Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Hepatosteatosis is characterized by abnormal accumulation of triglycerides(TG),leading to prolonged and chronic inflammatory infiltration.To date,there is still a lack of effective and economical therapies for hepatosteatosis.Oridonin(ORI)is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia rubescens.In this paper,we showed that ORI exerted significant protective ef-fects against hepatic steatosis,inflammation and fibrosis,which was dependent on LXRα signaling.It is reported that LXRα regulated lipid homeostasis between triglyceride(TG)and phosphatidylethanol-amine(PE)by promoting ATCL and EPT1 expression.Therefore,we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRα-dependent manner,and the results showed the TG reduction and PE elevation.In detail,hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATCL and EPT1 genes,respectively.Taken together,the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRα-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine α-1,3-galactose epitopes (αGal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END⁺/Gal⁺-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-γ). CTLs targeted cells expressing αGal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.

Purpose: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. Methods: We collected and analyzed relevant data related to clinical diagnosis, biological investigation, and molecular determination in nine children carrying these gene mutations, who were from unrelated families in South China. Results: Of the nine patients (five males, four females) with PFIC, one case of PFIC1, four cases of PFIC2, and four cases of PFIC3 were diagnosed. Except in patient no. 8, jaundice and severe pruritus were the major clinical signs in all forms. γ-glutamyl transpeptidase was low in patients with PFIC1/PFIC2, and remained mildly elevated in patients with PFIC3. We identified 15 different mutations, including nine novel mutations (p.R470HfsX8, p.Q794X and p.I1170T of ABCB11 gene mutations, p.G319R, p.A1047P, p.G1074R, p.T830NfsX11, p.A1047PfsX8 and p.N1048TfsX of ABCB4 gene mutations) and six known mutations (p.G446R and p.F529del of ATP8B1 gene mutations, p.A588V, p.G1004D and p.R1057X of ABCB11 gene mutations, p.P479L of ABCB4 gene mutations). The results showed that compared with other regions, these three types of PFIC genes had different mutational spectrum in China. Conclusion The study expands the genotypic spectrum of PFIC. We identified nine novel mutations of PFIC and our findings could help in the diagnosis and treatment of this disease.

Objective To evaluate the clinical effect of Tissue-Link combined with Cusa and Pringle in hepatectomy for primary hepatocellular carcinoma. Methods From January 2013 to January 2017,the clinical data of ninety-six primary hepatocellular carcinoma patients who had received hepatectomy were collected. 45 cases of hepatectomy (control group) were performed by Pringle. The other 51 cases (observation group) were treated with Tissue-Link combined with Cusa. The indexes and survival rates were compared between the two groups during and after operation. Results Compared with the control group, the operation time of the observation group was prolonged ((189. 2±45. 8) min vs. (151. 6±34. 7) min,t = -5. 101),the intraoperative blood loss ((273. 5±141. 6) ml vs. (371. 3±127. 2) ml,t = 7. 396),total bilirubin at seventh days after the operation (( 15. 7 ± 8. 9 ) μmol/ L vs. ( 26. 5 ± 10. 8 ) μmol/ L, t = 5. 320 ) and postoperative albumin supplementation((61. 0±9. 7) g vs. (84. 6±9. 3) g,t = 7. 698) of the observation group decreased. The tumor recurrence rate ( 0 vs. 8. 9% ( 4/ 45)), intrahepatic metastasis rate ( 7. 8% ( 4/ 51) vs. 20% ( 9/ 45)), extrahepatic metastasis rate (3. 9% (2/ 51) vs. 17. 8% (8/ 45)) (χ2 =. 031,6. 315,6. 746) decreased and the differences were statistically significant (P< 0. 05) . The 2 year and 3 year tumor free survival rate (88. 2%, 76. 5%) of the observation group was higher than those of the control group (64. 4%,44. 4%,χ2 = 5. 468, 8. 902),and the total survival rate of 3 year after operation (80. 4%) in the observation group was significantly, higher than that of the control group (51. 1%,χ2 = 4. 896),the difference was statistically significant (P<0. 05) . Conclusion Tissue-Link combined with Cusa is superior to Tissue-Link combined with Pringle in hepatectomy for primary hepatocellular carolnoma. It has less intraoperative blood loss, less damage to liver function and a lower relapse rate of ineisional margin,and the disease-free survival rate and overall survival rate are improved significantly.

Objective To investigate the influence of difference ileocecal junction length on the efficacy of laparoscopic subtotal colectomy combined with antiperistaltic cecorectal anastomosis (LSCACRA) in treatment of slow transit constipation (STC). Methods Ninety- two STC patients undergoing LSCACRA were divided into 2 groups by random digits table method:10-15 cm group (10-15 cm ascending colon preserved above ileocecal junction, 46 cases) and 2-3 cm group (2-3 cm ascending colon preserved above ileocecal junction ,46 cases). All the patients were followed up for 24 months, and the Wexner incontinence score (WIS), ileocecal junction emptying time of barium enema, Wexner constipation score (WCS), abdominal pain intensity score (NRS), gastrointestinal quality of life index (GIQLI), abdominal pain frequency score and abdominal bloating frequency score were compared between 2 groups. Results All the patients successfully completed LSCACRA, with no conversion to open surgery and death occurred. There were no statistical differences in amount of bleeding, operative time, hospitalization time, exhaust time, incidences of postoperative intestinal obstruction and pulmonary infection, defecation time, WIS and abdominal bloating frequency score between 2 groups (P>0.05). The WCS, GIQLI, NRS and abdominal pain frequency scores 6, 12 and 24 months after operation in 2-3 cm group were significantly better than those in 10 - 15 cm group, WCS: (1.7 ± 1.3) scores vs. (4.2 ± 2.3) scores, (1.7 ± 1.1) scores vs. (4.1 ± 1.9) scores, (1.2 ± 0.5) scores vs. (3.9 ± 2.5) scores;GIQLI:(116.8 ± 6.2) scores vs. (98.5 ± 14.7) scores, (122.9 ± 7.5) scores vs. (104.7 ± 16.5) scores, (124.3 ± 5.9) scores vs. (108.3 ± 15.1) scores; NRS: (1.3 ± 0.5) scores vs. (2.5 ± 1.7) scores, (0.9 ± 0.3) scores vs. (2.3 ± 1.4) scores, (0.8 ± 0.3) scores vs. (2.2 ± 1.5) scores;abdominal pain frequency score:(0.9 ± 0.3) scores vs. (1.6 ± 1.2) scores, (0.7 ± 0.3) scores vs. (1.4 ± 1.1) scores, (0.7 ± 0.2) scores vs. (1.2 ± 1.0) scores, and there were statistical differences (P<0.05). The ileocecal junction emptying time of barium enema 24 months after operation in 2-3 cm group was significantly shorter than that in 10-15 cm group: (17.6 ± 8.4) h vs. (21.3 ± 10.8) h, and there was statistical difference (P<0.05). Conclusions STC patients with LSCACRA is safe and effective. The shorter length of ascending colon preserved above ileocecal junction can improve the efficacy of LSCACRA in the treatment of STC and the prognosis of patients. The 2-3 cm length of ascending colon preserved above the ileocecal junction should be recommended.

Objective To discuss the safety and effectiveness of laparoendoscopic single -site surgery (LESS)in cholecystectomy.Methods LESS and conventional laparoscopic(LC)effect were compared and analyzed in cholecystectomy.48 cases were divided into the two groups,24 cases(group LESS)were cheated by laparoendo-scopic single-site surgery;24 cases(group LC)were cheated by laparoscopic cholecystectomy.Contrasted in their operation time,intraoperative amount of bleeding,intraoperative laparotomy rate,body temperature after operation, complications,intestinal recovery time (postoperative exhaust),hospitalization time after operation,postoperative pain index,cosmetic effect,white blood cell (WBC),serum cortisol (Cortisol,Cor),immunoglobulin A (IgA)and comple-ment (C3 ).Results All cases were successful,no cases converted to laparotomy,no postoperative complications.The operation time of group LESS and group LC were (110.2 ±29.3)min and (77.8 ±31.2)min,respectively,the differ-ence was ststictically significant (t=5.07,P<0.05).The intestinal recovery time and hospitalization time after oper-ation in group LESS were less than that in gruoup LC (P<0.05 ).The cosmetic effect in group LESS (3.5 ± 0.5)was higher than that in group LC(2.1 ±0.5)(P<0.05).Cor and C3 in group LESS were higher than those in group LC(P<0.05 ).Conclusion Laparoendoscopic single -site surgery in cholecystectomy is safe and feasible, compared with traditional laparoscopic operation,operation time in LESS is long,but arapid postoperative recovery, beauty effect is obvious.

Objective To explore the effect of pathogenesis,diagnosis,therapy and prevention of portal vein thrombosis(PVT) after devascularization.Methods Data of 86 patients who underwent devascularization because of cirrhotic portal hypertension between January 2009 and December 2014 were retrospectively analyzed.Patients were divided into preventive anticoagulant treatment group (46 cases) and nonpreventive anticoagulant treatment group (40 cases) according to whether or not to receive prophylactic anticoagulant therapy.Compared the causes of PVT and clinical characters.Results The occurrence of PVT was 10.9％ (5/ 46) in preventive anticoagulant treatment group,PVT Ⅰ , Ⅱ, Ⅲ, Ⅳdegree were 2,3,0,0 cases,and that was 32.5％ (13/40) in nonpreventive anticoagulant treatment group, PVT Ⅰ , Ⅱ , Ⅲ, Ⅳ degree were 4,7,2,0 cases, the incidence rate of treatment group was lower than control group (x2 =9.735, P ＜ 0.05).There was no relationship in PVT with sex, age, and intraoperative ligation of splenic artery beforehand (P＞0.05).There were apparent correlation in PVT with centrifugal-flow of portal vein and peak value of platelet count(P＜0.05).All patients discharged uneventfully after anticoagulant treatment, including 2 cases of thrombolytic and 4 cases of blood supply recanalization, no case died from PVT.Conclusion The definite cause of PVT after devascularization is centrifugal-flow of portal vein and the peak value of platelet count (300-499) × 109/L is a pivotal risk factor.The key point of therapy is early diagnosis and early anticoagulant treatment.

Pancreatic adenosquamous carcinoma is a rare exocrine pancreatic cancer,and surgical treatment is the only promising method in survival time extension and life quality enhancement.In July 2013,1 patient with pancreatic adenosquamous carcinoma and sarcomatoid change was admitted to the Shaoxing People's Hospital.A cauda pancreatis cystic nidus was detected by computed tomography 1 year ago,and no any other clinical symptoms were detected.The left upper quadrant of the patient was glutted and unwell,and the levels of CA19-9 and CA125 were 3 630 kU/L and 645 kU/L,respectively.The results of computed tomography and magnetic resonance imaging showed that a huge cystic and solid tumor was located between the cauda pancreatis,the stomach and the spleen;the tumor was mainly cystic and rooted in the tail of the pancreas;the spleen,stomach and surrounding tissues were infiltrated by the tumor.The results of postoperative pathological examination showed that the tumor was pancreatic adenocarcinoma with squamous epithelial differentiation and sarcomatoid change;the invasive squamous carcinoma dominated stomach wall,and the sarcomatoid change dominated spleen and lymph nodes with partial squamous epithelial differentiation and surrounding lymph nodes metastases.Although the surgical resection was complete and the postoperative thymosin injection and traditional Chinese medicine were implemented,tumor recurred at postoperative month 5,and the patient was dead due to cachexia and pernicious anemia at postoperative month 8.The prognosis of patients with pancreatic adenosquamous carcinoma is poor,early detection and surgery are key points for curative effect enhancement.