Purpose To investigate the clinicopathologic features and differential diagnosis of oncocytic variant of medullary thyroid carcinoma (MTC).Methods Morphological,immunohistochemical findings on 3 oncocytic variant of MTC cases and electron microscopic findings on 2 of these 3 cases were studied,with review of the relevant literatures.Results The cytoplasm was abundant,eosinophilic and granular with defined margins.The nuclei were enlarged,round to oval.Prominent nucleoli were identified in some cells.Tumor cells formed sheets,trabeculae or follicles with infiltrative pattern.Immunohistochemically,thyroglobulin (TG) was negative in all 3 cases.Calcitonin was positive in 2 cases and negative in 1 case.Ultrastructurally,a large number of mitochondria and various neuroendocrine granules were found in the 2nd and 3rd cases.Conclusion Oncocytic variant of MTC is very rare with variable histopathologic appearances.It should be considered in diagnosing oncocytic lesions of thyroid.A definite diagnosis can be rendered based on comprehensive findings of the immunohistochemistry,serology study and electron microscopy.It needs to avoid misdiagnosis and missed diagnosis.

COVID-19 ; Humans ; Kidney Transplantation ; Retrospective Studies ; SARS-CoV-2 ; Transplant Recipients

OBJECTIVES: To study the influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks. METHODS: PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, Weipu Database, and SinoMed were searched for randomized controlled trials on umbilical cord milking versus delayed cord clamping in preterm infants with a gestational age of <34 weeks published up to November 2021. According to the inclusion and exclusion criteria, two researchers independently performed literature screening, quality evaluation, and data extraction. Review Manger 5.4 was used for Meta analysis. RESULTS: A total of 11 articles were included in the analysis, with 1 621 preterm infants in total, among whom there were 809 infants in the umbilical cord milking group and 812 in the delayed cord clamping group. The Meta analysis showed that compared with delayed cord clamping, umbilical cord milking increased the mean blood pressure after birth (weighted mean difference=3.61, 95%CI: 0.73-6.50, P=0.01), but it also increased the incidence rate of severe intraventricular hemorrhage (RR=1.83, 95%CI: 1.08-3.09, P=0.02). There were no significant differences between the two groups in hemoglobin, hematocrit, blood transfusion rate, proportion of infants undergoing phototherapy, bilirubin peak, and incidence rates of complications such as periventricular leukomalacia and necrotizing enterocolitis (P>0.05). CONCLUSIONS Compared with delayed cord clamping, umbilical cord milking may increase the risk of severe intraventricular hemorrhage in preterm infants with a gestational age of <34 weeks; however, more high-quality large-sample randomized controlled trials are needed for further confirmation.
Cerebral Hemorrhage ; Constriction ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Pregnancy ; Prognosis ; Umbilical Cord/physiology* ; Umbilical Cord Clamping

Objective:To explore the protective effect and the mechanism of Danggui Shaoyaosan（DSS） on angiotensin Ⅱ （AngⅡ）/transient receptor potential cation channel 6 （TRPC6） pathway in nephrotic syndrome （NS） rats. Method:In animal experiments， doxorubicin （4 mg·kg^-1 for the 1^st week and 2 mg·kg^-1 for the 2^nd week） was injected twice to the tail vein of rats to induce NS model in 160 rats， which were then randomly divided into model group （normal saline）， losartan group （30 mg·kg^-1·d^-1）， and low-（4.3 g·kg^-1·d^-1）， medium-（8.6 g·kg^-1·d^-1）， and high-dose （17.2 g·kg^-1·d^-1） DSS groups. Besides， a normal group was also set. After intervention for four weeks， ultrastructure changes of the kidney were identified by transmission electron microscopy （TEM）. The 24-hour urine protein was detected by kits. Radioimmunoassay was used to detect the content of AngⅡ and Calcineurin （CaN） in plasma. Western blot was used to detect the protein expression of TRPC6， angiotensin Ⅱ type 1 receptor （AT1R）， podocyte slit diaphragm-specific protein （Nephrin）， and cysteine-aspartic acid protease-3 （Caspase-3） in the renal cortex. Immunohistochemistry was used to detect the expression of TRPC6 and AT1R in the slit diaphragm. In cell experiments， AngⅡ stimulated MPC5 podocytes. The cells were randomly divided into a normal group， an AngⅡ group， an AngⅡ+SAR7334 （TRPC6-specific inhibitor） group， an AngⅡ+5%DSS group， an AngⅡ+10%DSS group， and an AngⅡ+15%DSS group. Western blot was used to detect the protein expression of TRPC6， AT1R， Nephrin， and Caspase-3 in podocytes. Result:Compared with the normal group， the model group showed increased 24-hour urine protein content （P<0.01） and AngⅡ and CaN in plasma （P<0.01）， incomplete glomerular structure， the extensive fusion of podocyte process with elevated fusion rate （P<0.01）， increased expression distribution of AT1R and TRPC6 in the renal cortex， and up-regulated protein expression of AT1R， TRPC6， and Caspase-3 in renal tissues （P<0.01）， and reduced Nephrin protein expression （P<0.01）. Compared with model group， the losartan group and the high-dose DSS group exhibited decreased 24-hour urine protein content （P<0.01） and the content of AngⅡ and CaN in plasma （P<0.01）， improved glomerular structure， reduced fusion rate of podocyte process （P<0.01）， diminished expression distribution of TRPC6 and AT1R in the renal cortex， declining protein expression of AT1R， TRPC6 and Caspase-3 in renal tissues （P<0.01）， and elevated Nephrin protein expression （P<0.01）. Additionally， compared with the normal podocytes， AngⅡ-stimulated podocytes showed increased protein expression of AT1R， TRPC6 and Caspase-3 （P<0.01）， and decreased expression of Nephrin （P<0.01）. Compared with the AngⅡ group， the AngⅡ+SAR7334 group displayed reduced protein expression of AT1R， TRPC6， and Caspase-3 （P<0.01） and increased protein expression of Nephrin （P<0.01）. Conclusion:DSS can improve the pathological characteristics of NS presumedly by inhibiting the interaction between AngⅡ and TRPC6 in podocytes and improving the structural integrity of podocytes to repair the damage of glomerular molecular barrier and slow down the progression of NS-induced proteinuria.

Objective: To predict B cell and T cell epitopes of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins. Methods: The sequences of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins which were derived from Orientia tsutsugamushi were analyzed by SOPMA, DNAstar, Bcepred, ABCpred, NetMHC, NetMHC II and IEDB. The 58-kDa tertiary structure model was built by MODELLER9.17. Results: The 22-kDa B-cell epitopes were located at positions 194-200, 20-26 and 143-154, whereas the T-cell epitopes were located at positions 154-174, 95-107, 17-25 and 57-65. The 47-kDa protein B-cell epitopes were at positions 413-434, 150-161 and 283-322, whereas the T-cell epitopes were located at positions 129-147, 259-267, 412-420 and 80-88. The 56-kDa protein B-cell epitopes were at positions 167-173, 410-419 and 101-108, whereas the T-cell epitopes were located at positions 88-104, 429-439, 232-240 and 194-202. The 58-kDa protein B-cell epitopes were at positions 312-317, 540-548 and 35-55, whereas the T-cell epitopes were located at positions 415-434, 66-84 and 214-230. Conclusions: We identified candidate epitopes of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins from Orientia tsutsugamushi. In the case of 58-kDa, the dominant antigen is displayed on tertiary structure by homology modeling. Our findings will help target additional recombinant antigens with strong specificity, high sensitivity, and stable expression and will aid in their isolation and purification.