Objective To optimize the extraction process of Xuetong capsules and establish its quality control method. Methods The extraction process was optimized by orthogonal experiment using ethanol reflux method to investigate the effects of different factors on diphenylstilbene, aloin and extraction yield. The content of 5 anthraquinone compounds in Xuetong capsule was determined by HPLC. Results The optimal extraction process was to add 10 times ethanol, with an ethanol concentration of 70%, and extract 3 times, each time for 1 h; 5 components had a good linear relationship with peak area within a certain concentration range, r>0.999 7; The range of sample recovery rate was 93.66%-96.85%, RSD range of 1.48%-1.66%. The content determination results of the 5 components in three batches of Xuetong capsules were （0.632-0.641）, （0.660-0.681）, （1.968-1.991）, （2.547-2.580）, and （1.076-1.101） mg/g. Conclusion The method was accurate, reproducible, and highly feasible, which could be references for producing and improving the quality control standards of Xuetong capsules.

【Objective】 To explore the effectiveness and safety of different salvage therapies for local recurrence of tumor following primary prostate cryoablation so as to provide the reference for the treatment of prostate similar cases. 【Methods】 The clinical data of patients with prostate cancer (cT1c-4N0M0) who received salvage therapy for local recurrence of tumor following primary prostate cryoablation in the Sun Yat-Sen University Cancer Center during June 2014 and Dec. 2020 were retrospectively analyzed. Salvage therapies included local therapy (salvage radiotherapy, salvage cryoablation or salvage radical prostatectomy) and androgen deprivation therapy (ADT). 【Results】 Altogether 8 patients were involved. The median age was 71(63-76) years, the median prostate specific antigen (PSA) at the first diagnosis was 17.650(10.380-325.100) ng/mL, the median nadir post-cryoablation PSA was 0.041(0.003-0.541) ng/mL, and the median PSA at local recurrence was 3.030(2.090-19.180) ng/mL. Abnormal digital rectal examination was found in 3 cases, and radiographic evidence of local recurrence was found in 7 cases. Prostate biopsy was performed in 4 cases, 2 of which had positive results. The median follow-up after salvage therapy lasted for 54 (9-75) months. Four cases received salvage radiotherapy, 2 of which developed bloody stool, hematuresis and urinary tract infection, and recovered after conservative treatment; 1 case received salvage cryoablation without side effects; 1 case underwent radical prostatectomy and radiotherapy, developed lymphorrhagia and recovered after conservative treatment; 2 cases received ADT alone, one experienced hot flashes and recovered after conservative treatment, and the other progressed into castration-resistant prostate cancer after 63 months. No other progression or death occurred at the termination of follow-up. 【Conclusion】 Salvase therapy (salvage radiotherapy, salvage cryoablation, salvage radical prostatectomy) and ADT can be used for local recurrence of tumor following primary prostate cryoablation. However, large-scale prospective research is needed to confirm the effectiveness and safety of different therapies.

Objective To develop a high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for simultaneous determination of five flavonoids in Ganmao'an granules(GMA).Methods Chromatographic separation was achieved on a Kromasil C18 Column(150 mm×4.6 mm,5 μm,100 ?),which was eluted with methanol(A)-0.1％formic acid(B)at the flow rate of 1.0 ml/min.The gradient condition was as follows:0-20 min,35％A,and 20-40 min,45％A.The column temperature was 25 ℃.Analytes were detected using a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source in the negative ion scanning.The multiple reaction monitoring mode was used for qualitative analysis.For each flavonoid,two precursor ion/product ion transitions were chosen:lutin m/z 609.1→300.1,hyperin and isoquercitrin m/z 463.0→300.1,quercetin m/z 301.0→151.0,luteolin m/z 285.0→132.9.Results Five flavonoids showed the good relationships within their own concentration ranges(correlation coefficient r>0.999 1),whose average recoveries were in the range of 100.63％-102.81％with RSDs of 0.67％-2.07％.The content results of rutin,hyperoside,isoquercetin,quercetin,and luteolin in 10 batches of GMA were 32.23-479.83,0.291-1.825,11.44-20.54,6.32-18.41,3.46-6.51 μg/g,respectively.Conclusion The results indicated that the developed method was sensitive,accurate and could provide excellent specificity for simultaneous determination of five flavonoids in GMA.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Nowadays the contents and form of community pharmaceutical services have become more complex, it is necessary to develop pharmaceutical services in line with the characteristics of community and meeting the actual needs of patients. The "dual drug" refers the combination of pharmaceutical effects of the drug with the language effects of pharmacists. This paper reviews the status quo of pharmaceutical services at home and abroad, patient needs and demands, problems and challenges in pharmaceutical services. The article introduces the experiences of development and implementation of pharmaceutical services based on the"dual drug"priciple, and the preliminary results in author′s institution, to provide reference for a nevel model of pharmaceutical services.

Objective To explore the pharmacokinetic properties of curcumin nano emulsion and its pharmacodynamic effects on hyperlipidemia in rats. Methods The method for determination of curcumin was established by HPLC-MS. The pharmacokinetics characteristics of curcumin nano emulsion oral administration system were investigated. SD rats were used as model animals to establish hyperlipidemia animal models, and the pharmacodynamic effects of curcumin nano emulsion on hyperlipidemia induced by high fat diet was preliminarily investigated. Results The results of pharmacokinetic studies in vivo showed that the relative bioavailability of curcumin nano emulsion was 313.47% with bulk drug group as the reference preparation. The relative bioavailability of curcumin nano emulsion was 279.52 % with tablets as reference preparation. C_max of curcumin nano emulsion group was 201.48 % of that of bulk drug group and 193.02 % of that of tablet group, and had higher MRT value (183.52 % of that of bulk drug group and 154.21 % of that of tablet group) than bulk drug group and tablet group. Pharmacodynamics research results showed that curcumin nano emulsion oral administration system could significantly reduce the levels of triglyceride and LDL-c in serum of model rats, and relieve liver lipid deposition and liver injury caused by high-fat diet in model animals. Conclusion The oral administration system of curcumin nano emulsion could effectively improve the bioavailability of curcumin, which has a good hypolipidemic effect. It also could control the weight gain of hyperlipidemia rats and improve the changes of liver coefficient caused by lipid metabolism disorder.

Objective:To evaluate the efficacy of first-line tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors (ICI) in metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC).Methods:The data of 87 metastatic FH-deficient RCC patients from West China Hospital ( n=44), Renji Hospital ( n=27) and Sun Yat-sen University Cancer Center (n=16) from Mar 2019 to Aug 2022 were retrospectively analyzed. The median age was 37(30, 47) years, the male to female ratio was 1.9∶1. The median size of tumor was 7.5(5.0, 10.0) cm. Sixty-one patients (70.1%) had germline FH mutations, and 26 patients (29.9%) had somatic FH mutations. Forty-nine patients (56.3%) metastasis disease at initial diagnosis, and 38 patients (43.7%) had metachronous metastasis. The most common site of metastasis was lymph node (41/87, 47.1%), followed by bone (33/87, 37.9%), liver (22/87, 25.3%), and lung (14/87, 16.1%). Fifteen patients (17.2%) had weak expression of FH protein and 59 patients (67.8%) had positive PD-L1 expression. The most common treatments were sintilimab plus axitinib (52/87, 59.8%), followed by pembrolizumab plus cabozantinib (7/87, 8.0%), tirelizumab plus axitinib (6/87, 6.9%), pembrolizumab plus axitinib (5/87, 5.7%), and toripalimab plus axitinib (4/87, 4.6%). Thirteen patients (13/87, 14.9%) received other ICI plus TKI combination treatments. Statistical analysis was conducted using R 4.2.3 software. Kaplan Meier survival curve was used to evaluate survival data, and log-rank test was used to compare differences between treatment groups. Results:The overall objective response rate (ORR) and disease control rate (DCR) of first-line TKI + ICI were 39.1% and 89.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 16.5 months and 71.0 months, respectively. For first-line sintilimab plus axitinib, the ORR and DCR were 44.2% and 92.3%, respectively. The median PFS was 17.3 months and the median OS was not reached for this combination treatment. The efficacy of first-line tirelizumab plus axitinib was inferior to other treatment strategies (median PFS: 4.0 vs. 16.6 months, P<0.001; median OS: 22.0 vs. 71.0 months, P=0.043). Subgroup analyses further showed that the efficacy of ICI+ TKI combination therapy was consistent in patients with different clinicopathologic and genomic features. However, patients with liver metastasis had shorter OS than those without liver metastasis (median OS: 26.3 vs. 71.0 months, P=0.021). Conclusion:First-line TKI + ICI is effective for metastatic FH-deficient RCC and can significantly prolong the survival of the patients.

Objective To establish the HPLC method of assay for diphenhydramine hydrochloride in compound diphenhydramine cream. Method HPLC analysis was carried on ACE5C₁₈S/N-A66766 column (150 mm×4.6 mm, 5 µm) with the mobile phase of methanol-water-triethylamine (70:30:0.67, adjusting pH to 6.50 with phosphoric acid) at room temperature. The detection wavelength was set at 230 nm and the flow rate was 1.0 ml/min. The analyte was extracted from the cream and 20 μl of sample was injected. Results The calibration curve of diphenhydramine hydrochloride was linear in the range of 39.52-197.6 µg/ml (r=0.999 7). The average recovery of diphenhydramine hydrochloride was 100.5% (RSD=1.25%, n=9). The repeatability of the method was expressed using RSD with 0.78% (n=6). The results of assay were 101.3%, 99.83% and 99.62%. Conclusion The method is accurate, sensitive, selective and repeatable, which can be applied for improving the quality standard of compound diphenhydramine cream.

Prostate cancer is one of the most common cancers threatening the health of males. The incidence of prostate cancer in China is on the rise. Non-metastatic castration-resistant stage is a special disease stage during the progression of prostate cancer, early identification of nmCRPC and prompt intervention can help delay disease progression and prolong patient survival. In recent years, many studies demonstrated the efficacy of novel androgen receptor inhibitors such as apalutamide, in prolonging metastasis-free survival and time to symptomatic progression in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). This article reviews the recent progress of novel androgen receptor inhibitors for nmCRPC.

Objective To investigate the risk factors predicting pathology grade upgrading after radical prostatectomy using the 2014 International Society of Urologic Pathology (ISUP) grading system.Methods A total of 205 patients who underwent biopsy and radical prostatectomy from January 2017 to December 2018 were reviewed retrospectively.The median and range of the patients' age,PSA level,prostate volume,number of biopsy core examined,Gleason score and ISUP grade were 66 (45-81) years old,17.16(0.89-1254.00)ng/ml,36.4(4.1-152.1) rnl,10(1-15),7(6-10),and 3(1-5) respectively.The patients were divided into group of upgrading ISUP grade and group without upgrading ISUP grade.Multivariate Logistic regression analysis and receiving operating characteristic curve analysis were performed to identify predictors of ISUP upgrading and determine the optimal cut off value respectively.Result The median and range of Gleason score and ISUP grade after radical prostatectomy were 7 (6-10),and 3 (1-5) respectively.The radical prostatectomy ISUP grade upgraded in 73 (35.6％) out of 205 cases when compared with biopsy ISUP grade.Radical prostatectomy ISUP grades were concordant in 91 cases (44.4％) and downgraded in 41 cases(20.0％).Of 101 with biopsy ISUP grades less than or equal to 2,the ISUP grade of radical prostatectomy upgraded in 58 cases (57.4％),while radical prostatectomy ISUP grade upgraded in only 18 (26.9％) of 67 patients with biopsy ISUP grades of 3 or 4.Biopsy ISUP grades represent an independent predictor for ISUP grade upgrading after radical prostatectomy (OR =0.496,P ＜ 0.001).Conclusion Patients with biopsy ISUP grades less than or equal to 2 are at great risk of ISUP grade upgrading after radical prostatectomy.