Objective:To investigate the expression of keratin 1 (KRT1) and sialyl-Tn antigen (sTn) in cervical squamous cell carcinoma and its possible mechanism.Methods:Six cervical squamous cell carcinoma specimens were collected at the First Affiliated Hospital of Soochow University, Suzhou, China from 2022 to 2023. Spatial transcriptomics analysis was performed on the paraffin sections of 6 patients to analyze the transcriptomes of invasive squamous cell carcinoma and adjacent normal cervical squamous epithelium. The differential gene KRT1 was selected. Kaplan-Meier survival analysis was used to examine the prognostic value of KRT1 in cervical squamous cell carcinoma patients using the TCGA database. The possible downstream molecule sTn was identified according to literature research. Immunohistochemistry was carried out to investigate the expression of KRT1 and sTn proteins in the primary tumor and metastases of cervical squamous cell carcinoma (40 cases with pelvic lymph node metastasis and 30 cases without). Spearman correlation analysis was conducted to analyze the correlation of their expression.Results:The spatial transcriptomic results of the 6 specimens indicated that the level of KRT1 mRNA significantly decreased in cervical squamous cell carcinoma (compared with that in adjacent normal cervical squamous epithelium), while Kaplan-Meier survival analysis revealed that cervical squamous cell carcinoma patients with low KRT1 mRNA levels (versus high) had a worse prognosis. Immunohistochemistry proved that KRT1 expression was significantly lower in cervical squamous cell carcinoma than in adjacent normal squamous epithelium ( P<0.05), but sTn showed the opposite change (increased in carcinoma, P<0.05). The expression changes of KRT1 and sTn were inversely correlated ( r=-0.217, P<0.05). In addition, the expression levels of KRT1 and sTn in lymph node metastases were not significantly different from those in primary tumors. Conclusions:The decreased expression of KRT1 in primary cervical squamous cell carcinoma and lymph node metastasis may promote tumor cell proliferation and inhibit apoptosis by upregulating sTn, contributing to the poor prognosis of advanced cervical squamous cell carcinoma.

AIM:To appraise the bioequivalence and safety of the test preparation of ritonavir tab-lets and the reference preparation(trade name:Norvir?)in healthy adult subjects under fasting and postprandial conditions.METHODS:This study was a randomized,open-label,single-dose,four-period,fully repeated crossover design bioequivalence study protocol.Thirty-six healthy male and female volunteers were enrolled in the fasting and post-prandial conditions,and a single dose of the test preparation and reference preparation was orally administered.We used liquid chromatography-tan-dem mass spectrometry(LC-MS/MS)to finish the bioassay of the drug concentration of ritonavir in plasma.Pharmacokinetic parameters were statisti-cally analyzed using PhoenixWinNonlin8.1 software(Pharsight,USA)and a non-compartmental model.RESULTS:Under fasting conditions,the pharmacoki-netic parameters of the test and reference prepara-tions:Cmax(792.010±369.282)ng/mL and(856.939±394.427)ng/mL,AUC0-t(6 463.043±2 876.849)ng·mL-1·h and(6 907.690±3 046.132)ng·mL-1·h,AUC0-∞(6 603.617±2 916.352)ng·mL-1·h and(7 051.614±3 093.047)ng·mL-1·h.Here are the pharmacokinetic parameters for both the test prep-aration and the reference preparation in the post-prandial condition:Cmax(574.380±289.566)ng/mL and(615.796±297.382)ng/mL,AUC0-t(5 084.796±2 435.557)ng·mL-1·h and(5 414.167±2 416.952)ng·mL-1·h,AUC0-∞(5 219.144±2 487.793)ng·mL-1·h and(5 551.060±2 490.604)ng·mL-1·h.The 90%confidence interval of the geometric mean ratio of AUC0-t,AUC0-∞,and Cmax for the test preparation and reference preparation lied in the equivalent range of statistics.CONCLUSION:The tested preparation was bioequivalent to the reference preparation un-der fasting and postprandial conditions.

Objective:To describes the probability and rate of native liver survival (NLS) in biliary atresia (BA) patients after Kasai portoenterostomy (KPE)over various time periods and analyzes the perioperative factors associated with liver transplantation or death.Methods:A retrospective case-summary.BA patients administrated at the Department of Fetal and Neonatal Surgery in Hunan Children′s Hospital between January 2015 and December 2021.Probability and rate of NLS were calculated by life table.Cox proportional hazards regression model and Logistic model was applied to explore the perioperative factors related to post-Kasai liver transplantation/death.Results:The median age at Kasai surgery was 62 days.The rate of jaundice clearance (JC) was 64.5% within 3 months after Kasai, and 58.3% of the patients had cholangitis.The probability of NLS reached its lowest point in the first 1 year after Kasai (76.2%) and ranged from 93.2% to 98.0% in years 2-8 after Kasai.The rates of NLS in 2 years, 5 years and 8 years were 71.1%, 62.8% and 56.0%, respectively.Cytomegalovirus (CMV) infection before or on the day of Kasai without antiviral treatment can increase the risk of liver transplantation or death[ HR(95% CI): 1.628 (1.081-2.452), P=0.020].Preoperative gamma-glutamyl transferase increased the risk of liver transplantation/death within 1 year after Kasai[ OR(95% CI): 1.001 (1.000-1.001), P=0.021], and early cholangitis was a risk factor for liver transplantation/death within 5 years after Kasai[ OR(95% CI): 1.934 (1.004-3.726), P=0.048].JC within 3 months post-KPE was a protective factor of NLS. Conclusions:The first year after Kasai was the highest risk period for liver transplantation/death, which should be the focus of follow-up management.JC within 3 months after surgery is the protective factor for overall NLS, 1-year NLS and 5-year NLS.

Objective:To describes the probability and rate of native liver survival (NLS) in biliary atresia (BA) patients after Kasai portoenterostomy (KPE)over various time periods and analyzes the perioperative factors associated with liver transplantation or death.Methods:A retrospective case-summary.BA patients administrated at the Department of Fetal and Neonatal Surgery in Hunan Children′s Hospital between January 2015 and December 2021.Probability and rate of NLS were calculated by life table.Cox proportional hazards regression model and Logistic model was applied to explore the perioperative factors related to post-Kasai liver transplantation/death.Results:The median age at Kasai surgery was 62 days.The rate of jaundice clearance (JC) was 64.5% within 3 months after Kasai, and 58.3% of the patients had cholangitis.The probability of NLS reached its lowest point in the first 1 year after Kasai (76.2%) and ranged from 93.2% to 98.0% in years 2-8 after Kasai.The rates of NLS in 2 years, 5 years and 8 years were 71.1%, 62.8% and 56.0%, respectively.Cytomegalovirus (CMV) infection before or on the day of Kasai without antiviral treatment can increase the risk of liver transplantation or death[ HR(95% CI): 1.628 (1.081-2.452), P=0.020].Preoperative gamma-glutamyl transferase increased the risk of liver transplantation/death within 1 year after Kasai[ OR(95% CI): 1.001 (1.000-1.001), P=0.021], and early cholangitis was a risk factor for liver transplantation/death within 5 years after Kasai[ OR(95% CI): 1.934 (1.004-3.726), P=0.048].JC within 3 months post-KPE was a protective factor of NLS. Conclusions:The first year after Kasai was the highest risk period for liver transplantation/death, which should be the focus of follow-up management.JC within 3 months after surgery is the protective factor for overall NLS, 1-year NLS and 5-year NLS.

AIM:To appraise the bioequivalence and safety of the test preparation of ritonavir tab-lets and the reference preparation(trade name:Norvir?)in healthy adult subjects under fasting and postprandial conditions.METHODS:This study was a randomized,open-label,single-dose,four-period,fully repeated crossover design bioequivalence study protocol.Thirty-six healthy male and female volunteers were enrolled in the fasting and post-prandial conditions,and a single dose of the test preparation and reference preparation was orally administered.We used liquid chromatography-tan-dem mass spectrometry(LC-MS/MS)to finish the bioassay of the drug concentration of ritonavir in plasma.Pharmacokinetic parameters were statisti-cally analyzed using PhoenixWinNonlin8.1 software(Pharsight,USA)and a non-compartmental model.RESULTS:Under fasting conditions,the pharmacoki-netic parameters of the test and reference prepara-tions:Cmax(792.010±369.282)ng/mL and(856.939±394.427)ng/mL,AUC0-t(6 463.043±2 876.849)ng·mL-1·h and(6 907.690±3 046.132)ng·mL-1·h,AUC0-∞(6 603.617±2 916.352)ng·mL-1·h and(7 051.614±3 093.047)ng·mL-1·h.Here are the pharmacokinetic parameters for both the test prep-aration and the reference preparation in the post-prandial condition:Cmax(574.380±289.566)ng/mL and(615.796±297.382)ng/mL,AUC0-t(5 084.796±2 435.557)ng·mL-1·h and(5 414.167±2 416.952)ng·mL-1·h,AUC0-∞(5 219.144±2 487.793)ng·mL-1·h and(5 551.060±2 490.604)ng·mL-1·h.The 90%confidence interval of the geometric mean ratio of AUC0-t,AUC0-∞,and Cmax for the test preparation and reference preparation lied in the equivalent range of statistics.CONCLUSION:The tested preparation was bioequivalent to the reference preparation un-der fasting and postprandial conditions.

Objective:To investigate the expression of keratin 1 (KRT1) and sialyl-Tn antigen (sTn) in cervical squamous cell carcinoma and its possible mechanism.Methods:Six cervical squamous cell carcinoma specimens were collected at the First Affiliated Hospital of Soochow University, Suzhou, China from 2022 to 2023. Spatial transcriptomics analysis was performed on the paraffin sections of 6 patients to analyze the transcriptomes of invasive squamous cell carcinoma and adjacent normal cervical squamous epithelium. The differential gene KRT1 was selected. Kaplan-Meier survival analysis was used to examine the prognostic value of KRT1 in cervical squamous cell carcinoma patients using the TCGA database. The possible downstream molecule sTn was identified according to literature research. Immunohistochemistry was carried out to investigate the expression of KRT1 and sTn proteins in the primary tumor and metastases of cervical squamous cell carcinoma (40 cases with pelvic lymph node metastasis and 30 cases without). Spearman correlation analysis was conducted to analyze the correlation of their expression.Results:The spatial transcriptomic results of the 6 specimens indicated that the level of KRT1 mRNA significantly decreased in cervical squamous cell carcinoma (compared with that in adjacent normal cervical squamous epithelium), while Kaplan-Meier survival analysis revealed that cervical squamous cell carcinoma patients with low KRT1 mRNA levels (versus high) had a worse prognosis. Immunohistochemistry proved that KRT1 expression was significantly lower in cervical squamous cell carcinoma than in adjacent normal squamous epithelium ( P<0.05), but sTn showed the opposite change (increased in carcinoma, P<0.05). The expression changes of KRT1 and sTn were inversely correlated ( r=-0.217, P<0.05). In addition, the expression levels of KRT1 and sTn in lymph node metastases were not significantly different from those in primary tumors. Conclusions:The decreased expression of KRT1 in primary cervical squamous cell carcinoma and lymph node metastasis may promote tumor cell proliferation and inhibit apoptosis by upregulating sTn, contributing to the poor prognosis of advanced cervical squamous cell carcinoma.

Purpose To examine the clinicopathologic,immunohistochemical,and molecular genetic characteristics and differential diagnosis of low-grade oncocytic tumor(LOT)of kidney with CK7 positive and CD117 negative,so as to enhance the understanding of this tumor among pathologists.Methods A total of five cases of renal LOT from the First Affiliated Hospi-tal of Soochow University between December 2016 and February 2023 were included in this analysis.The clinicopathological fea-tures,immunophenotype,genetic characteristics,and prognosis were evaluated using HE staing,immunohistochemical staining,and Sanger sequencing.Additionally,relevant literature was re-viewed to supplement the findings.Results Among the cohort of five patients,four were female and one was male,aged 57-70 years with a median age of 65 years and an average age of 64.8 years.Clinical presentation revealed that only the first case exhibited frequent urination accompanied by intermittent lumba-go,while the remaining cases were asymptomatic and incidental-ly discovered.Imaging studies demonstrated space-occupying le-sions with clear boundaries and even internal echoes on B-ultra-sonography,and patchy low-density shadows in the center with obvious edge enhancement on CT.Grossly,the tumor was nodu-lar,with a maximum diameter ranging from 2.1 to 7.6 cm,and an average diameter of 4.04 cm,with a solid section.Micro-scopically,the boundary of LOT was consistently well-defined,with a thick capsule.The arrangement of tumor cells was ob-served to be both dense and sparse,accompanied by fresh bleed-ing foci and proteinoid secretions.Focal lymphocyte aggrega-tion,hepatic plate like and hepatic sinusoid like structures,thick-walled blood vessels,false nodules of tumor cells,and old hemorrhage were also noted.The tumor cells exhibited uniformi-ty in shape,appearing round or polygonal,with eosinophilic and fine granular cytoplasm.The nuclei were of similar size and shape,appearing round or oval with a clear nuclear membrane.The histological features of the tumor included 2-grade small nu-cleoli,perinuclear halos,binuclear cells,and nuclear shrink-age,but no mitotic figures were detected.The immunophenotyp-ic analysis revealed strongly diffuse expression of CK7 in the tumor cells,while CD117 was negative.The Ki67 proliferation index was low.Sanger sequencing identified mutations in mTORC1 pathway genes in four cases,including three mutations in MTOR and one mutation in RHEB.The patients underwent either local or radical nephrectomy,and were followed up for a period ranging from 2 to 52 months,during which all patients re-mained free of recurrence.Conclusion The low-grade,eosino-philic,and rare renal tumor known as LOT exhibits inert behav-ior.At present,the follow-up results show that complete resec-tion of local operation is sufficient,and the prognosis is good.It is important to distinguish this lesion from other eosinophilic re-nal tumors.

Objective:To evaluate the value of prenatal ultrasound in localization, qualitative diagnosis and prognosis of adrenal mass in fetus.Methods:According to the pathological and follow-up results, the clinical data, ultrasonographic features and prognostic results of 43 cases of fetal adrenal mass in Changsha Maternal and Child Health Hospital were collected and analyzed, and statistical analysis was performed.Results:In this group, 43 cases of adrenal mass lesions were detected by prenatal ultrasound in 172 561 fetuses, with a detection rate of 2.49/10 000 (43/172 561). There were 19 cases of adrenal hematoma (5 cases were not excluded as adrenal neuroblastoma), 10 cases of subphrenic free lung, 8 cases of adrenal cyst, 3 cases of adrenal neuroblastoma, and 3 cases of adrenal teratoma. The coincidence rate of prenatal ultrasound diagnosis was 100%. The gestational weeks of isolated lung were earlier than those of neuroblastoma, hematoma, teratoma and cyst ( P=0.035, 0.031, 0.043, 0.025), but there was no significant difference among other groups ( P>0.05). There was no significant difference in tumor diameter among the groups ( P>0.05). The initial finding of subphrenic free lung was the earliest at the gestational week, 43 fetused were born, 18 cases were treated with surgery, 24 cases were observed, 1 case was abandoned for treatment, follow-up found that the prognosis of the other cases were good except for 1 death. Conclusions:Prenatal ultrasound has a good advantage in prenatal diagnosis and differential diagnosis of adrenal mass lesions. The overall prognosis of fetal adrenal masss is good.

Objective To summarize the pathology of congenital intestinal atresia,the incidence and prenatal diagnosis rate of different types,and to analyze the location and type of intestinal atresia as well as the factors that affect the mortality of various types of intestinal atresia.Method We retrospectively analyzed the clinical data of 147 children with congenital intestinal atresia from January 2013 to March 2016,including gender,gestational age,parity,prenatal diagnosis or not,delivery methods,hospital admission,surgical methods,findings during surgery,combined malformations,complications and prognosis.They were analyzed statistically.Result A total of 147 cases,including 69 males and 78 females were enrolled.There were 40 premature infants and 107 full term cases.Twins were found in 3 cases.Hospital admission age range from 1 hour to 62 days;admission weight range from 1 480 g to 4 200 g;32 cases were diagnosed before birth.2 cases were abandoned before surgery because of trisomy 21.Postoperatively,the occlusion sites was confirmed as following:67 cases (46.2％) in ileum,43 cases (29.7％) in jejunum,26 cases (17.9％) in duodenum,and 9 cases (6.2％) in colon.The pathological types were as following:type Ⅰ 42 cases (29.0％),type Ⅱ 8 cases (5.5％),type Ⅲa 65 cases (44.8％),type Ⅲb 15 cases (10.3％) and type Ⅳ 15 cases (10.3％).22 cases (14.9％) were died because of refusal of treatment:7 cases were due to short bowel syndrome and meconium peritonitis,6 cases were due to postoperative chronic pseudo-obstruction,and 5 cases had anastomotic leakage requiring reoperation.1 case had postoperative enterocolitis and gave up treatment,1 case had anastomotic leak and sever systemic post-surgery infection and gave up further treatment,and 2 cases gave up because of 21-trisomy syndrome.Conclusion The operation plan of intestinal atresia should be based on the location and type of the blockade;the location and complications of the blockade (pseudo-obstruction,short bowel syndrome,and anastomotic leakage) are important factors affecting the treatment and prognosis.

Objective To investigate the effect of surgical treatment of necrotizing enterocolitis (NEC) with different surgical ages.Methods From January 2014 to December 2017,105 neonates with NEC in our hospital were divided into early operation group (operation age ＜ 7 days,n =47) and late operation group (7 ＜ operation age ＜ 28 days,n =58).The general data,surgical indications,intraoperative conditions,surgical methods,postoperative complications,and postoperative survival rates were compared between the two groups.Results Among the 105 neonates with NEC,74 were male and 31 were female.The average birth weight was (2 398 ± 927)g,and the average gestational age was (35 ± 4)weeks.Compared with the early operation group,the late operation group had lighter birth weight,smaller gestational age and higher rate of respiratory failure (P ＜ 0.05).There was no significant difference between the two groups in the proportion of surgical indications (diffuse peritonitis,pneumoperitoneum,and medical treatment ineffective) (P ＞ 0.05).The necrosis rate of small intestine in the late operation group was higher than that in the early operation group,but the necrosis rate of small intestine and colon was lower than that in the early operation group (P ＜ 0.05).There was no significant difference in the proportions of the two groups in the surgical methods (enterostomy,intestinal resection and anastomosis and enterostom,exploratory laparotomy,abdominal drainage,and intestinal resection and anastomosis) (P ＞ 0.05).The incidence of intestinal stenosis in early operation group was higher than that in late operation group (P ＜ 0.05).The survival rate of early operation group was 78.7％,while that of late operation group was 63.8％,with no significant difference (P ＞ 0.05).Conclusions The patients with NEC who were operated within 1 week after birth are more common in term infants and with colon necrosis,and are more likely to occur intestinal stenosis after surgery.The patients with NEC who were operated after 1 week of birth are more common in prematures and low-birth-weight patients,and are often associated with respiratory failure.Pneumoperitoneum and diffuse peritonitis are common surgical indications for NEC.Enterostomy is the major surgical method.Choosing the right timing and surgical method can improve the prognosis of patients with NEC.