Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

Humans ; Adolescent ; Acne Vulgaris/therapy* ; Skin Care ; Surveys and Questionnaires ; Cognition ; China ; Skin

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To deeply explore the principles of drug combinations in the treatment of vitiligo by traditional Chinese medicine master XUAN Guo-Wei by data mining technology,and to analyze the potential mechanism of action of the core drug pairs by network pharmacology.Methods The original case records of Professor XUAN Guo-Wei in treating vitiligo were compiled,and then TCM inheritance Computing Platform was used to analyze the frequency of drugs in the prescriptions,the association rules between drugs,and the core combinations of drugs by the association rule method,and the core drug pairs of Professor XUAN Guo-Wei's treatment of vitiligo were obtained based on the results of the data mining,additionally,the mechanism of the core pairs of drugs was analyzed by using the method of network pharmacology.Results A total of 243 prescriptions were collected,among which the high-frequency drugs were Glycyrrhizae Radix et Rhizoma,Tribuli Fructus,Ecliptae Herba,Cuscutae Semen,Scrophulariae Radix,Angelicae Dahuricae Radix,etc.,and the core pair was Tribuli Fructus-Ecliptae Herba.The main components of Tribuli Fructus-Ecliptae Herba for the treatment of vitiligo were quercetin,kaempferol,etc.,there were 47 targets for the intersection of the active ingredients with the disease,among which TP53,TNF,IL-1β,CASP3,VEGFA,PTGS2,IL10,IL2,IFNG,and IL4 may be the core targets for the treatment of vitiligo by Tribuli Fructus-Ecliptae Herba.The main pathways of Tribuli Fructus-Ecliptae Herba drug pairs against the disease were PI3K-Akt signaling pathway,NF-κB signaling pathway,JAK-STAT signaling pathway and MAPK signaling pathway.Conclusion The core drug pair of Professor XUAN Guo-Wei in the treatment of vitiligo is Tribuli Fructus-Ecliptae Herba,which involves targets such as TP53,TNF,IL-1β,CASP3,VEGFA,PTGS2,IL10,IL2,IFNG,IL4,etc.,Tribuli Fructus-Ecliptae Herba drug pair maybe exert an effect in the treatment of vitiligo through PI3K-Akt signaling pathway,NF-κB signaling pathway,JAK-STAT signaling pathway and MAPK signaling pathway.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To investigate the clinical efficacy of oblique lumbar interbody fusion(OLIF)combined with poste-rior percutaneous internal fixation in patients with lumbar spinal stenosis with or without redundant nerve roots(RNRs).Meth-ods A retrospective analysis of 92 patients with lumbar spinal stenosis treated by oblique lateral lumbar interbody fusion com-bined with posterior percutaneous internal fixation from June 2019 to June 2022 was performed.There were 32 males and 60 females,aged from 44 to 82 years old with an average of(63.67±9.93)years old.All patients were divided into RNRs positive group and RNRs negative group according to redundancy or not before operation.There were 38 patients in RNRs positive group,including 15 males and 23 females.The age ranged from 45 to 82 years old with an average of(65.45±10.37)years old.The disease duration was 24.00(12.00,72.00)months.There were 54 patients in RNRs negative group,including 17 males and 37 females.The age ranged from 44 to 77 years old with an average of(62.42±9.51)years old.The disease duration was 13.50(9.00,36.00)months.The general data of patients were recorded,including operation time,intraoperative blood loss and complications.The imaging parameters before and after operation were observed,including the number of stenosis segments,intervertebral space height,lumbar lordosis angle and dural sac area.The visual analogue scale(VAS)was used to evaluate the back and lower extremity pain,and the Oswestry disability index(ODI)was used to evaluate the activities of daily living.Results All patients were followed up for 8 to 18 months with an average of(11.04±3.61)months,and no complications were found during the follow-up period.The number of stenosis segments in RNRs positive group(1.71±0.46)was more than that in RNRs negative group(1.17±0.38).In RNRs positive group,intervertebral space height,dural sac area,low back pain VAS,lower extremity pain VAS,ODI score were(1.11±0.19)cm,(0.46±0.17)cm2,(5.39±1.00)scores,(5.05±1.01)points,(55.74±4.05)points,respectively.RNRs negative groups respectively(0.97±0.23)cm,(0.69±0.26)cm2,(4.50±0.77)scores,(4.00±0.58)scores,(47.33±3.43)％.In RNRs positive group,intervertebral space height,dural sac area,low back pain VAS,leg pain VAS,ODI score were(1.60±0.19)cm,(0.74±0.36)cm2,(3.39±0.72)scores,(3.05±1.01)scores,(46.74±4.82)scores,respectively.RNRs negative groups respectively(1.48±0.25)cm,(1.12±0.35)cm2,(3.00±0.82)scores,(3.00±0.82)scores,(37.67±3.58)％.The postoperative intervertebral space height,dural sac area,low back pain VAS score,lower extremity pain VAS and ODI score of the patients in the RNRs positive group and the negative group were signifi-cantly improved compared with those before operation,and the differences were statistically significant(P＜0.05).There were statistically significant differences in the number of stenosed segments,preoperative intervertebral space height,dural sac area,low back pain VAS,lower extremity pain VAS,and ODI between the two groups(P＜0.05).There were significant differences in postoperative intervertebral space height and postoperative ODI between the two groups(P＜0.05),but there was no significant difference in intervertebral space height before and after operation and ODI score before and after operation(P＞0.05).There were significant differences in operation time,intraoperative blood loss,postoperative dural sac area,difference of dural sac area before and after operation,postoperative low back pain VAS,difference of low back pain VAS score before and after oper-ation,difference of lower extremity pain VAS before and after operation between the two groups(P＜0.05).Conclusion OLIF combined with posterior percutaneous internal fixation has a good effect on patients with or without RNRs.Multi-segmental lumbar spinal stenosis and decreased dural sac area may lead to the occurrence of RNRs,and LSS patients with RNRs have more severe symptoms.LSS patients with RNRs have worse surgical outcomes than those without RNRs.

Objective:To investigate the protective effect and possible mechanism of sulforaphane (SFN) on acute liver injury in mice induced by diquat (DQ) poisoning.Methods:Forty-eight male C57BL/6 mice were divided into Control group, DQ model group (DQ group), SFN intervention group (DQ+SFN group), and SFN control group (SFN group) using a random number table method, with 12 mice in each group. Acute liver injury mice model was established by one-time intraperitoneal injection of 1 mL of 40 mg/kg DQ solution at once. SFN group was injected with 1 mL of ddH 2O. After 4 hours of molding, 0.5 mL of 5 mg/kg SFN solution was injected into the peritoneal cavity of the DQ+SFN group and SFN group, once daily for 7 consecutive days. DQ group and Control group were injected with an equal amount of ddH 2O. Then, the mice were euthanized to collect liver tissue and blood samples, and the levels of plasma biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as oxidative stress indicators such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in liver tissue were measured. The changes of liver structure were observed under transmission electron microscopy. The apoptosis and reactive oxygen species (ROS) level in liver tissue were observed under fluorescence microscope. Western blotting was used to detect the protein expressions of nuclear factor E2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and cleaved caspase-9 in liver tissue. Results:Compared with the Control group, the liver mitochondria in the DQ group showed severe swelling, partial dissolution of the matrix, and cristae rupture and loss; the levels of plasma AST and ALT significantly increased, the MDA content in the liver increased, the activities of SOD and GSH decreased, the level of ROS significantly increased, the number of apoptotic cells in the liver significantly increased, the protein expressions of Nrf2 and HO-1 significantly decreased, and the protein expressions of Keap1 and cleaved caspase-9 significantly increased. Compared with the DQ group, the mitochondrial damage in the DQ+SFN group was reduced, the levels of plasma AST and ALT were significantly reduced [ALT (U/L): 58.22±4.39 vs. 79.94±3.32, AST (U/L): 177.64±8.40 vs. 219.62±11.60, both P < 0.01], the liver MDA content decreased, and the activities of SOD and GSH increased [MDA (μmol/g: 5.63±0.18 vs. 5.96±0.29, SOD (kU/g): 102.05±4.01 vs. 84.34±5.34, GSH (mmol/g): 16.32±1.40 vs. 13.12±1.84, all P < 0.05], the production of ROS in liver tissue was significantly reduced [ROS (fluorescence intensity): 115.90±10.89 vs. 190.70±10.16, P < 0.05], and apoptotic cells were significantly reduced (cell apoptosis index: 4.39±1.00 vs. 10.71±0.56, P < 0.01), the protein expressions of Nrf2 and HO-1 were significantly increased, while the protein expressions of Keap1 and cleaved caspase-9 were significantly decreased (Nrf2/β-actin: 1.15±0.04 vs. 0.93±0.05, HO-1/β-actin: 1.75±0.12 vs. 0.78±0.04, Keap1/β-actin: 1.00±0.14 vs. 1.28±0.13, cleaved caspase-9/β-actin: 1.31±0.12 vs. 1.81±0.09, all P < 0.05). However, there was no statistically significant difference in various indicators between the SFN group and the Control group. Conclusion:SFN can activate the Keap1/Nrf2 signaling pathway to alleviate DQ induced acute liver injury in mice.

Objective:To explore the effect of dietary modification-assisted multimodal therapy in the prevention and treatment of chronic prostatitis.Methods:A total of 132 cases of chronic prostatitis treated in the Outpatient Department of our hospital were randomly divided into an observation group(n=68)and a control group(n=64),the former following the Mediterranean dietary pattern,the latter adhering to their own dietary habits,and meanwhile both receiving lifestyle guidance,psychological counseling,symptomatic medication and physiotherapy according to their specific symptoms.The patients were followed up for 4 weeks,therapeutic effects were observed and comparisons were made between the two groups in the NIH-CPSI scores before and after treatment.Re-sults:Compared with the baseline,the quality of life(QOL)scores,pain and urination discomfort scores and total NIH-CPSI scores were significantly decreased in both the observation and the control groups after treatment(P<0.05),even more decreased in the former than in the latter,but with no statistically significant difference between the two(P>0.05).The rate of therapeutic effective-ness was higher in the observation group than in the control(87.1%vs 79.7%,but showed no statistically significant difference be-tween the two groups(P>0.05).Conclusion:Multimodal therapy is suitable for the management of different clinical manifesta-tions of individual patients,while dietary habits vary from person to person as well as from region to region.Therefore,scientific dietary modification for the prevention and treatment of CP/CPPS needs further exploration.

Objective:To investigate the selection of the modality of transperineal surgery and its effect in the treatment of pel-vic fracture-induced posterior urethral atresia(PUA).Methods:This study included 116 cases of PUA caused by pelvic fractures treated in our hospital from January 2012 to December 2021.We used transperineal resection of the urethral stricture and end-to-end u-rethral anastomosis(EEUA)as the first choice in the treatment of 79 cases.For the patients with the urethral atresia segment longer than 3 cm and evident urethral involution tension,we incised the penile septum,separated and removed the muscle tendon and scar tis-sue attached to the lower border of the pubis,and anastomosed with 4-0 absorbable thread for 8 stitches.For the other 37 cases for which we were not sure of effective suture of the membrane due to obvious scarring of the proximal urethra,the remaining urethra shor-ter than 5 mm or incomplete urethral mucosa,we selected conventional urethral pull-through operation(UPTO).We followed up the patients for 3-24 months postoperatively.Results:The total success rate of surgery was 78.4％(91/116),81.1％(30/37)in the UPTO and 77.2％(61/79)in the EEUA group,significantly higher in the former than in the latter(P=0.05).The rate of post-operative dysuria was remarkably lower in the UPTO than in the EEUA group(13.5％[5/37]vs 16.5％[13/79],P=0.05),and so was that of surgical failure(5.4％[2/37]vs 6.3％[5/79],P=0.05).The main causes of postoperative dysuria in the EEUA group included restenosis resulting from incomplete scar resection and the two sides of the anastomosed urethral segment not being at the coaxial level,while those in the UPTO group included the formation of mucosal flaps in the pulled-through urethra,and re-scarring leading to stricture or the pulled-through urethra not being at the coaxial level.Among the 7 cases of surgical failure due to recurrence,1 refused reoperation and opted for cystostomy tube drainage,and the other 6 underwent EEUA again 6 months later.Conclusion:EEUA is preferred as the first-choice surgery for PUA,while UPTO remains an effective treatment option in hospitals with preliminary skills and less experience in the management of PUA.

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