To systematically synthesize evidence on multiple KRAS G12C inhibitors(KRAS G12C inhibitors, KRAS G12Ci) as monotherapy within a unified population and recommended-dose framework, establish a comparable benchmark range of efficacy and safety for previously treated patients with advanced or metastatic KRAS G12C-mutant non-small cell lung cancer(NSCLC), and explore potential effect modifiers.

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.

ObjectiveTo analyze the epidemiological characteristics of newly diagnosed occupational welder's pneumoconiosis (OWP) in the shipbuilding industry in Guangzhou City from 2006 to 2022. Methods Data on newly diagnosed OWP cases in the shipbuilding industry in Guangzhou City from 2006 to 2022 was collected and ananlyzed from the Health Hazard Monitoring Information System subsystem of the Chinese Disease Prevention and Control System. ResultA total of 250 cases of new welder's pneumoconiosis were diagnosed in the shipbuilding industry in Guangzhou City from 2006 to 2022. The number of new cases per year showed an initial increase followed by a rapid decline, reaching a peak in 2013 (65 cases). Most of the cases were male, accounted for 99.2%. There were 220 cases reported the OWP stage, with the stage Ⅰ and stage Ⅱ cases accounted for 93.6% and 6.4%, respectively, but no stage Ⅲ cases were reported. The median (M) age and the 25th and 75th percentiles (P₂₅, P₇₅) at diagnosis was 43.0 (39.0, 47.0) years and the dust exposure years M (P₂₅, P₇₅) was 11.2 (8.1, 14.7) years. The M of age at diagnosis of new OWP cases in 2015-2018 and 2019-2022 were higher than those in 2006-2010 and 2011-2014, respectively (all P<0.05). The M of dust exposure duration of new OWP cases from 2006-2010 and 2019-2022 was higher than that in cases from 2015-2018 and 2011-2014, respectively (all P<0.05). Most of the small shadows of the cases were circular small p shadows and distributed in the bilateral middle and lower lung zones, with a density mostly of 1/1, according to the X-ray chest films. Conclusion The hazard of welding fumes in the shipbuilding industry in Guangzhou City has been controlled, but the prevention and control of OWP among welders remains severe.

【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 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 investigate the prognosis after salvage radiotherapy with or without hormone therapy for prostate cancer.Methods:From May 2014 to December 2020, 248 patients undergoing salvage radiotherapy due to prostate-specific antigen (PSA)persistence or biochemical progression after radical prostatectomy at Sun Yat-sen University Cancer Center (n=157) and West China Hospital, Sichuan University (n=91) were analyzed. Median age was 66 (45-78) years old. Median PSA was 23.50 (0.18-845.00) ng/ml. The number of PSA persistence and biochemical progression were 143 (59%) and 105 (42%). The number of pT 2, pT 3a, pT 3b, pT 4, and unknown T stage was 99, 49, 78, 15 and 7 cases.The number of N 0, N 1 and unknown N stage was 153, 44 and 51 cases. 165 cases had positive surgical margin. Gleason score of 6, 7, 8, >8 score and unknown was in 12, 104, 34, 90 and 8 patients. Early and late salvage radiotherapy was performed in 117 and 131 patients, and 70 patients (28%) were CRPC. Hormone therapy was used combined with radiotherapy in 182 patients (73%). PSA decline after radiotherapy was compared with Chi-squre test. Kaplan-Meier method and log-rank test were used to compare progression free-survival (PFS)after radiotherapy. Univariate and multivariate analyses of PFS were performed using Cox proportional hazards model. Early salvage radiotherapy was defined as PSA≤0.5 ng/ml before radiotherapy, and late salvage radiotherapy was defined as PSA>0.5ng/ml. Results:PSA response (PSA decline ≥50%) rate was 94% (233/248), and 82% (203/248) patients had PSA decline ≥ 90%. Twelve (5%) patients had rising PSA after completing radiotherapy, but only 4 (2%) had real progression. The median PFS was 69 months (95% CI 68-70), and 3-year and 5-year PFS rate were 80% and 67%. PFS of PSA persistence and biochemical progression were similar ( HR =0.71, 95% CI 0.37-1.37, P=0.311). Compared with late salvage radiotherapy, early salvage radiotherapy had better PFS [69 (95% CI 68-70) vs. 59 (95% CI 44-74) months, P<0.001]. Compared with hormone sensitive, castration-resistant was associated with worse PFS (5-year PFS rate 74% vs. 51%, P<0.001). In multivariate analysis, Gleason score>8, castration-resistant and late salvage radiotherapy were unfavorable prognostic factors. Conclusions:In patients receiving salvage radiotherapy with or without hormone therapy for PSA persistence and biochemical progression after radical prostatectomy, high PSA level before radiotherapy and castration resistant is associated with poor prognosis.

Objective:To evaluate the efficacy and safety of switch from prednisone (AA+ P) to dexamethasone (AA+ D) in metastatic castration-resistant prostate cancer patients (mCRPC) progressing on abiraterone plus prednisone.Methods:Between November 2016 and December 2019, 46 mCRPC patients were switched to AA+ D after progression on AA+ P at Sun Yet-sen University Cancer center. Median age was 72 years(50 to 89 years), with median androgen deprivation therapy (ADT) duration 14.6 months(2.1 to 168.5 months). PSA level at the time of diagnosis, the initiation of AA+ P treatment, the time of switch were 258.9 ng/ml, 56.6 ng/ml, 25.1 ng/ml, respectively. 42 (91.3%), 12(26.1%), 7(15.2%) patients had bone metastasis, lymph node metastasis, visceral metastasis, respectively. 28 patients had Gleason score ≥8, and 11 patients had Gleason score<8. The primary endpoint was progression free-survival (PFS). Secondary endpoints included PSA response rate of PSA decline ≥50% and ≥30% and safety. Patients were divided into different risk level groups according to PSA level at the time of switch and PFS on AA+ P.Results:The median follow-up of 46 patients was 4.9 months, 40 patients progressed at the last follow-up, the treatment was terminated in 1 patient because of cerebral infarction, 5 patients were still on the treatment of AA+ D. Median PFS on AA+ D of 46 patients was 3.7 (1.6-24.1) months. A total of 12 (26.1%) patients showed a PSA decline≥50% after treatment with AA+ D, and 21 (45.7%) patients showed a PSA decline ≥30%. The median PFS was 8.5 (2.7-24.1) and 3.0 (1.6-17.8) months for patients with PSA decline≥50% and PSA didn’t decline ≥50%, respectively. Four factors below were significantly associated with a longer PFS on AA+ D after steroid switch in univariate analysis: lower PSA level at the time of switch (<30 ng/ml, HR=0.30, 95% CI 0.14-0.64, P=0.002), longer ADT sensitivity duration (≥18 months, HR=0.55, 95% CI 0.28-1.06, P=0.045), longer AA+ P treatment PFS (≥8 months, HR=0.36, 95% CI 0.18-0.72, P=0.004), and greater PSA decline on AA+ D (≥50%, HR=0.30, 95% CI 0.17-0.75, P=0.007). The above mentioned factors were also independent prognostic factors associated with better PFS on AA+ D after steroid switch in multivariate analysis. Treatment with AA+ D was well tolerated in all patients, with no grade 3/4 toxicity reported. Conclusions:Switching from prednisone to dexamethasone is effective and safe in mCRPC patients progressing on abiraterone plus prednisone. Patients with lower PSA level at the time of switch, longer ADT sensitivity duration, longer AA+ P treatment PFS and greater PSA decline on AA+ D might gain better efficacy.

Objective: To explore the postoperative effect, prognosis, and prognostic factors for benign testicular tumors. Methods: We retrospectively analyzed the clinical data of 35 patients with benign testicular tumors between May 2004 and May 2017 from Sun Yat-sen University Cancer Center, and the patients were followed up until October 2017. Results: The mean age of the 35 patients was 18.8 (0.4-44.0) years. Among them, 14 patients (40.0%) underwent testis-sparing surgery and 21 (60.0%) underwent radical orchiecto-my, and the tumor sizes were 1.8 (0.4-4.0) cm and 2.7 (1.0-8.0) cm, respectively. All patients had been cured without obvious perioper-ative complications. Postoperative histopathological tumor types included 18 epidermal cysts, 10 mature teratomas, 4 interstitial cell tumors, and 3 adenomatoid tumors. Frozen section examination of 10 cases had been operated, and all results were consistent with paraffin pathology. No patient who underwent testis-sparing surgery showed recurrence and/or metastasis during follow-up, and their sexual function and fertility were well preserved. Conclusions: Testis-sparing surgery is reliable, and the size of the tumor determines its implementation. An intraoperative rapid frozen section examination should be performed in patients with testicular neoplasms of a benign or variable nature diagnosed before operation. Patients with benign testicular tumors should undergo testis-sparing surgery, whereas others should undergo radical orchiectomy.