel ent and good rate of tibial function recovery was significantly higher in the blocking screw group (100%) than in the plate fixation group (82%) (P<0.05). (3) No significant difference in the incidence of adverse events was determined between the blocking screw group (13%) and plate fixation group (18%) (P>0.05). (4) Results suggested that interlocking intramedul ary nail combined with blocking screw fixation in the treatment of distal tibial fractures can promote fracture healing and joint function recovery.