Preparation and Application of Monoclonal Antibody Against Human von Willebrand Factor Propeptide / 中国实验血液学杂志

OBJECTIVE@#To develop monoclonal antibodies that can specifically recognize human von Willebrand factor (VWF) propeptide (VWFpp) in plasma, and establish a rapid and reliable method for the detection of VWFpp antigen in plasma by using the double-antibody sandwich ELISA with the obtained anti-VWFpp monoclonal antibody.@*METHODS@#The recombinant human VWFpp (D1 and D2 regions) protein expressed in eukaryotic cells was used as immunogen to immunize BALB/c mice with routine method, so as to obtain clones of fusion cells. After screening and identification, hybridoma cell lines secreting monoclonal antibodies against VWFpp were selected, and then double-antibody sandwich ELISA assay was used to construct VWFpp antigen detection kit for the determination of VWFpp in human plasma. The levels of VWFpp antigen in plasma of 12 leukemia patients who underwent bone marrow transplantation were dynamically detected.@*RESULTS@#Two hybridoma cell lines that can be subcultured continuously and secrete monoclonal antibodies against VWFpp were obtained and named SZ175 and SZ176 respectively. Identified by ELISA and Western blot, the antibodies could both specifically recognize VWFpp but couldn't recognize mature VWF (without propeptide). Based on the principle of double-antibody sandwich ELISA, monoclonal antibodies SZ175 and SZ176 were successfully made into a kit for detecting VWFpp antigen. The plasma VWFpp levels of leukemia patients before and after bone marrow transplantation were dynamically detected. The results showed that the plasma VWFpp levels of the patients after transplantation were significantly higher than those before transplantation.@*CONCLUSION@#Two monoclonal antibodies against VWFpp were successfully prepared, and a double-antibody sandwich ELISA detection kit for VWFpp antigen was constructed, which provides a powerful tool for further study on the biological function of VWFpp, the clinical diagnosis and classification of von Willebrand disease (VWD), and the prognostic monitoring of endothelial injury-related diseases.

Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma / 中华血液学杂志

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

Recent Advances in SARS-CoV-2-Induced Immune Thrombocytopenia --Review / 中国实验血液学杂志

SARS-CoV-2-induced immune thrombocytopenia (SARS-CoV-2-induced ITP) is an autoimmune disease secondary to virus infections. Its diagnosis is often based on exclusion of other possible causes of thrombocytopenia in COVID-19 patients. Common laboratory examinations include coagulation function, thrombopoietin and drug-dependent antibodies. Since both bleeding and thrombosis risks are seen in SARS-CoV-2-induced ITP patients, individual remedy is essential for the treatment of this disease. Because thrombopoietin receptor agonist(TPO-RA) has the side effect of accelerating thrombosis and may aggravate the pulmonary embolism symptoms of patients, it should be used for refractory SARS-CoV-2-induced ITP patients only. This review briefly summarizes the recent research progress in the pathogenesis, diagnosis and treatment of SARS-CoV-2-induced ITP.

Clinical features, gene mutation profile and prognosis analysis of diffuse large B-cell lymphoma complicated with follicular lymphoma / 白血病·淋巴瘤

Objective:To investigate the clinicopathologic characteristics, gene mutation profile and prognostic influencing factors of diffuse large B-cell lymphoma (DLBCL) complicated with follicular lymphoma (FL) (DLBCL/FL).Methods:The clinicopathological data of 50 DLBCL/FL patients admitted to Rui Jin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine from February 2018 to November 2021 were retrospectively analyzed. Targeted sequencing was performed to assess the mutation profile of 55 lymphoma-related genes. The clinicopathological characteristics were summarized to evaluate the short-term therapeutic efficacy of all patients. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS) of patients. Cox regression risk models were used to assess the factors affecting the OS and PFS.Results:Among 50 DLBCL/FL patients, 23 cases (46%) were male, 22 cases (44%) had an international prognosis index (IPI) score ≥ 2 points, 16 cases (32%) were double-expression lymphoma (DEL) and 4 cases (8%) were double-hit lymphoma (DHL). The complete response (CR) and overall response rates were 68% (34/50) and 78% (39/50), respectively after the first-line therapy. The median follow-up time was 23.3 months (5.1-50.9 months). The 2-year OS rate was 82.1% and 2-year PFS rate was 67.1%; and the median OS and PFS were not reached. Targeted sequencing results showed that the mutation frequencies of KMT2D, MYD88, TP53, BTG2, DTX1, EZH2, CD70, CREBBP, DUSP2, HIST1H1C, HIST1H1E and PRDM1 genes in this cohort were more than 15%. Multivariate Cox regression analysis showed that male ( HR = 4.264, 95% CI 1.144-15.896, P = 0.031) and IPI score ≥ 2 points ( HR = 6.800, 95% CI 1.771-37.741, P = 0.007) were independent risk factors of PFS in newly diagnosed DLBCL/FL patients, and TP53 mutation ( HR = 4.992, 95% CI 1.027-24.258, P = 0.046) was an risk influencing factor of OS. Conclusions:The proportion of male and female DLBCL/FL patients is similar, with a small proportion of DHL. Mutations of KMT2D, MYD88 and TP53 genes are commonly found in DLBCL/FL patients. Generally, DLBCL/FL patients can have a high overall response and good prognosis. Male and IPI score ≥ 2 points are the independent risk factors of PFS, and TP53 mutation is an independent risk factor of OS in DLBCL/FL patients.

Characteristics of early changes in corneal epithelial thickness and related influencing factors after femtosecond assisted laser in situ keratomileusis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the characteristics of changes in corneal epithelial thickness at the early postoperative stage of femtosecond assisted laser in situ keratomileusis(FS-LASIK)and its related influencing factors.METHOD: Retrospective study. A total of 120 patients(240 eyes)of myopia undergoing FS-LASIK from May 2021 to June 2022 were selected. The corneal epithelium thickness in the central area, inner ring area, and outer ring area of patients before and at 1d, 1wk, 1 and 3mo after operation was recorded. The relationship between the variation of corneal epithelium thickness and spherical equivalent, optical zone diameter, depth of cut and cutting ratio was analyzed by Pearson correlation.RESULTS: There was no statistical significance in corneal epithelial thickness in the central area, inner ring area and outer ring area at 1d after FS-LASIK compared with that before operation(P>0.05). At 1wk, 1 and 3mo after surgery, the corneal epithelial thickness in the central area, inner ring area and outer ring area increased compared with that before surgery, and the corneal epithelial thickness in the central area and inner ring area at 1 and 3mo after surgery was greater than that in the outer ring area(all P<0.05). The corneal epithelial thickness in the central, inner and outer ring areas of high myopia patients was thicker than that of low and moderate myopia patients before operation. The corneal epithelial thickness in the central, inner and outer ring areas of high myopia patients was thinner than that of low and moderate myopia patients at 1wk after operation(P<0.05). At 1 and 3mo after operation, the corneal epithelial thickness in the central, inner and outer ring areas of patients with high myopia was greater than that of patients with low and moderate myopia, and the changes of corneal epithelial thickness in the central, inner and outer ring areas were greater than those of patients with low and moderate myopia(P<0.05). The results of Pearson correlation showed that the changes in corneal epithelial thickness in the central and inner ring area were positively correlated with the corneal curvature, depth of cut and cutting ratio at 3mo after surgery, and they were in negative correlation with the age, spherical equivalent and optical zone diameter(P<0.05).CONCLUSION: The corneal epithelial thickness of patients thickened after the FS-LASIK operation, and it was correlated with age, corneal curvature, preoperative depth of cut, cutting ratio, spherical equivalent and the optic zone diameter.

Clinicopathologic characteristics and prognostic analysis of testicular diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

Linderae Radix water extract treats diarrhea-predominant irritable bowel syndrome in rats: a serum metabolomics study / 中国中药杂志

This study aims to investigate the mechanism of Linderae Radix water extract(LRWE) in the prevention and treatment of diarrhea-predominant irritable bowel syndrome(IBS-D) based on serum metabolomics. Eighteen 2-week-old male SD rats were randomized into control, IBS-D model, and LRWE groups. The rats in other groups except the control group received gavage of senna concentrate combined with restraint stress for the modeling of IBS-D. The rats in the LRWE group were administrated with LRWE(5.4 g·kg~(-1)) by gavage, and those in the control and IBS-D model groups with an equal volume of distilled water for a total of 14 days. The visceral sensitivity was evaluated by the abdominal withdrawal reflex(AWR) score, and the degree of diarrhea was assessed by the fecal water content(FWC). The morphological changes of the colon and the morphology and number of goblet cells were observed by hematoxylin-eosin(HE) and periodic acid-schiff(PAS) staining, respectively. Ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was used for the screening of the potential biomarkers in the rat serum and their related metabolic pathways. The results showed that LRWE reduced the AWR score, decreased FWC, and alleviated visceral sensitivity and diarrhea symptoms in IBS-D rats. HE and PAS staining showed that LRWE mitigated low-grade intestinal inflammation and increased the number of mature secretory goblet cells in the colonic epithelium of IBS-D rats. A total of 25 potential biomarkers of LRWE in treating IBS-D were screened out in this study, which were mainly involved in riboflavin, tryptophan, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, and cysteine and methionine metabolism. The regulatory effects were the most significant on the riboflavin and tryptophan metabolism pathways. LRWE may alleviate the visceral hypersensitivity by promoting energy metabolism and amino acid metabolism, enhancing intestinal barrier function, and improving intestinal immune function in IBS-D rats.

Effect and mechanism of ionizing radiation on ferroptosis in mouse hepatocytes / 中华放射肿瘤学杂志

Objective:To investigate the effect and mechanism of ionizing radiation on ferroptosis in mouse hepatocytes.Methods:Twenty-four C57BL/6J mice were divided into two groups by random number table method: healthy control group (control group, n=6) and irradiation group (whole liver was irradiated with a single dose of 30 Gy X-ray, n=18). Mice were sacrificed at 6, 24 and 72 h (6 mice per time point) after irradiation to obtain liver tissue and plasma samples. The contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma were measured by automatic biochemical analyzer. The prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured by automatic biochemical analyzer. Pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. The iron deposition in liver tissues was detected by Prussian blue staining. The expression levels of 4-Hydroxynonenal (4HNE) and hepcidin in the liver were determined by immunohistochemical staining, and quantitative analysis was performed. Plasma malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC) and glutathione (GSH) content were determined by microplate reader analysis according to the kit instructions. The expression levels of transferrin receptor 1 (TfR1), p53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in the liver were measured by Western blot. Results:Compared with the control group, the plasma contents of ALT ( t=5.15, 5.47, both P<0.001) , AST at 6 and 24 h after irradiation were increased ( t=8.42, 2.50, both P<0.001), the plasma PT was prolonged ( t=3.12, P=0.011) and the APTT was shortened ( t=3.26, P=0.009) at 72 h after radiation in the irradiation group. Histopathological results showed that evident liver edema was observed at 6, 24 and 72 h after irradiation ( t=9.58, 10.09, 18.70, all P<0.001). Different degrees of iron deposition were observed ( t=8.57, 15.31, 32.11, all P<0.001). The infiltration of hepcidin positive cells was significantly increased after irradiation ( t=5.36, 13.17, 17.11, all P<0.001). The number of 4HNE positive cells was significantly increased ( t=18.86, 22.67, 9.12, all P<0.001). At the same time, ionizing radiation induced a significant increase in plasma MDA content ( t=4.36, 7.47, 8.22, all P<0.001), and a decrease in SOD ( t=4.52, 5.80, 7.60, all P<0.001), T-AOC ( t=13.24, 20.49, 24.96, all P<0.001) and GSH ( t=2.78, 6.07, 11.25, P=0.020, <0.001, <0.001), respectively. The expression level of TfR1 protein was significantly up-regulated ( t=3.46, 5.40, P=0.026, 0.006), whereas that of GPX4 protein was significantly down-regulated ( t=11.88, 30.63, both P<0.001) at 24 and 72 h after irradiation. At 6, 24 and 72 h after irradiation, the expression level of p53 protein was significantly up-regulated and maintained at a high level ( t=7.84, 4.25, 8.22, P=0.001, 0.013, 0.001), while that of SLC7A11 protein was significantly down-regulated ( t=9.29, 19.96, 9.09, all P<0.001). Conclusion:Ionizing radiation induces the ferroptosis in hepatocytes, and its mechanism may be related to the activation of p53-SLC7A11-GPX4 pathway.

Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease / 神经科学通报·英文版

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

Effects of CDA-G208A gene polymorphism on the efficacy of gemcitabine in the first-line treatment of lung squamous cell carcinoma / 中国临床药理学与治疗学

AIM: To investigate the effect of CDAG208A gene polymorphism on the efficacy and safety of gemcitabine in the first-line treatment of lung squamous cell carcinoma. METHODS: Sixty-five first-line treated patients with locally advanced or metastatic lung squamous cell carcinoma in The First Affiliated Hospital of Wannan Medical College hospital were screened. Group A included 31 patients tested with the GG (wild homozygous) CDAG208A gene, and group B included 34 patients without testing. All patients received gemcitabine plus platinum chemotherapy for at least 2 cycles. The efficacy and safety were evaluated following the RECIST 1.1 standard and the NCI-CTC 5.0 standard, respectively. The primary study endpoint was progression-free survival (PFS), overall survival (OS) and the secondary study endpoints included objective effective rate (ORR), disease control rate (DCR), adverse reactions, and influencing factors of PFS. RESULTS: The results showed that the DCR was 74.5% and 50% in group A and group B, respectively (P=0.045); mPFS was 6.1 months and 5.0 months in group A and group B, respectively (P=0.034); and the mOS was 13.3 months and 12.0 months in group A and group B, respectively, and there was no statistical difference (P=0.388). The number of cases of grade III-IV neutropenia in group A and group B was 2 and 10, respectively (P=0.017); grade III-IV neutropenia was an independent prognostic factor affecting patients with PFS (P=0.045); the group with unknown G208A gene status was more likely to develop grade III-IV neutrophils (P= 0.029). The AUC of CDA-G208A gene predicting neutropenia caused by gemcitabine chemotherapy was 0.756. CONCLUSION: Non-GG type of CDAG208A gene can reduce the metabolic rate of gemcitabine in the body and cause neutropenia after chemotherapy. In severe cases, it can indirectly reduce the clinical efficacy of gemcitabine. The detection of CDA-G208A gene status before treatment can predict the neutropenia caused by gemcitabine chemotherapy.

Serum osteocalcin and diabetic peripheral neuropathy in male patients with diabetes / 中华内分泌代谢杂志

Objective:To investigate the association between serum bone turnover marker osteocalcin and the distal symmetric poly neuropathy(DSPN) in male diabetic patients.Methods:Clinical data from 370 male diabetic patients who admitted to Zhongshan Hospital, Fudan University from January 2020 to November 2021 were collected. These patients were grouped into tertiles by serum osteocalcin level: T1 group(osteocalcin<9.2 ng/mL, n=123), T2 group(osteocalcin 9.2-13 ng/mL, n=122), and T3 group(osteocalcin≥13 ng/mL, n=125). The percentage ratios of DSPN were compared among these groups. Using logistic regression model, the adjusted odds ratio ( OR) for DSPN was calculated. Results:There were 50(40.7%), 29(23.8%), 49(39.2%) patients with DSPN in T1, T2, and T3 group respectively. The ratio of patients with DSPN in osteocalcin T2 group were lower than that in the T1 and T3 groups. Further logistic regression showed a 133.9%( OR=2.339, 95% CI 1.097-4.988, P=0.028) and a 134.2%( OR= 2.342, 95% CI 1.040-5.275, P=0.039) increased risk for DSPN in the T1 and T3 group respectively compared with the T2 group, even after adjusted for age, diabetic duration, HbA 1C, diabetic complications, β cross-linked C-telopeptide of type Ⅰ collagen(CTXβ), 25-hydoxy vitamin D(25-OHD), bone mineral density, and treatment. Conclusions:The serum levels of bone turnover marker osteocalcin were associated with the occurrence of DSPN in male diabetic patients, a moderate level of bone turnover(the serum osteocalcin level of between 9.2 and 13 ng/mL for instance) might be protective for male diabetic patients from DSPN.

Progress of prostate cancer research at the 2022 American Urological Association annual meeting / 中华泌尿外科杂志

Prostate cancer research at the American Urological Association's 2022 annual meeting was extensive, ranging from basic to clinical. This paper summarizes the research progress of surgical treatment, preoperative diagnosis and artificial intelligence prediction model. Understanding the new research progress and ideas proposed in the conference will help guide the clinical work of specialists and researchers to carry out further exploratory research work.

Recombinant human ADAMTS13 ameliorates radiation-induced intestinal injury by regulating inflammation and oxidative stress / 中华放射医学与防护杂志

Objective:To study the protective effect of recombinant human ADAMTS13 (rhADAMTS13) on radiation-induced intestinal injury.Methods:Thirty C57BL/6 J mice were randomly divided into healthy control group, 12 Gy abdominal irradiation group (simple irradiation group) and rhADAMTS13 combined with 12 Gy irradiation group (combined group) with 6, 12 and 12 mice per group. The combined group was given 2.5 μg/kg rhADAMTS13 via tail vein injection 3 d before irradiation. 12 Gy X-ray abdominal irradiation was given to the simple irradiation group.The mice were executed at 1 and 3 d after irradiation, and plasma vWF, ADAMTS13 and CRP concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Intestinal histopathological changes were observed by hematoxylin-eosin (HE) staining.Intestinal Ki67, TNF- α and MPO expression levels were detected by immunohistochemical staining.Plasma malondialdehyde (MDA), superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) were measured by biochemical kits.Results:Compared with the healthy control group, the plasma vWF level was increased( t=6.20、12.29, P<0.05) and ADAMTS13 level was decreased( t=9.82、22.83, P<0.05)in mice at 1(1.38±0.11)and 3 (1.70±0.10)after irradiation.Compared with the simple irradiation group, the plasma vWF level was reduced ( t=2.93, 3.96, P<0.05) and ADAMTS13 level was increased ( t=5.09, 9.82, P<0.05) in mice at 1 (1.23±0.12) and 3 d (1.48±0.09) after irradiation in the combined group. Immunohistochemical staining showed that the number of Ki67 + cells in the crypt of the combined group increased significantly ( t=9.82, P<0.05) and the degree of TNF-α and MPO infiltration decreased significantly ( t=15.44, 14.33, P<0.05) compared with the simple irradiation group.In addition, rhADAMTS13 intervention significantly reduced plasma CRP ( t=5.02, 2.96, P<0.05) and MDA ( t=2.47, 2.55, P<0.05), but increased SOD activity ( t=2.64, 5.64, P<0.05) and T-AOC ( t=3.05, 5.07, P<0.05). Conclusions:rhADAMTS13 attenuates radiation-induced intestinal injury in mice by reducing the levels of inflammation and oxidative stress, providing a new strategy for the protection of radiation-induced intestinal injury.

Relationship between prognosis and different surgical treatments of zygomatic defects: A retrospective study / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effect and summarize the characteristics of different treatment methods in repairing zygomatic defect.@*METHODS@#A total of 37 patients with zygomatic defect were reviewed in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from August 2012 to August 2019. According to the anatomical scope of defect, the zygomatic defects were divided into four categories: Class 0, the defect did not involve changes in zygomatic structure or continuity, only deficiency in thickness or projection; Class Ⅰ, defect was located in the zygomatic body or involved only one process; Class Ⅱ, a single defect involved two processes; Class Ⅲa, referred to a single defect involving three processes and above; Class Ⅲb, referred to zygomatic defects associated with large maxillary defects. The etiology, defect time, defect size and characteristics of zygomatic defects, the repair and reconstruction methods, and postoperative complications were collected and analyzed. Postoperative computed tomography (CT) data were collected to evaluate the outcome of zygomatic protrusion. Chromatographic analysis was used to assess the postoperative stability.@*RESULTS@#Among the causes of defects, 25 cases (67.57%) were caused by trauma, and 11 cases (29.73%) were of surgical defects following tumor resection. We performed autologous bone grafts in 19 cases, 6 cases underwent vascularized tissue flap, 5 cases underwent external implants alone, and 7 cases underwent vascularized tissue flap combined with external implants. After the recovery of the affected side, the average difference of the zygomatic projection between the navigation group and the non-navigation group was 0.45 mm (0.20-2.50 mm) and 1.60 mm (0.10-2.90 mm), with a significant difference (P=0.045). Two patients repaired with titanium mesh combined with anterolateral thigh flap had obvious deformation or fracture of titanium mesh; 2 patients with customized casting prosthesis had infection after surgery and fetched out the prosthesis finally.@*CONCLUSION@#Autologous free grafts or alloplastic materials may be used in cases without significant structural changes. Pedicle skull flap or vascularized bone tissue flap is recommended for zygomatic bone defects with bone pillar destruction, chronic inflammation, oral and nasal communication or significant soft tissue insufficiency. Titanium mesh can be used to repair a large defect of zygomatic bone, and it is suggested to combine with vascularized bone flap transplantation.

Clinicopathological characteristics and prognostic analysis of patients with female genital tract diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the clinicopathological characteristics, gene mutation profile, and prognostic factors of diffuse large B-cell lymphoma (DLBCL) in female genital tract.Methods:A retrospective analysis was performed on the clinicopathological data of 30 patients with female genital tract DLBCL who were admitted to Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from October 2003 to October 2021. Targeted sequencing was used to detect 55 lymphoma-related genes, and the gene mutation status of patients was evaluated. Kaplan-Meier method was used for survival analysis, and prognostic factors were analyzed by Cox proportional hazards model.Results:The median age of 30 female genital tract DLBCL patients at diagnosis was 58 years old (23-77 years old). The initial symptoms mainly included abdominal pain, distension, and masses (8 cases, 32%). Tumors most commonly located in the adnexal region (including ovaries and fallopian tubes) (13 cases, 45%), of which 9 cases were unilateral. Twenty-one cases (70%) had multiple extra-nodal involvements, 22 cases (73%) had Ann Arbor stage Ⅲ-Ⅳ, 8 cases (27%) had Eastern Cooperative Oncology Group (ECOG) score of ≥2, and 22 cases (73%) had elevated lactate dehydrogenase (LDH), 21 cases (70%) had International Prognostic Index (IPI) score of 3-5. Within 30 patients, 11 patients (37%) received surgery, and all patients received R-CHOP regimen-based chemotherapy. All 30 cases were evaluated for efficacy, the complete remission rate was 83% (25/30), the 5-year progression-free survival (PFS) rate was 69.7%, and the 5-year overall survival (OS) rate was 79.6%. Univariate analysis showed that ECOG score ≥2 was associated with worse OS ( P = 0.048). Among the 30 patients, 7 patients (23%) were primary and 23 patients (77%) were secondary. The proportions of patients with Ann Arbor stage Ⅲ-Ⅳ, IPI score 3-5 and elevated LDH in secondary patients were higher than those in primary patients (all P < 0.001), but there were no significant differences in PFS and OS between the two ( P values were 0.261 and 0.671). The targeted sequencing results of 16 patients showed that the mutation rates of PIM1, MYD88, KMT2D, TP53, CARD11, CCND3 and GNA13 were all > 20%, and TP53 mutation was associated with poorer PFS and OS ( P values 0.012 and 0.002). Conclusions:Female genital tract DLBCL is a rare invasive extranodal DLBCL with similar survival prognosis in primary and secondary patients. High-frequency mutations of PIM1, MYD88 and TP53 genes may provide new directions for treatment.

Intensive phototherapy vs. exchange transfusion for the treatment of neonatal hyperbilirubinemia: a multicenter retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia.@*METHODS@#This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years.@*RESULTS@#A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group.@*CONCLUSIONS@#In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.

Identification of the New Psychoactive Substance Eutylone / 法医学杂志

OBJECTIVES@#To establish a method to identify unknown sample based on the combined use of Fourier transform infrared spectroscopy (FTIR), gas chromatography-quadrupole time-of-flight mass spectrometry (GC-QTOF-MS), ultra-high performance liquid chromatography-linear ion trap quadrupole-orbitrap mass spectrometry (UPLC-LTQ-Orbitrap MS) and 1H-nuclear magnetic resonance spectroscopy (1H-NMR) technique.@*METHODS@#The unknown sample was directly analyzed by FTIR. The unknown sample was dissolved in methanol solution containing internal standard SKF525A and the supernatant was detected by GC-QTOF-MS and UPLC-LTQ-Orbitrap MS. The unknown sample was dissolved in methanol-d4 solution for structural analysis of 1H-NMR.@*RESULTS@#The characteristic absorption peaks of FTIR spectra obtained from unknown sample were 1 682 (C=O bond), 1 503, 1 488, 1 436, 1 363, 1 256, 1 092, 1 035, 935, 840 and 800 cm-1, the characteristic fragment ions (m/z) of GC-QTOF-MS were 86.096 4 (base peak), 58.065 1, 149.023 5, 121.028 6 and 65.038 6, the accurate mass [M+H]+ detected by UPLC-LTQ-Orbitrap MS was 236.127 7. The sample was identified as synthetic cathinone new psychoactive substance Eutylone by 1H-NMR.@*CONCLUSIONS@#The method established in this study can be used for structural confirmation of Eutylone.

Changes of cytokine levels before and after anti-tuberculosis treatment / 中国热带医学

@#Abstract： Objective　To analyze the changes of cytokine levels in patients with sensitive pulmonary tuberculosis and drug-resistant pulmonary tuberculosis before and after anti-tuberculosis treatment. Methods　The clinical data of 213 pulmonary tuberculosis patients admitted to the Eighth Affiliated Hospital of Xinjiang Medical University from August 2019 to October 2020 were collected, and divided into a sensitive pulmonary tuberculosis group and a drug-resistant pulmonary tuberculosis group, of which 141 were in the sensitive group and 72 in the drug-resistant group , and the pro-inflammatory factors tumor necrosis factor-α (TNF-α), IL-6, IL-17, interferon-γ (IFN-γ) and anti-inflammatory factors IL-10 and IL-4 in plasma before treatment, 3 months and 6 months after treatment were compared. Results　Compared with the healthy group, the levels of plasma IL-6 in the sensitive group and the resistant group were significantly increased, difference was statistically significant (P<0.01). The plasma levels of IFN-γ and IL-17 in the sensitive group were increased, and the difference was statistically significant (P<0.05). Compared with before treatment, the levels of IL-6 and IL-4 in the plasma of the sensitive group after 6 months of treatment were lower than those after 3 months of treatment, and the difference was statistically significant (P<0.05), and IFN-γ was significantly decreased (P<0.001). After 6 months of treatment, the IL-10 content was lower than that before treatment, and the difference was statistically significant (P<0.05), and the IFN-γ decreased significantly (P<0.000 1). The levels of IFN-γ at 3 months were higher than those in the resistant group, and the difference was statistically significant (P<0.01). After 6 months of treatment, there was no significant difference in the content of IFN-γ between the sensitive group and the resistant group. The effective rate of CT absorption was 70% in the sensitive group and only 43.33% in the resistant group at 3 months of treatment, and there was no significant difference in the effective rate between the two groups after 6 months of treatment. Conclusions　Detection of pro-inflammatory cytokines and anti-inflammatory cytokines in plasma can provide reference for host-directed therapy of pulmonary tuberculosis. Understanding this important feature of cytokines on pathogen-host interactions can provide new insights into the study of virulence mechanisms and may provide new approaches for immune intervention in pulmonary tuberculosis.

Research Advance in Treatment of Thrombotic Thrombocytopenic Purpura --Review / 中国实验血液学杂志

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, in which a severe deficiency of von Willebrand factor lyase results in thrombocytopenic clots that block blood vessels and eventually lead to terminal organ failure. Therapeutic plasma exchange is the cornerstone of TTP treatment which can greatly improves the survival rate of the patients. With the further exploration to the pathophysiological mechanism of TTP, other alternative therapies, new immunosuppressive agents, targeted antagonists, gene therapy and other emerging means gradually emerge, which are expected to further reduce the mortality and recurrence rate of the patients. In this review, the new developments in TTP treatment were summarized briefly.

The effect of diabetes mellitus in the elderly on memory function in patients with mild cognitive impairment / 中华老年医学杂志

Objective:To investigate the effect of diabetes mellitus in the elderly on memory function in patients with mild cognitive impairment(MCI).Methods:Totally 449 community residents were selected for a 2-year follow-up survey.Montreal Cognitive Assessment(MoCA)and Mini-Mental State Examination(MMSE)were selected for overall cognitive function assessment.Fuld Object Memory(FOM)and Digital Span Test(DST)were used to evaluate delayed recall and instantaneous memory.Demographic data such as gender, age, education level, marital history, annual income, blood pressure, medical history etc.were collected.The glycosylated hemoglobin, fasting insulin, and carotid artery intima-media thickness were checked regularly.All subjects were grouped into non-diabetes mellitus normal cognitive group(NDM-NC group), non-diabetes mellitus mild cognitive impairment group(NDM-MCI group), diabetes mellitus normal cognitive group(DM-NC group)and diabetes mellitus mild cognitive impairment group(DM-MCI group).Results:In cross-sectional observation, the first, second, and last recall scores in the FOM showed a decreasing trend in the DM-MCI group, showed a word "U" -shaped fluctuation trend in the DM-NC group and the NDM-MCI group, and showed no significant change in the NDM-NC group.There were no significant differences in DST anterior-backward test scores between the DM-MCI group and NDM-MCI group(all P>0.05).Through longitudinal follow-up and two-by-two comparison with the other three groups, the average value of glycosylated hemoglobin in the DM-MCI group(6.78±0.60)% was the highest, and the differences were statistically significant( P<0.05).During follow-up, the average carotid intima-media thickness(CIMT)was higher in the DM-MCI group(1.03±0.20)mm than in NDM-NC group(0.89±0.20)mm( P<0.05), and the difference was statistically significant.Comparing with the other three longitudinal follow-up groups, the CIMT thickening speed in DM-MCI group was fastest. Conclusions:Elderly DM patient population have a higher prevalence of MCI, and their memory function fluctuates or declines significantly.Therefore, regular detection of memory function is conducive to delaying the progression of DM and MCI.