Anti-phospholipase A2 receptor-associated membranous nephropathy with human immunodeficiency virus infection treated with telitacicept: A case report.

BACKGROUND: The co-occurrence of Anti-phospholipase A2 receptor-associated membranous nephropathy (anti-PLA2R-MN) and human immunodeficiency virus (HIV) infection is a rare clinical scenario, presenting significant challenges in terms of management and treatment. CASE SUMMARY: A 32-year-old Chinese male diagnosed with HIV infection presented with a clinical history of proteinuria persisting for over two years. A kidney biopsy demonstrated subepithelial immune complex deposition and a thickened glomerular basement membrane, indicative of stage I-II membranous nephropathy. Immunofluorescence staining revealed granular deposition of PLA2R (3+) along the glomerular capillary loops, corroborated by a strongly positive anti-PLA2R antibody test (1:320). Initial treatment involving losartan potassium, rivaroxaban, tacrolimus, and rituximab was discontinued due to either poor effectiveness or the occurrence of adverse events. Following a regimen of weekly subcutaneous injections of telitacicept (160 mg), a marked decline in the 24 h urine protein was observed within a three-month period, accompanied by a rise in serum albumin level. No significant reductions in peripheral blood CD3+CD4+T and CD3+CD8+T cell counts were detected. The patient's physical and psychological conditions showed significant improvements, with no adverse events reported during the treatment course. CONCLUSION: Telitacicept might offer a potential therapeutic avenue for patients diagnosed with anti-PLA2R-MN concomitant with HIV infection.

[Survival of children with recurrent medulloblastoma undergoing sequential therapy: an analysis of 101 cases].

OBJECTIVE: To study the clinical features of children with recurrent medulloblastoma (MB) and treatment regimens. METHODS: A retrospective analysis was performed on 101 children with recurrent MB who were admitted to the hospital from August 1, 2011 to July 31, 2017. The children were followed up to July 31, 2020. The Kaplan-Meier method was used for survival analysis. The Cox regression model was used for multivariate regression analysis. RESULTS: Of the 101 children, 95 underwent remission induction therapy, among whom 51 had response, resulting in a response rate of 54%. The median overall survival (OS) time after recurrence was 13 months, and the 1-, 3-, and 5-year OS rates were 50.5%±5.0%, 19.8%±4.0%, and 10%±3.3% respectively. There was no significant difference in the 5-year OS rate between the children with different ages (< 3 years or 3-18 years), sexes, pathological types, or Change stages, between the children with or without radiotherapy before recurrence or re-irradiation after recurrence, and between the children with different times to recurrence (< 12 months or ≥ 12 months after surgery) (P > 0.05). There were significant differences in the 5-year OS rate between the children with or without reoperation after recurrence and between the children with different recurrence sites (P < 0.05). The children with reoperation after recurrence had a significantly longer survival time than those without reoperation (P=0.007), and the risk of death in children undergoing reoperation after recurrence was 0.389 times (95% confidence interval:0.196-0.774) that in children who did not undergo such reoperation. CONCLUSIONS: As for the recurrence of MB, although remission induction therapy again can achieve remission, such children still have a short survival time. Only reoperation can significantly prolong survival time, and therefore, early reoperation can be considered to improve the outcome of children with recurrent MB.

MicroRNAs of bone marrow mesenchymal stem cell-derived exosomes regulate acute myeloid leukemia cell proliferation and apoptosis.

BACKGROUND: Acute myeloid leukemia (AML) is a malignant hematological disease, originating from hematopoiesis stem cell differentiation obstruction and clonal proliferation. New reagents or biologicals for the treatment of AML are urgently needed, and exosomes have been identified as candidate biomarkers for disease diagnosis and prognosis. This study aimed to investigate the effects of exosomes from bone marrow mesenchymal stem cells (BMSCs) on AML cells as well as the underlying microRNA (miRNA)-mediated mechanisms. METHODS: Exosomes were isolated using a precipitation method, followed by validation using marker protein expression and nanoparticle tracking analysis. Differentially expressed miRNAs were identified by deep RNA sequencing and confirmed by quantitative real-time polymerase chain reaction (qPCR). Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt method, and cell cycle progression and apoptosis were detected by flow cytometry. Functional gene expression was analyzed by qPCR and Western blotting (WB). Significant differences were determined using Student's t test or analysis of variance. RESULTS: BMSCs-derived exosomes effectively suppressed cell proliferation (both P < 0.0001 at 10 and 20 µg/mL) and cell cycle progression (P < 0.01 at G0-G1 stage), and also significantly enhanced cell apoptosis (P < 0.001) in KG-1a cells. There were 1167 differentially expressed miRNAs obtained from BMSCs-derived exosomes compared with KG-1a cell-derived exosomes (P < 0.05). Knockdown of hsa-miR-124-5p in BMSCs abrogated the effects of BMSCs-derived exosomes in regulating KG-1a such as the change in cell proliferation (both P < 0.0001 vs. normal KG-1a cell [NC] at 48 and 72 h). KG-1a cells treated with BMSCs-derived exosomes suppressed expression of structural maintenance of chromosomes 4 (P < 0.001 vs. NC by qPCR and P < 0.0001 vs. NC by WB), which is associated with the progression of various cancers. This BMSCs-derived exosomes effect was significantly reversed with knockdown of hsa-miR-124-5p (P < 0.0001 vs. NC by WB). CONCLUSIONS: BMSCs-derived exosomes suppress cell proliferation and cycle progression and promote cell apoptosis in KG-1a cells, likely acting through hsa-miR-124-5p. Our study establishes a basis for a BMSCs-derived exosomes-based AML treatment.

Late-onset severe hepatic sinusoidal obstruction syndrome in an allogeneic stem cell transplant recipient: A case report.

RATIONALE: Hepatic sinusoidal obstruction syndrome (SOS) is a rare and potentially fatal complications after hematopoietic stem cell transplantation (HSCT). Most severe SOS result in multi-organ dysfunction and are associated with a high mortality rate (>80%). PATIENT CONCERNS: A 31-year-old man was diagnosed with chronic myeloid leukemia blast crisis. He presented with severe thrombocytopenia on day 42 post-HSCT (on days +42), gradually developed with painful hepatomegaly, ascites, and weight gain. DIAGNOSES: The abdominal computerized tomography showed hepatomegaly, hepatic congestion, periportal edema, narrow hepatic vein, and ascites suggestive of SOS/hepatic vein occlusion. According to the EBMT revised diagnostic criteria, the patient was diagnosed as late-onset severe SOS. INTERVENTIONS: Comprehensive treatment including low molecular weight heparin was initiated. OUTCOMES: The patient had good response with resolution of his hepatomegaly, increase of platelet, weight and transaminase loss after 4 weeks treatment. LESSONS: In SOS patients with nonspecific clinical and biochemical findings, computerized tomography scans can be useful in differentiating SOS from other complications after HSCT. low molecular weight heparin is effective for the treatment of SOS.

Pol-miR-363-3p plays a significant role in the immune defense of Japanese flounder Paralichthys olivaceus against bacterial and viral infection.

In this study, we examined the function of a Japanese flounder (Paralichthys olivaceus) microRNA (miRNA), pol-miR-363-3p. We found that pol-miR-363-3p targets an ubiquitin-specific protease (USP), USP32. USP is a family of deubiquitinating enzymes essential to the functioning of the ubiquitin proteasome system. In mammals, USP32 is known to be associated with cancer and immunity. In fish, the function of USP32 is unknown. We found that flounder USP32 (PoUSP32) expression was detected in the major tissues of flounder, particularly intestine. In vitro and in vivo studies showed that pol-miR-363-3p directly regulated PoUSP32 in a negative manner by interaction with the 3'UTR of PoUSP32. Overexpression of pol-miR-363-3p or interference with PoUSP32 expression in flounder cells significantly blocked Streptococcus iniae infection. Consistently, in vivo knockdown of pol-miR-363-3p or overexpression of PoUSP32 enhanced dissemination of S. iniae in flounder tissues, whereas in vivo knockdown of PoUSP32 inhibited S. iniae dissemination. In addition, pol-miR-363-3p knockdown also significantly promoted the tissue dissemination of the viral pathogen megalocytivirus, which, as well as S. iniae, regulated pol-miR-363-3p expression. Together these results revealed an important role of pol-miR-363-3p in flounder immune defense against bacterial and viral infection.

[Clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor and prognostic analysis].

OBJCTIVE: To study the clinical effect of surgery combined with chemotherapy and radiotherapy in children with central primitive neuroectodermal tumor (cPNET), as well as the risks factors for poor prognosis. METHODS: A retrospective analysis was performed for the clinical data of 42 children who were diagnosed with cPNET from June 2012 to September 2018. RESULTS: The 42 children had a median overall survival (OS) time of 2.0 years and a median event-free survival (EFS) time of 1.3 years; the 1-, 3-, and 5-year OS rates were 76.2%±6.6%, 41.4%±8.7%, 37.3%±8.8% respectively, and the 1-, 3-, and 5-year EFS rates were 64.3%±7.4%, 32.7%±8.0%, 28.0%±8.1% respectively. The univariate analysis showed that there were significant differences in the OS and EFS rates among the children with different patterns of surgical resection, chemotherapy cycles, and risk grades (P<0.05), and there was also a significant difference in the OS rate between the children receiving radiotherapy and those not receiving radiotherapy (P<0.05). The multivariate Cox regression analysis showed that chemotherapy cycles and risk grade were independent influencing factors for EFS and OS rates (P<0.05). The EFS and OS rates increased with the increase in chemotherapy cycles and the reduction in risk grade. CONCLUSIONS: Multimodality therapy with surgery, chemotherapy, and radiotherapy is an effective method for the treatment of cPNET in children. Early diagnosis and treatment and adherence to chemotherapy for as long as possible may improve EFS and OS rates.

[Effect of bevacizumab in treatment of children with optic pathway glioma].

OBJECTIVE: To investigate the effect of bevacizumab in the treatment of children with optic pathway glioma (OPG). METHODS: A retrospective analysis was performed for the clinical data of 30 children with OPG who underwent chemotherapy. According to whether bevacizumab was used, they were divided into conventional chemotherapy (carboplatin, vincristine and etoposide) group with 12 children and combined chemotherapy (bevacizumab, carboplatin, vincristine and etoposide) group with 18 children. The children were followed up to 6 months after chemotherapy, and the two groups were compared in terms of visual acuity and tumor size before and after chemotherapy and adverse reactions during chemotherapy. RESULTS: The combined chemotherapy group had a significantly higher proportion of children achieving tumor regression than the conventional chemotherapy group (P<0.05), while there were no significant differences between the two groups in the proportion of children with improved visual acuity or adverse reactions (P>0.05). No chemotherapy-related death was observed in either group. CONCLUSIONS: Bevacizumab combined with conventional chemotherapy can effectively reduce tumor size. Compared with conventional chemotherapy, such combination does not increase adverse reactions and can thus become a new direction for the treatment of OPG in children.

[Risk factors for recurrence within 2 years in children with medulloblastoma].

OBJECTIVE: To investigate the risk factors for recurrence of medulloblastoma (MB) within 2 years and their influence on progression-free survival (PFS). METHODS: A retrospective analysis was performed for the clinical data of 123 children with MB who were admitted from January to December, 2017. According to the presence or absence of recurrence, they were divided into recurrence group with 30 children and non-recurrence group with 93 children. The risk factors for recurrence within 2 years were analyzed, and PFS was compared between the children with different risk factors. RESULTS: Large-cell/anaplastic type and M stage were risk factors for MB recurrence within 2 years. The risk of recurrence in the children with M+ MB was 3.525 times that in those with M0 MB, and the risk of recurrence in the children with large-cell/anaplastic MB was 3.358 times that in those with classic MB (P<0.05). The survival analysis showed that the median PFS time was 20 months in the children with M+ MB, and the 20-month PFS rate was 50% ±â€…11% in the children with M+ MB and 81% ±â€…5% in those with M0 MB (P<0.05). The 20-month PFS rate was 80% ±â€…5% in the children with classic MB, 65% ±â€…10% in those with desmoplastic/nodular MB, 86% ±â€…13% in those with MB with extensible nodularity, and 36% ±â€…20% in those with large-cell/anaplastic MB (P<0.05). CONCLUSIONS: Recurrence is an important influencing factor for the prognosis of MB, and M+ stage and large-cell/anaplastic MB are risk factors for recurrence. Children with such risk factors tend to have a low PFS rate.

Circulating CXCR3-CCR6-CXCR5+CD4+ T cells are associated with acute allograft rejection in liver transplantation.

Circulating T follicular helper (cTFH) cells have been demonstrated to be involved in B-cell-mediated alloreactive responses in kidney and liver transplantation; however, whether these cells are involved in acute liver allograft rejection after liver transplantation, and which subsets are involved, remains to be clarified. The present study aimed to investigate the profiles of cTFH cells in acute liver allograft rejection, including the CXC motif receptor 3 (CXCR3)+ chemokine receptor 6 (CCR6)- subset, the CXCR3-CCR6- subset, and the CXCR3-CCR6+ subset. Twelve liver transplant patients with acute rejection (AR) and 20 with no acute rejection (NAR) were enrolled in the study. The results showed that the proportion of CXCR3-CCR6-CXCR5+CD4+ T cells was significantly increased and the proportion of CXCR3-CCR6+CXCR5+CD4+ T cells was significantly decreased in patients with AR compared with patients with NAR. In addition, the proportion of CXCR3-CCR6-CXCR5+CD4+ T cells was positively correlated with the proportion of B cells in patients with AR. The level of serum interleukin (IL)-21 was higher in the AR group than in the NAR groups. Furthermore, the proportion of CXCR3-CCR6-CXCR5+CD4+ T cells was positively correlated with alanine amino transferase (ALT), whereas the proportion of CXCR3-CCR6+ CXCR5+CD4+ T cells was negatively correlated with ALT. B cells and TFH cells were detected in follicular-like structures in liver allograft tissues from patients with AR. These results suggest that CXCR3-CCR6-CXCR5+CD4+ T cells may be involved in acute allograft rejection after liver transplantation.

Reactivation of resolved hepatitis B virus infection combined with nephrotic syndrome in a patient after allogeneic haematopoietic stem cell transplantation.

BACKGROUND: After allogeneic haematopoietic stem cell transplantation (allo-HSCT), Hepatitis B virus reactivation (HBVr) can be observed in patients with previous resolved Hepatitis B virus (HBV) infections. Nephrotic syndrome (NS) is the main clinical manifestation of HBsAg-positive glomerulonephritis. However, the development of HBVr combined with NS after allo-HSCT is uncommon. CASE PRESENTATION: We presented a case of a 47-year-old female with acute myelogenous leukemia who underwent HLA-identical sibling allo-HSCT and achieved leukemia free survival. She had pretransplant serological markers of a resolved HBV infection (HBsAg-negative, anti-HBc and anti-HBs positive). However, she developed HBVr combined with nephrotic syndrome (NS) 16 months after HSCT. Her histological renal lesion was mesangial proliferative glomerulonephritis. IgA+, IgM+, and C1q deposits but not HBV antigens (HBsAg and HBcAg) were identified in her renal biopsy material. Long-term entecavir and immunosuppression resulted in decrease of HBV virus replication, amelioration of proteinuria and stabilisation of renal function. CONCLUSIONS: Entecavir combined with immunosuppression has efficacy in the treatment of HBVr combined with NS after allo-HSCT, but long course of treatment is needed. Closely monitoring and antiviral prophylaxis might be necessary for allo-HSCT recipients to prevent reactivation of resolved HBV infection and its related complications.

A pilot study on the characteristics of circulating T follicular helper cells in liver transplant recipients.

Circulating CD4+CXCR5+ T follicular helper cells (cTfh) have been demonstrated to be involved in B cell-mediated systemic autoimmune diseases and alloreactive responses following kidney transplantation; however, whether cTfh cells are involved in alloreactive responses after liver transplantation (LT) remains unclear. Our present study aimed to investigate the characteristics of cTfh, as well as CXCR3+CCR6-Tfh1, CXCR3-CCR6-Tfh2, and CXCR3-CCR6+Tfh17 subsets in liver allograft recipients. A total of 30 liver transplant recipients were enrolled in this study. The frequencies of cTfh, Tfh1, Tfh2, and Tfh17 subsets, and interleukin (IL)-21-producing Tfh cells in the circulating blood were analyzed by flow cytometry. The capacity of cTfh cells to help B cells differentiate into plasmablasts was determined one day before and one month after LT. The results revealed that the frequency of cTfh cells remained unaltered before and after LT. However, the frequency of the cTfh subsets (e.g., Tfh1 and Tfh2 cells) and B cells were reduced one month after LT. Functionally, the capacity of Tfh cells to produce IL-21 was reduced one month after LT. In addition, cTfh cells exhibited the capacity to help B cells differentiate into plasmablasts in an IL-21-dependent manner in vitro, which was reduced after LT, despite the unaltered production of IgM and IgG by plasmablasts. Thus, our data suggest that cTfh cells may be involved in alloreactive responses following LT via helping B cells differentiate into plasmablasts and plasma cells.

Tuberculosis-associated hemophagocytic lymphohistiocytosis in an umbilical cord blood transplant recipient.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal condition that can be primary or secondary. Secondary HLH due to Mycobacterium tuberculosis (TB) is uncommon. We report a case of tuberculosis-associated HLH in an umbilical cord blood transplant (UCBT) recipient and discuss its clinical characteristics and challenges. METHODS: Hematologic investigations, bone marrow aspirates, Xpert MTB/RIF test of TB with peripheral blood were performed. Immune modulation with anti-TB therapy was initiated. RESULTS: Subsequent treatment with anti-TB treatment resulted rapid clinical response and disease remission. CONCLUSION: It is important to consider TB as one of the underlying cause of HLH in high-risk patients, particularly those in immunodeficient states. Early diagnosis and treatment can improve the survival rates of patients with tuberculosis-associated HLH.

Refractory Dyslipidemia After Liver Transplant: Case Study With Successive Histologic Investigations.

Hyperlipidemia is not unusual in liver transplant recipients, but refractory severe hyperlipidemia is unusual. We treated a 39-year-old man who had severe dyslipidemia after liver transplant. The levels of blood lipids, liver enzymes, and essential indicators of liver pathology were monitored. The first serum sample was collected from the liver recipient 56 days after transplant surgery because samples could not be obtained sooner after the transplant. The levels of liver enzymes and blood lipids were improved with symptomatic treatment but had recurrent fluctuations. Tacrolimus and cyclosporine, even at low doses, may have been the dominant factor affecting the blood lipid levels in the recipient.

[Effect of carnosol against proliferative activity of breast cancer cells and its estrogen receptor subtype's mediation and regulation mechanisms].

Carnosol has been proved to have anti-breast cancer effect in previous research. But its ER subtype's specific regulation and mediation mechanisms remain unclear. The aim of this study is to observe the effect of carnosol on cell proliferation and its estrogen receptor α and ß's specific regulation and mediation mechanisms with ER positive breast cancer T47D cell. With estrogen receptor α and ß antagonists MPP and PHTPP as tools, the MTT cell proliferation assay was performed to observe the effect of carnosol on T47D cell proliferation. The changes in the T47D cell proliferation cycle were detected by flow cytometry. The effect of carnosol on ERα and ERß expressions of T47D cells was measured by Western blot. The findings showed that 1 x 10(-5)-1 x 10(-7) mol x L(-1) carnosol could significantly inhibit the T47D cell proliferation, which could be enhanced by MPP or weakened by PHTPP. Meanwhile, 1 x 10(-5) mol x L(-1) or 1 x 10(-6) mol x L(-1) carnosol could significantly increase ERα and ERß expressions of T47D cells, and remarkably increase ERα/ERß ratio. The results showed that carnosol showed the inhibitory effect on the proliferation of ER positive breast cancer cells through target cell ER, especially ERß pathway. In the meantime, carnosol could regulate expressions and proportions of target cell ER subtype ERα and ERß.

The ratio of circulating regulatory T cells (Tregs)/Th17 cells is associated with acute allograft rejection in liver transplantation.

CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) and Th17 cells are known to be involved in the alloreactive responses in organ transplantation, but little is known about the relationship between Tregs and Th17 cells in the context of liver alloresponse. Here, we investigated whether the circulating Tregs/Th17 ratio is associated with acute allograft rejection in liver transplantation. In present study, thirty-eight patients who received liver transplant were enrolled. The patients were divided into two groups: acute allograft rejection group (Gr-AR) (n = 16) and stable allograft liver function group (Gr-SF) (n = 22). The frequencies of circulating Tregs and circulating Th17 cells, as well as Tregs/Th17 ratio were determined using flow cytometry. The association between Tregs/Th17 ratio and acute allograft rejection was then analyzed. Our results showed that the frequency of circulating Tregs was significantly decreased, whereas the frequency of circulating Th17 cells was significantly increased in liver allograft recipients who developed acute rejection. Tregs/Th17 ratio had a negative correlation with liver damage indices and the score of rejection activity index (RAI) after liver transplantation. In addition, the percentages of CTLA-4(+), HLA-DR(+), Ki67(+), and IL-10(+) Tregs were higher in Gr-SF group than in Gr-AR group. Our results suggested that the ratio of circulating Tregs/Th17 cells is associated with acute allograft rejection, thus the ratio may serve as an alternative marker for the diagnosis of acute rejection.

[Expression of CAS in hepatocellular carcinoma tissues and its relationship with HBV infection].

OBJECTIVE: To explore whether the cellular apoptosis susceptibility (CAS) protein could serve as a pathologic marker for HCC diagnosis and the roles of CAS expression in HBV infection associated HCC. METHODS: The expression of CAS protein in HCC and its paracarcinoma tissues, non-tumor liver cirrhosis and hepatitis tissues were detected by immunohistochemistry. Meanwhile, HBsAg, HBcAg and HBV DNA in HCC tissues with HBV infection were examined by immunohistochemistry and in situ hybridization respectively. RESULTS: The expression of CAS protein was significantly higher in HCC than in its paracarcinomas tissues (P < 0.01), and higher in paracarcinomas tissues than in non-tumor liver cirrhosis and hepatitis tissues (P < 0.01). Poorly differentiated tumors immunochemically stained stronger than moderately or well differentiated (P < 0.01). CAS protein expression was significantly higher in HBV-infected HCC tissues than that of in non-HBV infection (P < 0.01). Meanwhile, in HBV-infected HCC tissues, the staining intensity score of CAS protein in HBV DNA positive HCC tissues was significantly higher than HBV DNA negative tissues (P < 0.05). CONCLUSIONS: Higher expression of CAS protein is found in HCC tissues,and the intensity of CAS protein expression is related closely to tumor differentiation. We suggested that CAS protein might serve as a marker for HCC diagnosis and differentiation estimation, and deduced that CAS might play an important role in the initiation of HBV infection associated HCC through upregulating expression of CAS.

[Clinical and pathological analysis of 100 cases of drug-induced liver injury].

OBJECTIVE: To study the clinical and pathological features of drug-induced liver injury (DILI). METHODS: Liver specimens were obtained through needle biopsies from 100 patients with DILI. The histological preparations of the specimens were stained with haematoxylin eosin, several histochemistry methods, and immunohistochemistry stains. The pathological changes of the livers were analyzed together with the patients's clinical data. The patients were divided into two groups, an acute DILI group (n=39) and a chronic DILI group (n=61), based on their clinical courses and histological changes in their livers. In the chronic DILI group, the clinical courses were longer than 6 months and/or fibrosis or cirrhosis occurred in their liver tissues. RESULTS: Among our cases the leading cause of DILI was Chinese herb medicine, accounting for 21% of the 100 cases; steroids induced cases were 11% of the total. 78% of the patients presented elevated serum transaminases and/or jaundice. The degree of transaminases elevation and the frequency of jaundice happening in the acute group were significantly higher than those in the chronic group (P less than 0.05). The histopathological liver changes in these DILI cases included: (1) necrosis commonly occurred in acinar zone 3, (2) abundant neutrophil and/or eosinophil infiltrations, (3) hepatocytic and/or canalicular cholestasis with little or no inflammation, (4) microvesicular steatosis mixed with macrovesicular steatosis, and (5) presentation of epitheloid cell granuloma. There were no significant differences in liver histopathology between the acute and the chronic DILI groups, except that the fibrosis and the ductular proliferation were different. CONCLUSION: DILI has become a notable liver disease in mainland China, and the use of Chinese herbal medicine must be improved, standardized and regulated more closely.

[Clinical and pathological analysis on characteristics of primary biliary cirrhosis].

OBJECTIVES: To explore the clinical and pathological features and the pathogenesis of primary biliary cirrhosis (PBC) in Chinese Mainland. METHODS: 30 PBC patients were divided into the early group (Scheuer stage I and II, 19 patients) and the late group (Scheuer stage III and IV, 11 patients). The data of clinics and serology were analyzed, and the pathological features of the liver tissues were characterized. The changes of dendritic cells (DCs) and hepatic stellate cells (HSCs) were studied by immunohistochemistry. RESULTS: In all the PBC patients, the rate of the male to the female was 1 to 5, and the average age was 40.6 years. The mean levels of TBiL, ALP and GGT in the sera were (95.9+-88.5) micromol/L, (537.2+-339.2) U/L, and (582.0+-351.2) U/L, respectively. 73.3% patients showed AMA positive, and the level of GGT was positively correlated with the AMA level according to the result of statistical analysis (r=0.778, P=0.000). The symptoms of jaundice and hepatomegaly were presented more commonly in the late group than those in the early group (chi2=5.182, P<0.05; chi2=13.659, P<0.01, respectively). The main changes of morphology of PBC located in portal tracts. The liver tissues in the early stage of PBC showed the damage of bile ducts and obvious proliferation of small bile ducts. The granulomas, the lymphoid follicles and the foamy cells were found in the liver tissues of PBC (2/19 patients, 12/19 patients, and 10/19 patients in the early stage respectively, while 0/11 patients, 4/11 patients, and 3/11 patients in the late stage respectively). There was significant difference between the early stage and the late stage in presence of the lymphoid follicles and the foamy cells (t=4.489, P<0.05; t=4.019, P<0.05, respectively). The biliary pigmentary particles were mainly accumulated in the liver cells around the portal tracts in 90.0% PBC patients, and the accumulation of copper and iron increased, compared with that in normal specimens. The DCs and HSCs located mainly in the portal tracts, especially around the damaged bile ducts. CONCLUSIONS: There are some clinical and pathological characteristics in the patients with PBC. The level of AMA has no direct relationship with the level of transaminase or bilirubin. The proliferated bile ductules may express the antigens which maybe the target of immune attack. As an antigen-presenting cell, DCs may play an important role in the pathogenesis of PBC.

[Clinical pathology and pathogenesis of severe acute respiratory syndrome].

BACKGROUND: To explore the pathological features and pathogenesis of severe acute respiratory syndrome (SARS) to provide evidence for the clinical treatment and prevention of SARS. METHODS: Pathological features of 2 cases of full autopsy and 4 cases of needle biopsy tissue samples from the patients who died from SARS were studied by light and electron microscopy. The distribution and quantity of lymphocyte subpopulations in the lungs and immune organs from SARS patients were analyzed by immunohistochemistry. The location and semi-quantitative analysis of SARS coronavirus in the tissue specimens were studied by electron microscopy, in situ hybridization and immunohistochemistry. RESULTS: In total of 6 cases, diffuse alveolar damage and alveolar cell proliferation were common. The major pathological changes of 2 autopsy cases of SARS in lung tissues were acute pulmonary interstitial and alveolar exudative inflammation, and 2 autopsy and one biopsy lung tissues showed alveolar hyaline membrane formation. Terminal bronchiolar and alveolar desquamation of lung tissues in one autopsy and 2 biopsy cases were noted. Among 6 cases, 2 biopsy cases presented early pulmonary fibrosis and alveolar organization. Meanwhile, the immune organs, including lymph nodes and spleens from 2 autopsy cases of SARS whose disease courses were less than 12 days showed extensive hemorrhagic necrosis, reactive macrophage/histocyte proliferation, with relative depression of mononuclear and granulocytic clones in the bone marrows. However, spleen and bone marrow biopsy tissue samples from 4 dead SARS cases whose clinical course lasted from 21 to 40 days presented repairing changes. SARS coronaviruses were mainly identified in type I and II alveolar epithelia, macrophages, and endothelia; meanwhile, some renal tubular epithelial cells, cardiomyocytes, mucosal and crypt epithelial cells of gastrointestinal tracts, parenchymal cells in adrenal glands, lymphocytes, testicular epithelial cells and Leydig's cells were also detected by electron microscopy combined with in situ hybridization. The semi-quantitative analysis of lymphocyte subpopulations revealed that the proportion of CD8+ T lymphocytes were about 80% of the total infiltrative inflammatory cells in the pulmonary interstitium, with a few CD4+ lymphocytes CD3+, CD4+, CD8+ or CD20+ lymphocyte subpopulations were obviously decreased and there was imbalance in number and proportion, while CD57+, CD68+, S-100+ and HLA-DR+ cells were relatively increased in lymph nodes and spleens. CONCLUSIONS: Histologically, the pulmonary changes could be divided into acute inflammatory exudative, terminal bronchiolar and alveolar desquamative and proliferative repair stages or types during the pathological process of SARS. SARS coronavirus was found in multi-target cells in vivo, which means that SARS coronavirus might cause multi-organ damages which were predominant in lungs. There were varying degrees of decrease and imbalance in number and proportion of lymphocyte subpopulations in the immune organs of the patients with SARS. However, these changes may be reversible. It was found that cellular immune responses were predominant in the lungs of SARS cases, which might play an important role in getting rid of coronaviruses in infected cells and inducing immune mediated injury.

[Cut-off period of subclassification and pathological features of severe hepatitis based on clinical and pathological analyses].

BACKGROUND: To explore the cut-off period of subclassification and pathological features of severe hepatitis (SH). METHODS: Based on combined clinical and pathological analyses, the complete clinical and biopsy or autopsy liver tissues data from 196 cases of patients with severe hepatitis were investigated. Meanwhile, proliferative hepatocytes, cholangioepithelia and collagens were identified by a panel of monoclonal antibodies such as those against albumin, cytokeratin 18,19 and collagen I, III with immunohistochemical method. RESULTS: The clinical and pathological analyses indicated the cut-off periods of acute, subacute and chronic SH (ASH,SSH and CSH) were (13.4+/-7.2) d, (77.4+/-69.3) d and (80.5+/-63.2) d, respectively. Among all SH cases, one case of ASH patient presented clinical manifestation and pathological changes of ASH for 21 days, however, one patient with SSH was demonstrated 12 day course by histological examination. The time of cut-off period between ASH and SSH in child cases was shorter than that in adult cases. Histologically, ASH liver tissues showed massive and/or submassive necrosis caused by one attack, with congestive sinusoid frameworks and proliferative cholangioepithelium-like hepatocytes, while SSH liver tissues presented combined fresh and old submassive or massive necrosis caused by multiple attacks, accompanied by obviously proliferative bile ducts and sinusoid framework collapse.However, the pathological changes of CSH showed ASH- or SSH-like lesions on the background of chronic liver injury. CONCLUSION: Our data indicated that the cut-off period between ASH and SSH is in accordance with the Scheme of Viral Hepatitis Prevention and Therapy, China, published in 2000, but excluded a part of child SH cases. In our study, the authors found a few pathological features in ASH and SSH.