[Correlation of CD4+/CD8+Ratio in Peripheral Blood with Prognosis of Mantle Cell Lymphoma].

OBJECTIVE: To investigate the correlation of peripheral blood T lymphocyte subsets with overall survival (OS) and clinical baseline characteristics in mantle cell lymphoma (MCL). METHODS: The clinical data of 55 MCL patients who were newly diagnosed in the Department of Hematology, Second Hospital of Shanxi Medical University from January 2012 to July 2022 were analyzed retrospectively. The percentages of T lymphocyte subsets and CD4+/CD8+ ratio in peripheral blood were detected by flow cytometry, and their correlation with clinical characteristics of patients were analyzed. Kaplan-Meier method was used for survival analysis and survival curves were drawn. Log-rank test was used for univariate analysis, while Cox proportional hazards model was used for multivariate analysis. RESULTS: The median follow-up was 40(1-68) months, and the median overall survival (OS) was 47 months. Among the 55 patients, 30(54.5%) patients had a decrease in peripheral blood CD4+T lymphocyte, while 17(30.9%) patients had a increase in peripheral blood CD8+T lymphocyte, and 20(36.4%) patients had a decrease in CD4+/CD8+ ratio. There were no significant correlations between CD4+/CD8+ ratio and sex, age, Ki-67, B symptoms, leukocytes, hemoglobin, lymphocytes, platelets, albumin, lactate dehydrogenase (LDH), ß2-microglobulin, splenomegaly, bone marrow invasion, primary site and MIPI score. Survival analysis showed that patients with CD4+T cell >23.3%, CD8+T cell ≤33.4% and CD4+/CD8+ ratio >0.6 had longer OS (P =0.020, P <0.001, P <0.001). Univariate analysis showed that Ki-67>30%, LDH>250 U/L, splenomegaly, bone marrow involvement, CD4+T cells ≤23.3%, CD8+ T cells >33.4%, CD4+/CD8+ ratio ≤0.6 were adverse prognostic factors affecting OS of MCL patients. Multivariate analysis showed that CD4+/CD8+ ratio ≤0.6 (HR =4.382, P =0.005) was an independent adverse prognostic factor for OS of MCL patients. CONCLUSIONS: Low CD4+/CD8+ ratio is associated with poor prognosis in MCL, and the CD4+/CD8+ ratio can be used as an important indicator to evaluate the prognosis risk in MCL patients.

[Clinical Characteristics and Survival Analysis of Patients with Plasma Cell Leukemia].

OBJECTIVE: To investigate the clinical characteristics, therapeutic response and prognosis of patients with plasma cell leukemia (PCL) and improve the understanding of this disease. METHODS: The clinical manifestations, laboratory tests and treatment response of 27 patients with plasma cell leukemia treated in The Second Hospital of Shanxi Medical University from December 2010 to August 2019 were analyzed retrospectively, and their clinical characteristics were summarized. Kaplan-Meier method was used for survival analysis. RESULTS: There were 18 cases of primary plasma cell leukemia (pPCL) and 9 cases of secondary plasma cell leukemia (sPCL). The male to female ratio was 1.7∶1. The median age was 62 years old. The first manifestations were bone pain, fatigue, fever, splenomegaly and bleeding, and a large number of plasma cell infiltration was observed in the morphological examination of peripheral blood and bone marrow cells. 13 cases were detected by immunotyping and all of them expressed CD38/CD138. 8 cases underwent karyotype analysis, and 3 cases were normal, clonal abnormalities occurred in 5 cases. FISH detection was performed in 12 cases, of which 8 cases were abnormal. In 17 cases of bortezomib based chemotherapy, the ovevall response rate was 52.9%, which was higher than that in the non-bortezomib group, but there was no significant difference between the two groups (P =0.242). The overall median survival time of 27 patients was 6.4 months, the median progression-free survival time was 3.5 months, and the median survival time of patients with pPCL and sPCL was 8.2 months and 2.4 months, respectively, the difference between the two groups was statistically significant (P =0.031). CONCLUSION: PCL is highly invasive and has diverse clinical manifestations, and is not sensitive to traditional chemotherapy. The median survival time of patients with pPCL is relatively longer than that of patients with sPCL. The chemotherapy regimen based on bortezomib improves the treatment effectiveness and prolongs the survival time of PCL patients.

[Advances of Sirolimus in the Treatment of Patients with Autoimmune Cytopenia---Review].

Autoimmune cytopenia is a general term for all hemocytopenia diseases caused by humoral or cellular immunity abnormalities, and its common immune mechanism determines the importance of immunosuppressive therapy. Sirolimus, as an immunosuppressant against of mTOR, induces immune tolerance by adjusting Treg cells, which has application prospect in the treatment of refractory autoimmune cytopenia. This article reviews the mechanism, application, and possible adverse reactions of sirolimus in the treatment of idiopathic autoimmune cytopenia.

[Clinical Efficacy of Modified BU/CY as Conditioning Regimen Combined with Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Young Acute Myeloid Leukemia Patients with Low or Intermediate Risk].

OBJECTIVE: To investigate the safety and efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) using modified BU/CY conditioning regimen for young AML patients of low and middle risk in the first complete remission (CR1). METHODS: Ten young AML patients of low and middle risk who did not want to accept allogeneic hematopoietic stem cell transplantation（allo-HSCT）and underwent auto-PBHSCT in CR1 during May 2013 to December 2016 were retrospectively analyzed. From 3 months after auto-PBHSCT, the maintenance therapy with interleukin-2 (IL-2) or IL-2 combined with histamine dihydrochloride was performed for these patients in the next 18 months. The side effects of the conditioning regimen, hematopoietic recovery time, transplant-related mortality (TRM) within 100 days and 1 year after auto-PBHSCT, relapse rate, leukemia-free survival (LFS) rate at 2 years and 3 years, overall survival (OS) were evaluated at 3 years and 4 years. RESULTS: Gastrointestinal side effects were the major non-hematologic toxicity reaction, among which, 7 cases relatively mild and 3 cases displayed moderate, just one case suffered from severe reaction. In 4 cases, the mild liver damage occurred, but no hemorrhagic cystitis occurred. All the patients experienced different kinds of infection, including 5 cases of bloodstream infection, 2 cases of gastrointestinal infection, 3 cases of crissum infection and 2 cases of oral infection. The myeloablative effect occurred in all ten patients. The median times for absolute neutrophil count (ANC)<0.5×109/L and for platelet count <20.0×109/L were 1.5 (0-3) days and 3 (2-5) days after transplantation, respectively. The patients achieved ANC>0.5×109/L at 10 to 19 days, median was 13 days after auto-PBHSCT. The patients achieved platelet count >20×109/L at 10 to 72 days; median was 32 days after auto-PBHSCT. The TRM within 100 days and 1 year after transplantation was 0. The relapse occurred in 2 cases at 6 and 14 months after auto-PBHSCT raspectively. The median follow-up time was 48.1 months, and the median survival time was 54.7 months after transplantation. The 2-year and 3-year LFS were 100% (10 cases) and 80% (8 cases), respectively. The 3-year and 4-year OS were 80% (8 cases) and 70% (7 cases), respectively. CONCLUSION: Modified BU/CY as conditioning regimen for auto-PBHSCT can achieve the myeloablative effect without raising TRM and obtain good LFS and OS. As for young AML patients without high risk, it is a valuable therapeutic option, especially for those lacking the chance of allo-HSCT.

Secretory status of monoclonal immunoglobulin is related to the outcome of patients with myeloma: a retrospective study.

The treatment of multiple myeloma (MM) with proteasome inhibitor (PI) bortezomib has significantly improved the survival of patients with MM. The 26S proteasome inhibitor targets the unfolded protein response (UPR) by inhibiting proteasome degradation of ubiquitinated paraprotein, subsequently leading to the lethal accumulation of paraprotein within the endoplasmic reticulum. According to secretory status of monoclonal immunoglobulin, newly diagnosed MM (NDMM) is divided into measurable and unmeasurable disease, which includes oligosecretory, nonsecretory, and nonproducer myeloma. The present study analyzed the clinical characteristics of 822 patients with NDMM who had either measurable or unmeasurable diseases and received bortezomib- or thalidomide-based therapies. Our results showed that the median progression-free survival (PFS) and overall survival (OS) of patients with MM was significantly longer in patients with measurable disease than those in oligosecretory, nonsecretory, and nonproducer MM (PFS: 27, 18, 19, and 2.0 months, respectively [P < .001]; OS: 51, 30, 22, and 2.0 months, respectively [P < .001]). Within the unmeasurable group, patients with nonproducer myeloma showed the shortest PFS and OS. Importantly, compared with thalidomide treatment, bortezomib significantly improved the PFS and OS of patients with MM with measurable disease (PFS: 25 and 33 months [P = .022], respectively; OS: 41 and 58 months [P < .001], respectively), but not those with unmeasurable disease (PFS: 18 and 16 months [P = .617], respectively; OS: 22 and 27 months [P = .743], respectively). Our results indicate that bortezomib-based therapy performed no better than thalidomide-based treatment in patients with unmeasurable MM. The results need to be confirmed in other patient cohorts, preferably in the context of a prospective trial.

[Antiviral nucleotide-induced dynamic change of HBV DNA and HBsAg and significance of quarterly and annual quantitative measurements over 5-year follow-up of chronic hepatitis B patients].

OBJECTIVE: To analyze the dynamic changes in hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) levels in chronic hepatitis B (CHB) patients following treatment by antiviral nucleotide drugs over a 5-year follow-up period and to assess the clinical significance of quarterly and annual quantitative measurements. METHODS: One-hundred-and-ten patients with CHB were enrolled in the study and administered on-going standard mono-therapy with various antiviral nucleotide drugs. Over a 5-year period, the HBV DNA level was measured by quantitative PCR every three months and the HBsAg levels were measured by chemiluminescence once a year. The dynamic changes in HBV DNA and HBsAg levels were assessed by Chi-squared test and ANOVA. RESULTS: Only 90 of the CHB patients completed the 5-year follow-up and were included in the analysis. The patients who showed HBeAg-positivity at baseline (study start) had higher levels of HBV DNA and HBsAg than the patients showing HBeAg-negativity. In general, the antiviral nucleotide drug therapy induced downward trends in HBsAg and HBV DNA level over time (F = 17.1, 151.53, all P less than 0.05). However, the most robust reduction in HBV DNA occurred during the first year. The HBsAg level followed an opposite trend, with the most robust reductions occurring in the 3rd, 4th and 5th years of treatment. CONCLUSION: Long-term antiviral nucleotide mono-therapies induced decreases in HBV DNA and HBsAg levels in CHB patients, with the former being most reduced in the short-term and the latter in the long-term.

[The relationship between C20orf54 gene rs3746804 position single nucleotide polymorphism and susceptibility to esophageal squamous cell carcinoma].

OBJECTIVE: To explore the association of C20orf54 gene rs3746804 position single nucleotide polymorphism and susceptibility to esophageal squamous cell carcinoma (ESCC). METHODS: Purification of genomic DNA from whole blood was used the Maxwell(16) System. rs3746804 in C20orf54 was detected by direct sequencing in 434 ESCC patients from Changzhi (Shanxi province) and Linzhou (Henan province) and 554 healthy controls from Changzhi, Linzhou and including immigrators from Linzhou to Changzhi. RESULTS: For rs3746804, the genotypic frequencies of CT (37.5% vs 51.0%, 37.5% vs 52.0%), CC (44.2% vs 34.8%, 44.2% vs 33.0%) in Changzhi ESCC patients showed significant differences with healthy Changzhi controls and the healthy immigrator controls (all P < 0.05), and the frequencies of TT (18.3% vs 4.1%) and CC (44.2% vs 54.6%) in Changzhi ESCC patients showed significant differences with Linzhou ESCC patients (all P < 0.05). The genotypic frequencies of TT (4.1% vs 15.0%), CT (41.2% vs 52.0%) and CC(54.6% vs 33.0%) showed significant differences between Linzhou ESCC patients and the healthy immigrator controls (all P < 0.05), and the frequencies of TT (4.1% vs 14.1%) and CC(54.6% vs 34.8%) showed significant differences between Linzhou ESCC patients and Changzhi healthy controls (all P < 0.01). Meanwhile, there were significant differences between ESCC patients (including Changzhi and Linzhou ESCC patients) and healthy controls (including the healthy Changzhi, Linzhou and immigrator controls) in genotypic frequencies of CT (39.2% vs 48.7%) and CC (48.8% vs 38.2%) (all P < 0.01). CT and CT + TT genotype could decrease the risk of ESCC compared with the CC genotype (OR = 0.630, 95%CI 0.481 - 0.826; OR = 0.654, 95%CI 0.507 - 0.844). CONCLUSION: There is a closed relationship between SNP rs3746804 in C20orf54 and susceptibility to ESCC.

[A comparison and significance of plasma riboflavin levels in patients with esophageal squamous cell carcinoma versus Linzhou healthy migrants in Changzhi of Shanxi].

OBJECTIVE: To study the relationship between plasma riboflavin levels and esophageal squamous cell carcinoma. METHODS: We detected and compared plasma concentrations of riboflavin in patients with esophageal squamous cell carcinoma (ESCC) and immigrants of Linzhou living in Changzhi. Plasma riboflavin levels were quantified in 445 ESCC patients, 689 healthy control subjects and 347 immigrants of Linzhou living in Changzhi by using enzyme-linked immunosorbent assay. RESULTS: The plasma riboflavin levels in patients with ESCC were significantly lower than those in the healthy controls and immigrants of Linzhou living in Changzhi [(731.69 ± 330.67) µg/L vs (1090.43 ± 445.08) µg/L, (731.69 ± 330.67) µg/L vs (897.58 ± 177.78) µg/L, respectively, all P < 0.05], and the plasma riboflavin levels of the healthy controls were higher than those in the immigrants of Linzhou living in Changzhi (P < 0.05). CONCLUSION: Patients with ESCC have decreased plasma riboflavin levels as compared with the healthy controls and immigrants of Linzhou living in Changzhi, there exists a lack of riboflavin in ESCC patients, but the specific mechanism needs further study.

[Clinical significance of urine sediment spectrum analyses in crescentic glomerulonephritis].

OBJECTIVE: To explore whether the analyses of urine sediment spectrum contribute to the diagnosis of crescentic nephritis and whether special cells in urine could be a biomarker for the early stage crescentic nephritis. METHODS: Thirty-five patients diagnosed as crescentic nephritis with renal biopsy were recruited. The phase-contrast microscope was used to observe the early morning urine and offer comprehensive descriptions of urine sediment spectrum. And podocalyxin antibody was utilized to detect podocytes in urine and renal specimens by immunohistochemistry. RESULTS: Marked hematuria and casts were present in the urine of crescentic nephritis and "special cells" appeared in over 50% subjects. The detection rates of "special cells" were 75%, 41% and 0 respectively in early, middle and later stages of crescentic nephritis. Podocytes were identified in the urine of 8/9 subjects. CONCLUSIONS: The urine sediment spectrum contributes to the diagnosis of crescentic nephritis. And special cells in urine are helpful to gauge the stage of crescentic nephritis.

JAK2V617F/STAT5 signaling pathway promotes cell proliferation through activation of Pituitary Tumor Transforming Gene 1 expression.

Gain-of-function mutations of JAK2 play crucial roles in the development of myeloproliferative neoplasms; however, the underlying downstream events of this activated signaling pathway are not fully understood. Our experiment was designed and performed to address one aspect of this issue. Here we report that AG490, a potent JAK2V617F kinase inhibitor, effectively inhibits the proliferation of HEL cells. Interestingly, AG490 also decreases the expression of PTTG1, a possible target gene of the aberrant signaling pathway, in a dose- and time-dependent manner. Furthermore, the promoter activity analyses reveal that the inhibition of the PTTG1 expression is affected at the transcriptional level. Thus, our results suggest that the JAK2V617F/STAT5 signaling pathway promotes cell proliferation through the transcriptional activation of PTTG1.

[Urine sediment combined with urine protein as a biomarker for renal injury].

OBJECTIVE: To investigate whether combination of urine sediment and urine protein can predict the renal pathological changes. METHODS: We prepared 146 specimens of routine fresh fasting morning urine. Sediment analysis was performed with phase-contrast microscopy and 24-hour urine protein was measured. Both urine protein and sediment data were integrated to form three urine analysis groups. Urine group I: proteinuria, hematuira, urine white blood cells, red/white cell casts. Urine group II: proteinuria, few cell hyaline/fine granular casts. Urine group III: minor proteinuira, epithelial cells of tubule, granular/cell casts. The renal pathological lesions were predicted before and then confirmed by renal biopsy. Statistical analyses were performed using kappa test, chi-square test, and significance was accepted at P<0.05. RESULTS: After renal biopsy, we identified 95 cases of glomerular lesion with proliferation, 46 cases of glomerular disease without obvious proliferation and 5 cases of tubular interstitial lesion. According to the sediment analysis, only 67 cases (46%) could be attributed to urine group I. When combined with urine protein, we could pick out another 75 cases from urine groups I and II, and 8 cases from urine group III. The combined urine analysis could predict glomerular disease (77.7%). CONCLUSION: Clinically we can take advantage of the combined urine analysis to predict the pathological lesion of kidney disease, which is especially suitable for primary care doctor, who can not perform renal biopsy.

[Effect of neoadjuvant chemotherapy on histologic grade and expression of biological markers in breast cancer].

OBJECTIVE: The aim of this study is to investigate the changes of expression of estrogen receptors (ER), progesterone receptors (PR), Her-2, Ki-67 and histological grade after neoadjuvant chemotherapy in breast cancer. METHODS: Sixty-seven patients with histopathalogically confirmed breast cancer by core needle biopsy received neoadjuvant chemotherapy. The effect of neoadjuvant chemotherapy was assessed according to the criteria of the Japanese Breast Cancer Society: non-effective (G1), mildly effective (G2), moderately effective (G3), markedly effective (G4) and completely effective (G5). All pathological slides were retrospectively reviewed. Immunohistochemical staining (EnVision method) was used to detect the expression of ER and PR, Her-2 and Ki-67. The pre- and post-neoadjuvant chemotherapy status of tumor histological grade, ER and PR, Her-2 and Ki-67 expression in the 49 cases were compared. RESULTS: The effect of neoadjuvant chemotherapy was assessed in 67 patients. There were 5 cases (7.5%) in G1, 19 in G2 (28.4%), 20 in G3 (29.9%), 17 in G4 (25.4%) and 6 in G5 (9.0%), respectively. PR positive rate was 71.4% after chemotherapy versus 91.8% before chemotherapy, with a statistically significant reduction (P = 0.021). However, the ER and Her-2 expression before and after neoadjuvant chemotherapy was stable. Of the patients with invasive ductal carcinoma, 28.6% had histological grade change after neoadjuvant chemotherapy, and 85.7% of patients decreased one grade. The proportion of histological grade change in the G1, G2, G3, G4 were 0, 5.9%, 41.2% and 54.5%, respectively (P = 0.013). The average rate of Ki-67 expression decreased from 28.3% pre-chemotherapy to 11.0% post-chemotherapy (P = 0.011). After the neoadjuvant chemotherapy, the Ki-67 expression rate decreased by > 10%, > 20%, > 30%, > 40% and > 50% in 3 groups (G1 and G2, group G3, group G4 and G5) showed a tendency to be increased, with a significant difference (P < 0.05). CONCLUSION: PR expression in breast cancer decreases after neoadjuvant chemotherapy, while ER and Her-2 expressions remain stable. After neoadjuvant chemotherapy, the histological grade and proliferation index are decreased and correlated with the response to chemotherapy. Therefore, histological grade and proliferation index may be effective complementary factors in assessment of the effectiveness of neoadjuvant chemotherapy.

[Clinical comparison of transvaginal hysterectomy and laparoscopic hysterectomy].

OBJECTIVE: To compare the clinical characteristics of transvaginal hysterectomy (TVH) and total laparoscopic hysterectomy (TLH). METHOD: Clinical data about 301 cases who received TVH and TLH were collected and the hospital stay days, medical expenses, diagnoses, operation and recovery status were compared between TVH and TLH groups. RESULTS: The ratio of cervical atypical hyperplasia (9.64%), multipara (96.45%) in TVH was higher than that in TLH (2.88%, 89.42%). The ratio of adenoma (29.44%), adnexal disease (4.55%), pelvic endometriosis (4.06%), history of cesarean section (7.11%) in TVH were lower than that in TLH (43.27%, 31.73%, 12.50%, 24.04%). The operation time (76 +/- 28) minutes, bleeding during operation (170 +/- 125) ml, additional operations (5.08%), pelvic adhesion (4.57%), loosening of pelvic adhesion (0.51%), the diameter of the largest myoma or adenoma (49 +/- 17) mm, expenses for operation and hospitalization (1073 +/- 203) yuan in TVH were lower than those in TLH, which were (139 +/- 52) minutes, (206 +/- 153) ml, 36.54%, 41.35%, 17.31%, (57 +/- 22) mm, (1526 +/- 676) yuan respectively. The differences were significant (all P < 0.05). There was no difference of the uterine weight, complication and length of hospitalization duration between the two kinds of operation. CONCLUSIONS: TVH is recommended in cases of few pelvic adhesion, or adnexal disease, cervical disease and of multipara. The uterine weight is not a decisive factor.

[A clinical study of the efficacy and safety of secretory human interferon alpha-2a treatment for chronic hepatitis B].

OBJECTIVE: To investigate the efficacy and safety of secreted interferon in treatment of chronic hepatitis B. METHODS: A multi-center randomized open-label controlled clinical trial was carried out. The patients of the study group were treated by secretory human interferon alpha-2a, and the patients of the control group were treated with an ordinary interferon. RESULTS: ALT normalization rate in the secreted interferon group was 48.3% and it was higher at the end of treatment than that of the control group, but there was no difference between the two groups at the end of the follow-up. HBV DNA dropped more in the study drug group, but there was no difference in the normalization rate between the two groups. HBeAg seroconversions in secreted interferon group and in the control interferon group were 19.0% and 18.4% respectively. The safety of the two types of interferon was satisfactory. CONCLUSIONS: Secreted interferon was superior to ordinary interferon in ALT normalization and HBV DNA drop at the end of treatment in chronic hepatitis B patients, but there was no difference at the end of the follow-up. There was also no difference in HBeAg negative and HBeAg seroconversion between the two groups.

[Study of 8,665 cases of the 50 g oral glucose challenge test to screen the gestational diabetes mellitus].

OBJECTIVE: To study the cutoff value, the appropriate time of the 50 g oral glucose challenge test (GCT) to screen the gestational diabetes mellitus (GDM) and to study the importance of the maternal age and body weight of GDM. METHODS: The clinical data of 8 665 pregnant women who underwent the GCT from January 1995 to March 2001 in the Department of Obstetrics and Gynecology of the First Hospital of Beijing University were collected, and a retrospective study was made. RESULTS: (1) The 1 h average plasma glucose level of the GCT is (6.8 +/- 1.7) mmol/L. The abnormal rate of GCT was 25.2% using 7.8 mmol/L as the cutoff, 5.3% (17/321) of GDM were misdiagnosed. When the cutoff is 7.2 mmol/L, the abnormal rate is increased to 36.5%, and 2.8% (9/321) of GDM were more diagnosed. If a value of 8.3 mmol/L as threshold, there would be 15.9% (51/321) of GDM to misdiagnose. (2) When 1 h blood glucose is >or= 11.2 mmol/L, the incidence of GDM is 55.8% (92/165). Among them, 62.0% (57/92) GDM could be diagnosed according to the fasting blood glucose. (3) There were no difference in the rate of abnormal GCT when GCT underwent between 24 and 36 weeks of gestation. (4) The rate of abnormal GCT and the incidence of the GDM are obviously different among the different age groups. The incidence of GDM among the women younger than 25 years old without high risk factors is only 0.3%, obviously lower than the other groups. (5) The average body mass index (BMI) of the women between 26 to 28 weeks of gestation is (24.9 +/- 2.9) kg/m(2). When the BMI is >or= 27.8 (x +/- s), the rate of abnormal GCT and the incidence of the GDM were obviously higher than the other women. CONCLUSIONS: (1) 7.8 mmol/L as the cutoff of the GCT for the screening of GDM is appropriate. When the 1 h blood glucose level is >or= 11.2 mmol/L, fasting blood glucose should first be done to diagnose GDM. (2) It is necessary to screen GDM as soon as possible after 24 weeks of gestation, but for the women with obviously high risk factors GCT should be done before 24 weeks of gestation. (3) Age and obesity are the important risk factors for the GDM. It is not necessary to screen GDM among the pregnant women younger than 25 years old without high risk factors.