Objective: To explore the effect of tumor cell perineural invasion on the prognosis of cervical cancer and the early predictive factors of perineural invasion in patients with cervical cancer. Methods: A retrospective a⁃ nalysis was conducted on the clinical , pathological , and survival data of 551 patients with cervical cancer. These patients were categorized into a survival group (n = 477) and a death group (n = 74) . The baseline characteristics of the two groups were compared using independent samples t ⁃tests , Wilcoxon rank⁃sum tests , and chi⁃square tests.Multivariate binary Logistic stepwise regression analysis was employed to identify independent risk factors associated with mortality. In addition , univariate Logistic regression analysis was performed to determine predictive factors for perineural invasion. A predictive model for perineural invasion in cervical cancer was subsequently developed based on the multivariate regression equation , and its predictive accuracy was assessed using the ROC curve. Results: In the basic data of cervical cancer patients , the high level of perineural invasion , lymphatic metastasis and postopera⁃tive pathological stage in pathological data had an impact on the poor prognosis of patients ( P < 0 . 0 5 ) , Lympho⁃vascular space invasion , parametrial involvement , and tumor invasion depth ≥ 1/2 were identified as significant predictors of PNI. The predictive value was the best in the multivariate model ( Area under the curve = 0. 80) . Conclusion Perineural invasion is an independent risk factor for poor prognosis of cervical cancer patients , and the occurrence of perineural invasion can be effectively predicted by the constructed multivariate mode.

Lumbar intervertebral disc degeneration is a common pathological process in the spine,with the main clinical symptoms of low back pain,numbness of lower limbs,and defecation dysfunction.The occur-rence and development of lumbar intervertebral disc degeneration are determined by multiple factors,and the pathophysiological and cellular mechanisms remain to be fully understood.Nucleus pulposus tissue engineering is a new biotherapy that combines biological histology with material science to treat diseases including lumbar inter-vertebral disc degeneration.Clinicians should fully learn the complex relationship between nucleus pulposus tissue engineering and lumbar intervertebral disc degeneration,which will facilitate the clinical treatment of lumbar in-tervertebral disc degeneration,the rehabilitation of lumbar intervertebral disc after treatment,and the prevention of this disease in the population.

Objective To observe the RNA expression level of carbohydrate thiotransferase family(CHSTs)in non-functioning adenoma,and to analyze its clinical significance.Methods Ninety tissue samples of clinical non-functioning adenoma were collected.The mRNA expression levels of CHST1/2/7/8,follicle-stimulating hormone subunit(3(FSHb),POU domain transcription factor 1(POU1F1)and steroid-producing factor 1(SF-1)were detected by real time fluorescence quantitative PCR(RT-qPCR).And receiver operating characteristic(ROC)curve was used to screen the CHST molecule possessing the function for diagnosing CHST molecule differentiated by non-functional adenoma lineage.Results The expression amounts of CHST1 gene and CHST7 gene in the tumors with large volume were higher than those with small tumors(P=0.014,P=0.044),and the CHST2 gene level in female patients was higher than that in male patients(P=0.016),and the CHST8 gene level in invasive tumors were lower than in non-invasive tumors(P=0.044).The grouping was conducted according to the intensity of SF-1 staining,there were statistically signif-icant differences in CHST1/2/7/8 gene levels among all groups(P＜0.05);the grouping was performed ac-cording to the intensity of PIT1 staining,there were statistically significant differences in CHST1/7 gene levels among all groups(P＜0.01).The correlation analysis showed that the CHST1 level was positively correlated with the tumor volume and POU1F1 level(r=0.322,P=0.002;r=0.686,P＜0.001)and negatively corre-lated with the NR5A1 level(r=-0.227,P=0.032).The CHST7 level was positively correlated with the POU1F1 level(r=0.774,P＜0.001);the CHST8 level was positively correlated with the FSHb and NR5A1 levels(r=0.485,P＜0.001;r=0.725,P＜0.001).The area under ROC curve(AUC)of CHST1 for diagno-sing the immature POU1F1 lineage was 0.750(P=0.023).AUC of CHST8 for diagnosing SF-1 lineage was 0.776(P=0.008),and the AUC of CHST1 combined with CHST8 was 0.823(P=0.002).Conclusion The CHST family is involved in the proliferation and differentiation of clinical nonfunctional adenomas.CHST1 combined with CHST8 is valuable in the diagnosis of SF-1 lineage differentiation.

OBJECTIVES: Hereditary spherocytosis (HS) is the most common hereditary defect of the red cell membrane, mainly characterized by anemia, jaundice, and splenomegaly. Due to the atypical clinical manifestations and negative family history of some patients, as well as the low sensitivity and specificity of traditional laboratory examinations, it is easy for it to escape diagnosis or be misdiagnosed. At present, it has been confirmed that the mutation of ANK1, SPTB, SPTA1, SLC4A1 and EPB42 genes can cause the deletion of their corresponding coding proteins, and thus lead to the defect of erythrocyte membrane. This study aims to analyze the feasibility and clinical application value of HS gene diagnosis. METHODS: Data of 26 patients from Hunan, China with HS admitted to the Department of Hematology, Second Xiangya Hospital of Central South University from January 2018 to September 2021 were retrospectively collected, and their clinical manifestations and results of laboratory examinations were analyzed. Next-generation sequencing (NGS) combined with Sanger sequencing were applied. The mutation of HS pathogenic gene and the variation of uridine diphosphate-glucuronosyl transferase 1 family polypeptide A1 (UGT1A1), a key enzyme in the regulation of bilirubin metabolism, were detected. The results of pathogenic gene variations were interpreted pathogenic gene variations in accordance with the Standards and guidelines for the interpretation of sequence variants published by the American College of Medical Genetics and Genomics (ACMG). The clinical characteristics of patients with different gene variants were analyzed, and the clinical diagnosis and genetic diagnosis were compared. RESULTS: Among the 26 patients with HS, there were 23 cases of anemia, 25 cases of jaundice, 24 cases of splenomegaly, and 14 cases of cholelithiasis. There were 16 cases with family history and 10 cases without family history. The results of HS mutation test were positive in 25 cases and negative in 1 case. A total of 18 heterozygous mutations of HS pathogenic genes were detected in 19 families, among which 14 were pathogenic, 1 was likely pathogenic and 3 were of unknown significance. SPTB mutations (12) and ANK1 mutations (4) were the most common. The main variation types were nonsense mutation (9). There were no significant differences in peripheral blood cell parameters and hemolysis indicators between the SPTB mutant group and the ANK1 mutant group (all P>0.05). The rate of splenectomy in ANK1 mutation group was higher than that in SPTB mutation group, and the difference was statistically significant (χ²=6.970, P=0.014). There were no significant differences in peripheral blood cell parameters and hemolysis indicators among different mutation types (nonsense mutation, frameshift mutation, splice site mutation and missense mutation) (all P>0.05). Among the 18 clinically confirmedpatients, there were 17 cases whose diagnosis is consistent with the genetic diagnosis. Eight patients were clinically suspected, and all of them were confirmed by detection of HS gene mutation. Twenty-four patients with HS underwent UGT1A1 mutation detection, among which 5 patients carried UGT1A1 mutation resulting in a decrease in enzyme activity, and 19 patients had normal enzyme activity. The level of total bilirubin (TBIL) in the group with reduced enzyme activity was higher than that in the group with normal enzyme activity, and the difference was statistically significant (U=22, P=0.038). CONCLUSIONS Most patients with HS have anemia, jaundice and splenomegaly, often accompanied by cholelithiasis. SPTB and ANK1 mutations are the most common mutations in HS pathogenic genes among patients in Hunan, China, and there was no significant correlation between genotype and clinical phenotype. Genetic diagnosis is highly consistent with clinical diagnosis. The decrease of UGT1A1 enzyme activity can lead to the aggravation of jaundice in HS patients. Clinical combined gene diagnosis is beneficial for the rapid and precision diagnosis of HS. The detection of UGT1A1 enzyme activity related gene variation plays an important role in evaluation of HS jaundice.
Humans ; Codon, Nonsense ; Hemolysis ; Retrospective Studies ; Splenomegaly ; Bilirubin

A 24-year-old female patient presented with recurrent itchy annular erythema and scales on the trunk and extremities for 9 years. Histopathological study revealed hyperkeratosis with focal parakeratosis, neutrophil aggregation in the stratum corneum, blisters below the stratum corneum, and perivascular infiltration with lymphocytes, a small number of eosinophils and neutrophils in the superficial and middle dermis. Direct immunofluorescence assay showed negative staining for IgG, IgM, IgA and C3. Whole-exome sequencing of the SPINK5 gene showed a missense mutation c.2423C>T (p.T808I) in exon 25, and a splicing site mutation c.2965-1G>A in exon 31. The compound heterozygosity for the two mutations may be the cause of Netherton syndrome in the patient. Based on the clinical manifestations and genetic testing results, the patient was diagnosed with Netherton syndrome.

Objective:To investigate the clinicopathological features, diagnosis and differential diagnosis of primary central nervous system T-cell lymphomas (TPCNSL), and to analyze its biological behavior and prognosis.Methods:Three cases of TPCNSL were collected from September 2014 to September 2019 in the First Affiliated Hospital of Nanjing Medical University. They were evaluated by HE, immunohistochemistry (IHC) and molecular genetics, and the relevant literature was reviewed.Results:Among the 6 816 brain tumors, 97 were primary central nervous system lymphomas (PCNSL), including 3 TPCNSL. There were two male and one female patients, aged 60, 67, and 82 years. Clinically, they were presented with varying degrees of limb numbness and unstable gait. Microscopically, the tumor cells were distributed diffusely or around blood vessels. They showed significant atypia and brisk mitotic activity. By IHC, they were positive for LCA, CD3, CD43, TIA-1, and perforin. Two of three cases were positive for CD5 and granzyme B. T-cell receptor gene rearrangement was clonal. EBER in situ hybridization was negative. The patients were followed for 1 to 6 months; one patient received chemotherapy and died of recurrence 3 months after surgery. One patient died of recurrence 5 months after operation alone. One patient remained recurrence and metastasis free more than 4 months post surgery.Conclusions:PCNSL is uncommon, and most are B-cell lymphomas, while T-cell lymphomas are even rarer. As the latter may show atypical clinical manifestations, diverse histologic morphology and poor prognosis, early diagnosis and timely treatment are particularly important for patients to improve survival.

Objective:To study the clinicopathological characteristics, diagnosis and differential diagnosis of bronchiolar adenoma (BA).Methods:Fifteen cases of BA were collected from the First Affiliated Hospital of Nanjing Medical University, from January 2016 to October 2019. The clinical data, imaging examination, morphology, immunostaining and molecular changes were retrospectively analyzed.Results:There were 3 males, 12 females, most of the patients were female, mainly in middle-aged to elderly (51-77 years). Three had smoking history. The patients usually had no clinical symptoms. Imaging findings were ground-glass and/or lobulated nodules. Grossly, the tumors were gray-whitish, taupe solid or focally microcystic nodules with distinct boundary but no capsule. The maximum diameter was 0.4-2.5?cm (mean 1.0?cm). Histologically, there were glandular, papillary, or flat patterns that were composed of basal cells, mucous cells, ciliated cells and type Ⅱ pneumocytes, some of which showed basal cell proliferation and squamous cell metaplasia. However, there were some cases with few or even without mucous and/or ciliated cells. Immunostaining highlighted the continuous basal cell layer (positive for p63, p40 and cytokeratin 5/6), which was the most important diagnostic evidence. Genetic tests did not show mutation in BRAF or EGFR genes. All patients were followed up for 1-41 months, and they were without recurrence or metastasis.Conclusions:BA is a benign neoplasm that develops in the peripheral lung with good prognosis. Definite diagnosis is very crucial for surgical treatment, especially in frozen consultation. Immunohistochemistry will be helpful if necessary.

Objective To implement the harmonization of thyroid-stimulating hormone(TSH) of Mindray assay system by par-ticipating in harmonization research program of International Federation of Clinical Chemistry (IFCC)-Standardization of Thyroid Function Tests(C-STFT ) .Methods A total of three combinations of TSH reagents and calibrators were used to measure 20 serum samples of healthy human .Within-run precision and batch-to-batch variation were assessed .The concept of harmonization was dem-onstrated by comparing our test results with All Procedure Trimmed Mean (APTM ) provided by IFCC and recalibrating with Mater Calibrators .Results The within-run precision was 1 .96% ,batch-to-batch variation was 0 .47% - 1 .15% ,depending on the level of TSH analyte .There existed a positive bias compared to APTM values .After recalibration with Mater Calibrators and Passing &Bablok regression ,the slope of method comparison was 1 .0 ,and correlation coefficient was more than 0 .975 .Conclusion By using a panel of real human specimen and recalibration based on APTM ,the test results of Mindray assay system could be harmonized with mainstream manufacturers globally .

Objective To explore whether glycyrrhizin has protective effect on acute liver injury in mice by NF‐κB signaling pathway .Methods Totally 200 Kunming mice which the body weight were about 29 -30 g were chose and divided into 4 groups randomly ,50 cases in each group .The first group was the control group;the second group was acute liver injury group induced by CCl4 ;the third group was injected with Stronger Neo‐Minophagen C(SNMC) injection on the basis of second groups;the fourth group was treated with NF‐κB inhibitor (proDTC) on the basis of the third group .After 1 ,3 ,5 d treatment ,the serum expressing levels of ALT ,AST ,total bilirubin ,albumin of mice and prothrombin time were detected ,the Child‐Pugh score was calculated ,and the pathological observation was performed .Results The results showed that ,compared to the first group ,after CCl4 treatment ,the expressing levels of AST ,ALT ,total bilirubin and albumin ,the PT and Child Pugh score all were significantly increased(P<0 .05) , which indicated that the acute liver injury model induced by CCl4 was successfully established .After the treatment of SNMT (CCl4 +SNMT) in mice ,although the level of each index did not return to normal level ,with the extension of treatment time ,the level of each index was also significantly reduced (P<0 .05) .At the same time ,this effect could be reversed by NF‐κB inhibitor proDTC .Conclusion SNMT plays a significantly protective role in acute liver injury via regulating NF‐κB signaling pathway .

Objective To explore the effects of C-pseudonucleosides bearing thiazolidin-4-one as immunostimulants on differentiation and activation of human lymphocytes. Methods Peripheral blood mononuclear cells (PBMC) were isolated from healthy adults,and then incubated with immunostimulants (CH1a,CH2a,CH1b,CH2b and pidotimod).After 48 h,we collected the supernatants and then detected the concentrations of IL-2,IL-4 and IFN-γ using ELISA.After 72 h,the proliferation was detected using MTT method.PBMC incubated with immunostimulants (CH1a,CH2a,CH1b,CH2b and pidotimod),after 72 h,the cultural cells were collected and CD expressions of lymphocytes were analyzed by flow cytometry.Results All samples could stimulate proliferation of T cells.Immunostimulants CH1a,CH2a and pidotimod could elevate the expressions of CD3,CD4,CD19 and CD16CD56,and stimulate the secretions of IL-2 and IFN-γ. Immunostimulants CH1b and CH2b could elevate the expressions of CD3,CD4,CD19 and CD16CD56,and stimulate the secretions of IL-2 and IL-4. Conclusion Immunostimulants CH1a and CH2a could differentiate Th0 into Th1 and promote the proliferation of B cells as well as NK cells.However,immunostimulants CH1b and CH2b could differentiate Th0 into Th2 and promote the proliferation of B cells and NK cells.