Objective:To investigate the clinicopathological features including immunophenotype, molecular characteristics, differential diagnosis and prognosis of SMARCB1-deficient renal medullary carcinoma (RMC) without sickle cell trait.Methods:The clinicopathological data of 12 cases of SMARCB1-deficient RMC without sickle cell trait were collected from 7 domestic institutions during the period of 2015 to 2024. Their clinical characteristics, morphological features and immunohistochemical properties were observed and analyzed. High-throughput DNA-targeted next-generation sequencing was performed, and follow-up data were gathered along with relevant literature review.Results:Among the 12 patients, 5 were female and 7 were male. The patients age ranged from 27 to 84 years with a median age of 58.5 (46.0, 71.0) years. None of them had sickle cell disease or other hemoglobinopathies. Eight cases occurred in the left kidney and 4 cases were located in the right kidney. The average maximum diameter of the tumor was 6.1 (4.0,7.5) cm, with a range of 2.0 to 14.9 cm (the median maximum diameter 5.5 cm). Histologically, the tumors showed poorly differentiated adenocarcinoma, arranged in solid and tubular patterns. Papillary structure was noted in 5 cases, cribriform structure in 3 cases, rhabdoid differentiation in 3 cases, and sarcomatoid differentiation in 2 cases. Inflammatory desmoplastic stromal reaction was observed in 8 cases, among which stromal myxoid degeneration was seen in 6 cases. Tumor necrosis was apparent in 6 cases. The tumor cells had abundant eosinophilic or clear cytoplasm and prominent nucleoli. The nuclear grading was grade 3 or 4 according to the International Society of Urological Pathology (ISUP). Immunohistochemical staining showed that the tumor cells of all 12 cases expressed PAX8 and loss of SMARCB1/INI1 protein expression, and 5 of 10 cases expressed OCT3/4. Seven samples had valid archived paraffin tissues for high-throughput DNA-targeted next-generation sequencing. The results showed that all 7 cases had pathogenic mutations in the SMARCB1 gene. The mutation sites included exon5 c.595A>T (p.K199*), exon2 c.200_207del (p.S67*), exon2 p.G69VfsTer16, exon7 c.986G>T (p.S329I), exon7 c.886A>T (p.K296*), exon6 c.635T>A (p.L212*), exon5 c.577del (p.M193Wfs16), and exon6 c.784del (p.V262Sfs5). Follow-up data were obtained for 6 of 12 patients. Among them, 1 patient had lung and bone metastases, 1 patient had liver and bone metastases and 1 patient had multiple bone metastases at the time of diagnosis; 1 patient had bone metastases 5 months after surgery. One patient died of postoperative complications 10 days after surgery, 4 patients died of tumors (the survival time ranged from 4 to 8 months), and 1 patient had no recurrence or metastasis during the 8-month follow-up after surgery.Conclusions:SMARCB1-deficient RMC without sickle cell trait is a highly aggressive and poorly differentiated renal cell carcinoma. It has similar histomorphology, immunophenotype, molecular characteristics and prognosis to RMC, which further supports that it is a sporadic subtype of RMC related to sickle cell trait.

Objective:To investigate the clinicopathological features including immunophenotype, molecular characteristics, differential diagnosis and prognosis of SMARCB1-deficient renal medullary carcinoma (RMC) without sickle cell trait.Methods:The clinicopathological data of 12 cases of SMARCB1-deficient RMC without sickle cell trait were collected from 7 domestic institutions during the period of 2015 to 2024. Their clinical characteristics, morphological features and immunohistochemical properties were observed and analyzed. High-throughput DNA-targeted next-generation sequencing was performed, and follow-up data were gathered along with relevant literature review.Results:Among the 12 patients, 5 were female and 7 were male. The patients age ranged from 27 to 84 years with a median age of 58.5 (46.0, 71.0) years. None of them had sickle cell disease or other hemoglobinopathies. Eight cases occurred in the left kidney and 4 cases were located in the right kidney. The average maximum diameter of the tumor was 6.1 (4.0,7.5) cm, with a range of 2.0 to 14.9 cm (the median maximum diameter 5.5 cm). Histologically, the tumors showed poorly differentiated adenocarcinoma, arranged in solid and tubular patterns. Papillary structure was noted in 5 cases, cribriform structure in 3 cases, rhabdoid differentiation in 3 cases, and sarcomatoid differentiation in 2 cases. Inflammatory desmoplastic stromal reaction was observed in 8 cases, among which stromal myxoid degeneration was seen in 6 cases. Tumor necrosis was apparent in 6 cases. The tumor cells had abundant eosinophilic or clear cytoplasm and prominent nucleoli. The nuclear grading was grade 3 or 4 according to the International Society of Urological Pathology (ISUP). Immunohistochemical staining showed that the tumor cells of all 12 cases expressed PAX8 and loss of SMARCB1/INI1 protein expression, and 5 of 10 cases expressed OCT3/4. Seven samples had valid archived paraffin tissues for high-throughput DNA-targeted next-generation sequencing. The results showed that all 7 cases had pathogenic mutations in the SMARCB1 gene. The mutation sites included exon5 c.595A>T (p.K199*), exon2 c.200_207del (p.S67*), exon2 p.G69VfsTer16, exon7 c.986G>T (p.S329I), exon7 c.886A>T (p.K296*), exon6 c.635T>A (p.L212*), exon5 c.577del (p.M193Wfs16), and exon6 c.784del (p.V262Sfs5). Follow-up data were obtained for 6 of 12 patients. Among them, 1 patient had lung and bone metastases, 1 patient had liver and bone metastases and 1 patient had multiple bone metastases at the time of diagnosis; 1 patient had bone metastases 5 months after surgery. One patient died of postoperative complications 10 days after surgery, 4 patients died of tumors (the survival time ranged from 4 to 8 months), and 1 patient had no recurrence or metastasis during the 8-month follow-up after surgery.Conclusions:SMARCB1-deficient RMC without sickle cell trait is a highly aggressive and poorly differentiated renal cell carcinoma. It has similar histomorphology, immunophenotype, molecular characteristics and prognosis to RMC, which further supports that it is a sporadic subtype of RMC related to sickle cell trait.

Objective:To observe the ameliorative effects of exogenous miR-146a-5p on lipopolysaccharide (LPS)-induced embryonic resorption and fetal mouse dysplasiamice, and to preliminarily investigate its mechanism of action.Methods:1) After 36 healthy adult female mice were mated with male mice, uterine tissues were collected from females on day (D) 0 (D0/not pregnant), D0.5 (the day of embryo observed), D4.5, D7.5, D9.5 and D13.5 of gestation, and the expression levels of miR-146a-5p and its target gene TRAF6 protein in uterine tissues of mice at different gestation periods were detected by real-time fluorescent quantitative PCR (qPCR) and Western blotting. 2) The mice on D7.5 of pregnancy were treated with intraperitoneal injection of saline (control, COL group), intraperitoneal injection of 250 μg/kg LPS (named LPS250 group), LPS combined with tail vein injection of 10 nmol miR-146a-5p unrelated sequence (negative control, NC, named LPS250+NC group), or LPS combined with tail vein injection of 10 nmol miR-146a-5p agonist (miR-146a-5p agomir, named LPS250+miR-146a-5p agomir group). The total number of embryos and the number of absorbed embryos in the uterus of pregnant mice were measured and statistically analyzed on D8.5, and the expression levels of TNFα mRNA and TRAF6 protein in uterine tissues were detected by qPCR and Western blotting. 3) Then we reduced the dosage of LPS to 50 μg/kg and treated the same groups, named LPS50+NC group, LPS50+miR-146a-5p agomir group, respectively. The total number of fetal mice/embryos, the number of absorbed embryos, the number of surviving fetal mice, the weight of surviving fetal mice and the weight of the placenta were measured and statistically analyzed on D16.5. 4) Primary mouse bone marrow-derived macrophages (BMDM) were isolated and cultured. Mouse BMDM was inducted to M1 polarization by LPS stimulation, and then was transient transfected miR-146a-5p mimics or their NC fragments. The expression levels of TNFα mRNA and pSTAT1 protein were detected by qPCR and Western blotting. Results:The expression level of miR-146a-5p was significantly higher in the implantation sites of D7.5, D9.5 and D13.5 pregnant mice than in the non-implantation sites ( P=0.013, P=0.012, P=0.003), and the protein expression level of TRAF6 was significantly lower in the implantation site of D13.5 pregnant mice than in the non-implantation site ( P=0.012). After intraperitoneal injection of 250 μg/kg of LPS into D7.5 pregnant mice, the embryo absorption rate of the LPS group on D8.5 was 43.13%±3.31%, which was significantly higher than that of COL group (0%, P=0.002), while the embryo absorption rate of the LPS250+miR-146a-5p agomir group (13.50%±0.87%) was significantly lower than that of the LPS250+NC group (59.33%±4.04%, P=0.001). After intraperitoneal injection of 50 μg/kg of LPS combined with tail vein injection of NC or miR-146a-5p agomir to D7.5 pregnant mice, the fetal mouse weight [(0.29±0.09) g] and placental weight [(0.06±0.02) g] of surviving fetal mice in the LPS50+NC group on D16.5 and the LPS50+miR-146a-5p agomir group were statistically significant [(0.46±0.06) g, P<0.001; (0.07±0.02) g, P=0.021], and the differences in the number of absorbed embryos and embryo uptake rate between the two groups were not statistically significant (all P>0.05). The expression levels of both pSTAT1 protein and TNFα mRNA were significantly downregulated in BMDM transfected with miR-146a-5p mimics compared with those transfected with NC ( P=0.012, P=0.039). Conclusion:miR-146a-5p expression levels were significantly increased at the maternal-fetal interface during the late stage of mouse embryo implantation and placental development. Exogenous miR-146a-5p could effectively improve LPS-induced mouse embryo resorption and fetal mouse dysplasia. miR-146a-5p could inhibit the M1 polarization activity of mouse macrophages, suggesting that miR-146a-5p may inhibit the M1 polarization activity of mouse macrophages by suppressing M1 polarization of mouse maternal-fetal interface macrophages to safeguard the normal establishment and maintenance of pregnancy.

Objective:To observe the ameliorative effects of exogenous miR-146a-5p on lipopolysaccharide (LPS)-induced embryonic resorption and fetal mouse dysplasiamice, and to preliminarily investigate its mechanism of action.Methods:1) After 36 healthy adult female mice were mated with male mice, uterine tissues were collected from females on day (D) 0 (D0/not pregnant), D0.5 (the day of embryo observed), D4.5, D7.5, D9.5 and D13.5 of gestation, and the expression levels of miR-146a-5p and its target gene TRAF6 protein in uterine tissues of mice at different gestation periods were detected by real-time fluorescent quantitative PCR (qPCR) and Western blotting. 2) The mice on D7.5 of pregnancy were treated with intraperitoneal injection of saline (control, COL group), intraperitoneal injection of 250 μg/kg LPS (named LPS250 group), LPS combined with tail vein injection of 10 nmol miR-146a-5p unrelated sequence (negative control, NC, named LPS250+NC group), or LPS combined with tail vein injection of 10 nmol miR-146a-5p agonist (miR-146a-5p agomir, named LPS250+miR-146a-5p agomir group). The total number of embryos and the number of absorbed embryos in the uterus of pregnant mice were measured and statistically analyzed on D8.5, and the expression levels of TNFα mRNA and TRAF6 protein in uterine tissues were detected by qPCR and Western blotting. 3) Then we reduced the dosage of LPS to 50 μg/kg and treated the same groups, named LPS50+NC group, LPS50+miR-146a-5p agomir group, respectively. The total number of fetal mice/embryos, the number of absorbed embryos, the number of surviving fetal mice, the weight of surviving fetal mice and the weight of the placenta were measured and statistically analyzed on D16.5. 4) Primary mouse bone marrow-derived macrophages (BMDM) were isolated and cultured. Mouse BMDM was inducted to M1 polarization by LPS stimulation, and then was transient transfected miR-146a-5p mimics or their NC fragments. The expression levels of TNFα mRNA and pSTAT1 protein were detected by qPCR and Western blotting. Results:The expression level of miR-146a-5p was significantly higher in the implantation sites of D7.5, D9.5 and D13.5 pregnant mice than in the non-implantation sites ( P=0.013, P=0.012, P=0.003), and the protein expression level of TRAF6 was significantly lower in the implantation site of D13.5 pregnant mice than in the non-implantation site ( P=0.012). After intraperitoneal injection of 250 μg/kg of LPS into D7.5 pregnant mice, the embryo absorption rate of the LPS group on D8.5 was 43.13%±3.31%, which was significantly higher than that of COL group (0%, P=0.002), while the embryo absorption rate of the LPS250+miR-146a-5p agomir group (13.50%±0.87%) was significantly lower than that of the LPS250+NC group (59.33%±4.04%, P=0.001). After intraperitoneal injection of 50 μg/kg of LPS combined with tail vein injection of NC or miR-146a-5p agomir to D7.5 pregnant mice, the fetal mouse weight [(0.29±0.09) g] and placental weight [(0.06±0.02) g] of surviving fetal mice in the LPS50+NC group on D16.5 and the LPS50+miR-146a-5p agomir group were statistically significant [(0.46±0.06) g, P<0.001; (0.07±0.02) g, P=0.021], and the differences in the number of absorbed embryos and embryo uptake rate between the two groups were not statistically significant (all P>0.05). The expression levels of both pSTAT1 protein and TNFα mRNA were significantly downregulated in BMDM transfected with miR-146a-5p mimics compared with those transfected with NC ( P=0.012, P=0.039). Conclusion:miR-146a-5p expression levels were significantly increased at the maternal-fetal interface during the late stage of mouse embryo implantation and placental development. Exogenous miR-146a-5p could effectively improve LPS-induced mouse embryo resorption and fetal mouse dysplasia. miR-146a-5p could inhibit the M1 polarization activity of mouse macrophages, suggesting that miR-146a-5p may inhibit the M1 polarization activity of mouse macrophages by suppressing M1 polarization of mouse maternal-fetal interface macrophages to safeguard the normal establishment and maintenance of pregnancy.

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of dedifferentiated liposarcoma (DDLPS) with inflammatory myofibroblastic tumor (IMT)-like features. Methods: Five cases of DDLPS with IMT-like features were collected from the First Affiliated Hospital of Nanjing Medical University, the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine and the First People′s Hospital of Qinzhou between 2013 and 2018. EnVision method and fluorescence in situ hybridization (FISH) were used to detect the immunophenotype of the tumor cells and the profile of MDM2 gene amplification respectively. Results: All five cases were male and the median age was 61 (range 53 to 65) years. The clinical symptoms were mainly related to the space-occupying lesions. The tumors were located in duodenal mesentery (two cases), intestinal wall (one case), retroperitoneum (one case), and spermatic cord (one case). Grossly, the tumors were not well encapsulated, ranging from 3 to 13 cm (median 6.7 cm) in diameter, with tan to gray and firm cut surface. Histologically, the dedifferentiated component closely resembled inflammatory myofibroblastic tumor (IMT), with spindle/polygonal/stellate-shaped cells arranged in storiform, sheet-like, or random pattern, with varying degrees of chronic inflammation and fibrosis. All three major patterns seen in IMT (myxoid, cellular and hypocellular fibrous) were observed, the hypocellular fibrous pattern was the most common. Well-differentiated liposarcomatous component was found in the peripheral areas of all the tumors. One case had high grade dedifferentiated component. Four cases were strongly positive for MDM2 and p16. Two cases were positive for SMA, and one case was focally positive for desmin and one for CD34. None of the cases stained for ALK-1. FISH demonstrated MDM2 gene amplification in all five cases. Clinical follow-ups were available in all five cases and the interval ranged from 3 to 66 months (median 23 months). Two patients developed recurrences and one patient had metastasis. The remaining two patients were alive with no evidence of tumor recurrence at 3 and 14 months after surgery respectively. Conclusions DDLPS with IMT-like features is a more aggressive neoplasm than its histological mimic (IMT), and should not be misdiagnosed as other intermediate or low-grade malignant tumors, such as IMT, sclerosing liposarcoma, inflammatory liposarcoma, aggressive fibromatosis, solitary fibrous tumors, low-grade myofibroblastic sarcoma, and low-grade fibrosarcoma.

Objective To investigate the clinicopathological features, diagnosis and differential diagnosis of dedifferentiated liposarcoma (DDLPS) with inflammatory myofibroblastic tumor (IMT)?like features. Methods Five cases of DDLPS with IMT?like features were collected from the First Affiliated Hospital of Nanjing Medical University, the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine and the First People′s Hospital of Qinzhou between 2013 and 2018. EnVision method and fluorescence in situ hybridization (FISH) were used to detect the immunophenotype of the tumor cells and the profile of MDM2 gene amplification respectively. Results All five cases were male and the median age was 61 (range 53 to 65) years. The clinical symptoms were mainly related to the space?occupying lesions. The tumors were located in duodenal mesentery (two cases), intestinal wall (one case), retroperitoneum (one case), and spermatic cord (one case). Grossly, the tumors were not well encapsulated, ranging from 3 to 13 cm (median 6.7 cm) in diameter, with tan to gray and firm cut surface. Histologically, the dedifferentiated component closely resembled inflammatory myofibroblastic tumor (IMT), with spindle / polygonal /stellate?shaped cells arranged in storiform, sheet?like, or random pattern, with varying degrees of chronic inflammation and fibrosis. All three major patterns seen in IMT (myxoid, cellular and hypocellular fibrous) were observed, the hypocellular fibrous pattern was the most common. Well?differentiated liposarcomatous component was found in the peripheral areas of all the tumors. One case had high grade dedifferentiated component. Four cases were strongly positive for MDM2 and p16. Two cases were positive for SMA, and one case was focally positive for desmin and one for CD34. None of the cases stained for ALK?1. FISH demonstrated MDM2 gene amplification in all five cases. Clinical follow?ups were available in all five cases and the interval ranged from 3 to 66 months (median 23 months). Two patients developed recurrences and one patient had metastasis. The remaining two patients were alive with no evidence of tumor recurrence at 3 and 14 months after surgery respectively. Conclusions DDLPS with IMT?like features is a more aggressive neoplasm than its histological mimic (IMT), and should not be misdiagnosed as other intermediate or low?grade malignant tumors, such as IMT, sclerosing liposarcoma, inflammatory liposarcoma, aggressive fibromatosis, solitary fibrous tumors, low?grade myofibroblastic sarcoma, and low?grade fibrosarcoma.

Objective To explore the clinical effects of adjuvant hyperbaric oxygen ( HBO) therapy on peritoneal metastasis of gastric cancer. Methods A retrospective analysis was made on the 88 patients with peritoneal metastasis of gastric cancer admitted to the hospital from August 2014 to August 2016. The patients were divided into the observation group ( n =39 ) and the control group ( n =49 ) by different treatment methods. The control group was treated with chemotherapy, while the observation group received adjuvant HBO therapy in addition to the treatment received by the control group. After 2 courses of treatment, the short-term efficacy and acute and sub-acute toxicity were compared between the patients of the 2 groups, and the life quality of the patients was evaluated by using QLQ-C30. One-year medical follow up was made, and disease progression and survival time were compared between the patients of the 2 groups. Results The objective response rate (ORR) of the observation group and the control group were 53. 85％ and 46. 94％, respectively. There was no statistical difference, when comparison was made between the 2 groups(χ2 =0. 414, P=0. 520). The digestive tract and blood toxicity scores of the observation group were (1. 08 ± 0. 26)and (1. 01 ± 0. 22) respectively, which were significantly lower than (3. 26 ± 0. 62) and (1. 67 ± 0. 41) of the control group (P<0. 05). The median disease progression time of the observation group and the control group was respectively 6 months and 3 months, and the median survival time was respectively 8. 9 months and 5. 1 months, with the observation group all being superior to those of the control group ( P < 0. 05 ). The comprehensive scores of the life quality and physical function in the observation group were higher than those in the control group (P<0. 05). Conclusion HBO adjuvant therapy for gastric cancer patients with peritoneal metastasis has good short-term efficacy, and could slow disease progress, improve their life quality, and more importantly showed less adverse reactions.

Objective To explore the clinical effects of adjuvant hyperbaric oxygen ( HBO) therapy on peritoneal metastasis of gastric cancer. Methods A retrospective analysis was made on the 88 patients with peritoneal metastasis of gastric cancer admitted to the hospital from August 2014 to August 2016. The patients were divided into the observation group ( n =39 ) and the control group ( n =49 ) by different treatment methods. The control group was treated with chemotherapy, while the observation group received adjuvant HBO therapy in addition to the treatment received by the control group. After 2 courses of treatment, the short-term efficacy and acute and sub-acute toxicity were compared between the patients of the 2 groups, and the life quality of the patients was evaluated by using QLQ-C30. One-year medical follow up was made, and disease progression and survival time were compared between the patients of the 2 groups. Results The objective response rate (ORR) of the observation group and the control group were 53. 85％ and 46. 94％, respectively. There was no statistical difference, when comparison was made between the 2 groups(χ2 =0. 414, P=0. 520). The digestive tract and blood toxicity scores of the observation group were (1. 08 ± 0. 26)and (1. 01 ± 0. 22) respectively, which were significantly lower than (3. 26 ± 0. 62) and (1. 67 ± 0. 41) of the control group (P<0. 05). The median disease progression time of the observation group and the control group was respectively 6 months and 3 months, and the median survival time was respectively 8. 9 months and 5. 1 months, with the observation group all being superior to those of the control group ( P < 0. 05 ). The comprehensive scores of the life quality and physical function in the observation group were higher than those in the control group (P<0. 05). Conclusion HBO adjuvant therapy for gastric cancer patients with peritoneal metastasis has good short-term efficacy, and could slow disease progress, improve their life quality, and more importantly showed less adverse reactions.

Objective To evaluate the value of transperineal targeted biopsy with real-time fusion images of transrectal ultrasound (TRUS)and multiparametric magnetic resonance imaging (mpMRI)for the diagnosis of prostate cancer (PCa).Methods Clinical and imaging data of 62 consecutive patients suspected of PCa at the mpMRI scan and PSA>4.0 μg/L were retrospectively analyzed.Targeted biopsies (TB)were carried out for each cancer-suspicious lesion,and followed a systematic 12-core biopsy (SB) protocol.Pathological findings of TB and SB were analyzed.Results The age of the patients was (68.38± 6.57)years (range 5 1 -79 years).The preoperative PSA value was (10.21 ±5.57)μg/L (range 4.5 -30.1μg/L).Preoperative prostate volume was (34.05±9.86)ml (range 19-64 ml).The PCa patients detected by SB and/or TB were 34 (54.8%).Cancer-detected rates of SB and TB cores were 7.53% and 26.2%, respectively (P <0.001).The positive core length of SB and TB cores were (3.71 ±2.77)mm (range 1 -14 mm)and (5.00±3.04)mm (range 2-1 7 mm),respectively (P =0.016).The positive core percent of SB and TB cores were (28.77 ± 20.13 )% (range 7 - 100%)and (35.76 ± 1 8.73 )% (range 1 1 % - 100%), respectively (P =0.048).Moreover,clinically cores detected by the SB and TB for final diagnosis of PCa were 19 cores (2.6%)and 48 cores (1 8.5%),respectively (P < 0.001 ).Conclusions Transperineal TB using real-time TRUS and mpMRI fusion imaging can improve sampling quality and elevate clinically detection rate of PCa when application combined with SB.

Antiviral Agents ; Diabetic Retinopathy ; Drug Combinations ; Hepatitis C, Chronic ; Humans ; Interferon-alpha ; Polyethylene Glycols ; Recombinant Proteins ; Ribavirin