Objective:To analyze the clinical characteristics, treatments, and prognosis of patients with ovarian juvenile granulosa cell tumor (JGCT).Methods:Clinical and pathological data, and follow-up information of 34 patients diagnosed with JGCT from 2000 to 2021 were collected from the surveillance, epidemiology, and end results (SEER) database. A retrospective analysis was conducted to summarize the patients′ clinical and pathological characteristics, treatments, and prognosis. Propensity score matching (PSM) was used to match the JGCT cases with adult granulosa cell tumor (AGCT) cases in SEER database. A total of 96 patients with ovarian granulosa cell tumor (OGCT), including 32 cases of JGCT and 64 cases of AGCT, were enrolled in a matched cohort analysis. Univariate and multivariate Cox regression analysis were performed on the matched cohort to explore the risk factors for overall survival. Kaplan-Meier curves and the log-rank test were used to compare the survival outcomes between JGCT and AGCT.Results:(1) The median age at diagnosis for the 34 JGCT patients was 19.5 years (ranged: 1-48 years), with 3 patients aged ≤10 years, 16 patients aged 11-20 years, 11 patients aged 21-30 years, and 4 patients aged >30 years. Tumors originated unilaterally in 33 patients, with only 1 case originating bilaterally. The maximum tumor diameter was recorded in 26 patients, with a median size of 12.4 cm (ranged: 3.5-40.0 cm). According to the 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system, 19 patients were diagnosed with stage Ⅰ (including 10 cases with stage Ⅰa and 9 cases with stage Ⅰc), 4 patients with stage Ⅱ, 8 patients with stage Ⅲ, and 3 patients with stage Ⅳ. Two patients did not undergo surgery for the resection of lesions. Stage Ⅰ patients (15/19) underwent fertility-sparing surgery, while stage Ⅱ-Ⅲ patients underwent either fertility-sparing surgery or cytoreductive surgery (6 cases each). Stage Ⅳ patients underwent cytoreductive surgery (2 cases). Lymph node dissection was performed in 10 patients, among which only 1 patient with positive lymph nodes metastasis. None of the 34 patients received radiotherapy, while 18 patients received adjuvant chemotherapy (included neoadjuvant chemotherapy and postoperative adjuvant chemotherapy). The proportion of stage Ⅰ patients receiving adjuvant chemotherapy was relatively low, with only 4 out of 19 patients (including 2 out of 10 cases for stage Ⅰa and 2 out of 9 cases for stage Ⅰc). The proportions of patients receiving adjuvant chemotherapy for stages Ⅱ, Ⅲ and Ⅳ were 3 out of 4 cases, 8 out of 8 cases, and 3 out of 3 cases, respectively. The follow-up ended in December 2021, with 20 patients alive and 14 dead. The survival rate for ovarian JGCT patients was 59% (20/34). Among them, the survival rate for stage Ⅰ patients was 16/19, while for stage Ⅱ-Ⅳ patients, it was 4/15; there was a statistically significant difference ( P=0.002). Among stage Ⅱ-Ⅲ patients, the survival rate at the end of follow-up was 1/6 for those who underwent fertility-sparing surgery, compared to 3/6 for those who underwent cytoreductive surgery ( P=0.546). (2) For the 96 OGCT patients after matching using the PSM method, 64 ovarian AGCT patients had 5 deaths and 59 survivors during the follow-up period, the survival rate was 92% (59/64) at the end of follow-up. In contrast, among the 32 ovarian JGCT patients, 13 died and 19 survived, resulting in a survival rate of 59% (19/32) at the end of follow-up, which was statistically significant difference for the AGCT group ( P<0.001). Univariate Cox analysis revealed that histology, extent of surgery, chemotherapy, postoperative tumor residual status, and stage all significantly affected the survival outcomes of OGCT patients (all P<0.05). Multivariate Cox analysis revealed that variables with significant statistical differences were histology and stage. The median survival time for JGCT patients was 126 months, while AGCT patients median survival time was not reached with a statistically significant between the two groups ( P<0.001). Conclusions:Ovarian JGCT predominantly occur in adolescents and young women. Lymph node metastasis is relatively rare, and treatment primarily involves surgery and adjuvant chemotherapy. Most ovarian JGCT patients are diagnosed at stage Ⅰ, with a favorable prognosis. Fertility-preserving surgery is recommended, involving salpingo-oophorectomy on the affected side plus comprehensive staging surgery, or a second surgery to achieve comprehensive staging. For stage Ⅱ-Ⅳ ovarian JGCT patients, the prognosis is relatively poor, and fertility-preserving surgery should be considered with caution. The prognosis of ovarian JGCT patients is worse than that of ovarian AGCT patients.

Objective:To investigate the application of pedicled or perforator flaps transfer in the stage Ⅰ tissue defect repair after vulvar cancer surgery.Methods:From January 2005 to December 2023, 20 patients with vulvar cancer who underwent extensive episiectomy or extended episiectomy±inguinal lymph node resection+vulvar defect flap transfer were collected in Huanxing Cancer Hospital of Chaoyang District and Cancer Hospital and Peking Union Medical College, Chinese Academy of Medical Sciences. The survival status, appearance structure, sexual function satisfaction, tumor recurrence, and survival were analyzed.Results:(1) The median age of the 20 patients was 59 years (ranged: 29-73 years). There were 14 patients with recurrence and 6 patients with initial treatment. Pathological types: 14 cases of squamous cell carcinoma, 4 cases of Paget′s disease, 1 case of malignant melanoma, 1 case of adenoid cystic carcinoma (salivary gland type carcinoma). (2) Among the 20 patients, 6 cases underwent extensive episiotomy and 14 underwent extended episiotomy (1 of them underwent extensive excision of inguinal masses). Simultaneous inguinal lymphadenectomy (or dissection) were performed in 11 cases, including 7 cases of bilateral inguinal lymph node resection (or dissection) and 4 cases of unilateral inguinal lymph node resection (or dissection). Flap source: pedicled flap in 12 cases, perforator flap in 8 cases. All the 20 patients were removed at 10-14 days after operation, and all of them survived with rosy skin color and good elasticity. Seventeen cases of transferred flaps healed at stage Ⅰ, 2 cases healed at about 6 weeks due to incision leakage, and 1 case healed at 6 weeks after incision infection debridement. Six months after the operation, 2 cases felt that the pubic mound was thick and swollen. The other 18 cases showed vulva fullness and elasticity, no displacement of urethral opening, no deviation of urethra during urination, no stenosis of vaginal opening, no vulvar scar pain. In addition to 1 unmarried 29-year-old patient and 6 patients over 65 years old who had no sexual life before and after surgery, the other 13 patients had normal sexual life after surgery. (3) The follow-up period were 6 to 100 months, and 9 cases (45%, 9/20) relapsed during the follow-up period. There were 5 deaths (25%, 5/20), who were due to recurrence of vulvar cancer. The 5-year survival rate of 20 patients was 75%, including 83% in 6 patients with initial treatment and 71% in 14 patients with recurrence and reoperation.Conclusions:The combination of flap transfer for episioplasty with vulvar cancer surgery does not affect the wound healing. Because the external structure of the vulva is repaired, it could effectively improve the local wound healing ability and improve the organ function, and has good clinical application value.

Objective:To analyze the clinical characteristics, treatments, and prognosis of patients with ovarian juvenile granulosa cell tumor (JGCT).Methods:Clinical and pathological data, and follow-up information of 34 patients diagnosed with JGCT from 2000 to 2021 were collected from the surveillance, epidemiology, and end results (SEER) database. A retrospective analysis was conducted to summarize the patients′ clinical and pathological characteristics, treatments, and prognosis. Propensity score matching (PSM) was used to match the JGCT cases with adult granulosa cell tumor (AGCT) cases in SEER database. A total of 96 patients with ovarian granulosa cell tumor (OGCT), including 32 cases of JGCT and 64 cases of AGCT, were enrolled in a matched cohort analysis. Univariate and multivariate Cox regression analysis were performed on the matched cohort to explore the risk factors for overall survival. Kaplan-Meier curves and the log-rank test were used to compare the survival outcomes between JGCT and AGCT.Results:(1) The median age at diagnosis for the 34 JGCT patients was 19.5 years (ranged: 1-48 years), with 3 patients aged ≤10 years, 16 patients aged 11-20 years, 11 patients aged 21-30 years, and 4 patients aged >30 years. Tumors originated unilaterally in 33 patients, with only 1 case originating bilaterally. The maximum tumor diameter was recorded in 26 patients, with a median size of 12.4 cm (ranged: 3.5-40.0 cm). According to the 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system, 19 patients were diagnosed with stage Ⅰ (including 10 cases with stage Ⅰa and 9 cases with stage Ⅰc), 4 patients with stage Ⅱ, 8 patients with stage Ⅲ, and 3 patients with stage Ⅳ. Two patients did not undergo surgery for the resection of lesions. Stage Ⅰ patients (15/19) underwent fertility-sparing surgery, while stage Ⅱ-Ⅲ patients underwent either fertility-sparing surgery or cytoreductive surgery (6 cases each). Stage Ⅳ patients underwent cytoreductive surgery (2 cases). Lymph node dissection was performed in 10 patients, among which only 1 patient with positive lymph nodes metastasis. None of the 34 patients received radiotherapy, while 18 patients received adjuvant chemotherapy (included neoadjuvant chemotherapy and postoperative adjuvant chemotherapy). The proportion of stage Ⅰ patients receiving adjuvant chemotherapy was relatively low, with only 4 out of 19 patients (including 2 out of 10 cases for stage Ⅰa and 2 out of 9 cases for stage Ⅰc). The proportions of patients receiving adjuvant chemotherapy for stages Ⅱ, Ⅲ and Ⅳ were 3 out of 4 cases, 8 out of 8 cases, and 3 out of 3 cases, respectively. The follow-up ended in December 2021, with 20 patients alive and 14 dead. The survival rate for ovarian JGCT patients was 59% (20/34). Among them, the survival rate for stage Ⅰ patients was 16/19, while for stage Ⅱ-Ⅳ patients, it was 4/15; there was a statistically significant difference ( P=0.002). Among stage Ⅱ-Ⅲ patients, the survival rate at the end of follow-up was 1/6 for those who underwent fertility-sparing surgery, compared to 3/6 for those who underwent cytoreductive surgery ( P=0.546). (2) For the 96 OGCT patients after matching using the PSM method, 64 ovarian AGCT patients had 5 deaths and 59 survivors during the follow-up period, the survival rate was 92% (59/64) at the end of follow-up. In contrast, among the 32 ovarian JGCT patients, 13 died and 19 survived, resulting in a survival rate of 59% (19/32) at the end of follow-up, which was statistically significant difference for the AGCT group ( P<0.001). Univariate Cox analysis revealed that histology, extent of surgery, chemotherapy, postoperative tumor residual status, and stage all significantly affected the survival outcomes of OGCT patients (all P<0.05). Multivariate Cox analysis revealed that variables with significant statistical differences were histology and stage. The median survival time for JGCT patients was 126 months, while AGCT patients median survival time was not reached with a statistically significant between the two groups ( P<0.001). Conclusions:Ovarian JGCT predominantly occur in adolescents and young women. Lymph node metastasis is relatively rare, and treatment primarily involves surgery and adjuvant chemotherapy. Most ovarian JGCT patients are diagnosed at stage Ⅰ, with a favorable prognosis. Fertility-preserving surgery is recommended, involving salpingo-oophorectomy on the affected side plus comprehensive staging surgery, or a second surgery to achieve comprehensive staging. For stage Ⅱ-Ⅳ ovarian JGCT patients, the prognosis is relatively poor, and fertility-preserving surgery should be considered with caution. The prognosis of ovarian JGCT patients is worse than that of ovarian AGCT patients.

Objective:To investigate the application of pedicled or perforator flaps transfer in the stage Ⅰ tissue defect repair after vulvar cancer surgery.Methods:From January 2005 to December 2023, 20 patients with vulvar cancer who underwent extensive episiectomy or extended episiectomy±inguinal lymph node resection+vulvar defect flap transfer were collected in Huanxing Cancer Hospital of Chaoyang District and Cancer Hospital and Peking Union Medical College, Chinese Academy of Medical Sciences. The survival status, appearance structure, sexual function satisfaction, tumor recurrence, and survival were analyzed.Results:(1) The median age of the 20 patients was 59 years (ranged: 29-73 years). There were 14 patients with recurrence and 6 patients with initial treatment. Pathological types: 14 cases of squamous cell carcinoma, 4 cases of Paget′s disease, 1 case of malignant melanoma, 1 case of adenoid cystic carcinoma (salivary gland type carcinoma). (2) Among the 20 patients, 6 cases underwent extensive episiotomy and 14 underwent extended episiotomy (1 of them underwent extensive excision of inguinal masses). Simultaneous inguinal lymphadenectomy (or dissection) were performed in 11 cases, including 7 cases of bilateral inguinal lymph node resection (or dissection) and 4 cases of unilateral inguinal lymph node resection (or dissection). Flap source: pedicled flap in 12 cases, perforator flap in 8 cases. All the 20 patients were removed at 10-14 days after operation, and all of them survived with rosy skin color and good elasticity. Seventeen cases of transferred flaps healed at stage Ⅰ, 2 cases healed at about 6 weeks due to incision leakage, and 1 case healed at 6 weeks after incision infection debridement. Six months after the operation, 2 cases felt that the pubic mound was thick and swollen. The other 18 cases showed vulva fullness and elasticity, no displacement of urethral opening, no deviation of urethra during urination, no stenosis of vaginal opening, no vulvar scar pain. In addition to 1 unmarried 29-year-old patient and 6 patients over 65 years old who had no sexual life before and after surgery, the other 13 patients had normal sexual life after surgery. (3) The follow-up period were 6 to 100 months, and 9 cases (45%, 9/20) relapsed during the follow-up period. There were 5 deaths (25%, 5/20), who were due to recurrence of vulvar cancer. The 5-year survival rate of 20 patients was 75%, including 83% in 6 patients with initial treatment and 71% in 14 patients with recurrence and reoperation.Conclusions:The combination of flap transfer for episioplasty with vulvar cancer surgery does not affect the wound healing. Because the external structure of the vulva is repaired, it could effectively improve the local wound healing ability and improve the organ function, and has good clinical application value.

OBJECTIVE To prepare and characterize curcumin nanomicelles （hereinafter referred to as Cur/mPEG-PBLA micelles）， and to evaluate the in vitro hepatoprotective activity against alcohol liver disease （ALD）. METHODS Cur/mPEG-PBLA micelles were prepared with the dialysis method using methoxy-poly（ethylene glycol）-poly（β-benzyl-L-aspartate） （mPEG-PLGA） as the carrier. The appearance and microscopic morphology of Cur/mPEG-PBLA micelles were observed， and particle size， polydispersity index， Zeta potential， encapsulation efficiency and drug loading content were all detected. The in vitro release， pH stability， thermal stability， dilution stability， storage stability， plasma stability tests， and hemolysis experiments were all performed. The cell model of ALD was established with anhydrous ethanol intervention using human liver cancer cells and normal liver cells as objects， Cur reference solution as reference， to evaluate in vitro preventive and ameliorative effects of Cur/mPEG- PBLA micelles on ALD. RESULTS The prepared Cur/mPEG-PBLA micelles exhibited a pale-yellow milky light， with a spherical shape and uniform distribution. The average particle size was about 140 nm， and the polydispersity index was less than 0.3. Zeta potential was （－8.15±0.05） mV； the encapsulation efficiency was （73.26±3.16）%， and the drug loading content was （4.87± 0.42）%. The cumulative release of Cur reference substance was close to 80% at 10 h； the cumulative release of Cur/mPEG-PBLA micelles at 8 h was 28.94% and only 48.25% at 48 h. pH stability and thermal stability of Cur/mPEG-PBLA micelles were better than those of Cur reference solution； Cur/mPEG-PBLA micelles showed good dilution stability， storage stability and plasma stability， and would not cause hemolysis. Cur reference solution and Cur/mPEG-PBLA micelles had varying degrees of in vitro preventive and ameliorative effects on ALD in two types of cells； after 48 h of application， the above effects of Cur/mPEG-PBLA micelles were significantly better than those of Cur reference solution at the same mass concentration （P＜0.05）. CONCLUSIONS Cur/mPEG-PBLA micelles can improve pH stability and thermal stability of Cur， delayits degradation rate， and have better in vitro hepatoprotective activity against ALD.

Humans ; Granuloma, Pyogenic/pathology* ; Hemangioma, Capillary

OBJECTIVES: Stably expressed transforming growth factor -beta 1(TGF-β1)MCs were obtained and the effects of centellaasiatica (CA) granule on the expressions of Smad 2/3, Smad 7 and collagen Ⅳ and the level of Smad 2/3 phosphorylation were observed. METHODS: Lipofectin method was used to transfect TGF-β1 vector into MC, and the stably expressed TGF-β1 cell lines were selected by G418. The cells were divided into three groups. Control group:normal MC + RPMI 1640 + 10% normal rat serum; TGF-β1 group:stably expressed TGF-β1 MC + RPMI 1640 + 10% normal rat serum; CA group:stably expressed TGF-β1 MC + RPMI 1640 + 10% rat serum containing high CA. The experiments were repeated for five times. The contents of TGF-β1 and collagen Ⅳ in the culture medium were detected with ELISA, the expressions of mRNA and protein of TGF-β1, Smad 2/3, Smad 7 and the level of Smad 2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The contents of TGF-β1 and collagen Ⅳ in the culture medium of stably-expressed TGF-β1 MC were increased significantly, and the CA could reverse the effects of TGF-β1. The expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation were increased significantly in TGF-β1 transfected MC, and CA could dramatically reduce the expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation. The high expression of TGF-β1 decreased the expression of Smad 7 mRNA and protein, and the CA could antagonize the effect of mRNA expression. CONCLUSIONS The MCs stably-expressed TGF-β1 can activate the TGF-β1/Smad signal pathway and increase the expression of collagen Ⅳ. CA can decrease the occurrence of diabetic nephropathy(DN) by reducing the production of collagen Ⅳ through inhibiting the TGF-β1/Smad signal pathway.
Animals ; Cells, Cultured ; Centella ; chemistry ; Collagen Type IV ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Mesangial Cells ; drug effects ; metabolism ; Rats ; Signal Transduction ; Smad Proteins ; metabolism ; Smad2 Protein ; metabolism ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVE: To investigate the effects of centella asiatica (CA) granule on the expression of transform growth factor-β(TGF-β) and related down-stream signals in rats with early diabetic nephropathy(DN) and to clarify the molecular mechanisms of CA molecular mechanism of on preventing and curing early diabetic kidney disease DN by studying the effects of centella asiatica on TGF-β expression and related down-stream signals. METHODS: Sixty male SD rats were divided into control group(=10) and DN model group(=50). The model rats were made a right nephrectomy. One week later, diabetic nephropathy was induced by intraperitoneal injection of streptocozin(30 mg/kg) for three consecutive days. High blood glucose level of Tail vein (fasting glucose ≥ 16.7 mmol/L) and high urinary protein level(total protein level in DN group was more than twice higher than the control group) were measured to confirm early DN in rats. In the sham operation group, the right renal capsule was damaged and the corresponding amount of saline was injected. The model rats were administrated by the means of intragastric administration. The DN model group were divided into DN group, DN+fosinopril group(1.6 mg/kg·d), DN+high CA group(16.8 mg/kg·d), DN+medium CA group(11.2 mg/kg·d) and DN+low CA group(5.6 mg/kg·d), and each group was intragastric administration one time every morning last for 16 weeks. The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3, Smad7 and the level of Smad2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3 and the level of Smad2/3 phosphorylation were significantly increased, the expressions of mRNA and protein of Smad7 were dramatically decreased. The fosinopril and high dosage CA could reverse the effects of DN. CONCLUSIONS CA plays an important role in preventing and curing DN through regulating the TGF-β/Smad signaling pathways.
Animals ; Centella ; chemistry ; Diabetes Mellitus, Experimental ; Diabetic Nephropathies ; chemically induced ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, Transforming Growth Factor-beta Type I ; metabolism ; Receptor, Transforming Growth Factor-beta Type II ; metabolism ; Signal Transduction ; Smad2 Protein ; metabolism ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

Objective To investigate the clinicopathological features,survival,and the impact of postoperative adjuvant radiotherapy on the ovarian function in patients less than or equal to 35 years of age with stage ⅠB-ⅡA cervical cancer.Methods One hundred and eighty-six patients who were admitted to our hospital from 2000 to 2011 were retrospectively analyzed.An equal number of patients older than 35 years of age with cervical cancer within the same period were used as stage-marched controls.The Kaplan-Meier method was used to calculate the survival rates,and the log-rank test was used for pairwise comparison and univariate prognostic analyses.The Cox proportional hazards model was used for multivariate prognostic analyses.Results The patients less than or equal to 35 years of age had a significantly higher incidence of non-squamous carcinoma but significantly lower incidence rates of deep stromal invasion and lymph-vascular space invasion (LVSI) compared with the control group (P =0.000;P =0.008;P =0.000).Though young patients had significantly higher 5-year disease-free survival (DFS) and overall survival (OS) rates than the control group (93.7％ vs.84.5％,P=0.005;96.1％ vs.89.5％,P=0.033),age was not an independent prognostic factor (P =0.202;P =0.950).Among patients less than or equal to 35 years of age,lymph node metastasis and LVSI were independent prognostic factors for DFS (P =0.000;P =0.000),while LVSI and initial tumor size were independent prognostic factors for OS (P =0.000;P =0.000).There was no significant difference in the incidence of normal ovarian function between young patients treated with and without adjuvant radiotherapy after ovarian transposition (63％ vs.73％,P =0.422).Conclusions Patients less than or equal to 35 years of age with stage ⅠB-ⅡA cervical cancer have a better prognosis than the control group.However,age is not an independent prognostic factor.Postoperative adjuvant radiotherapy will not impair the function of transposed ovaries.

Objective:To approach the clinicopathologic characteristics, treatment modalities, and prognosis of the patients with double primary carcinoma of endometrial carcinoma and colorectal carcinoma and analyze the relationship between this disease and Lynch syndrome. Methods:The clinicopathologic and follow-up data of 34 cases with double primary carcinoma of endometrial carci-noma and colorectal carcinoma treated in Cancer Hospital of Chinese Academy of Medical Sciences were reviewed. Results:The medi-an age of the 34 patients was 51.5 years old (ranging from 39 to 76). Twenty-two of the total cases (22/34, 64.7%) had tumor family his-tory. The pathologic results indicated that 79.4%(27/34) was endometrioid adenocarcinoma. In the 34 cases, 33 were treated by surgical procedure. Of the 33 cases undergoing surgery, 17 patients with endometrial carcinoma and 19 with colorectal carcinoma received fur-ther adjuvant treatment of chemotherapy and/or radiotherapy. The 2-and 5-year survival rates were 84.3%and 63.1%in the 34 cases, respectively. Conclusion:The age of onset is earlier in the patients with double primary carcinoma than in those with sporadic colorec-tal carcinoma. Some cases have cancer family history, and their survival rates are similar to those of the patients with sporadic colorec-tum carcinoma. Diagnosis of some patients with double primary carcinoma may be in line with Lynch syndrome.