Diagnosis and management of orbital and cranial complications of pediatric acute rhinosinusitis / 中华耳鼻咽喉头颈外科杂志

Objective: To review the clinical characteristics, to illustrate diagnosis and management experience of orbital and cranial complications of pediatric acute rhinosinusitis. Methods: The clinical data of 24 children with orbital and cranial complications of acute rhinosinusitis who received endoscopic sinus surgery combined with drug treatment in Beijing Children's Hospital from January 2017 to December 2021 were retrospectively reviewed. There were 19 boys and 5 girls. The age varied from 13 to 159 months, with a median 47.5 months. The following diagnoses were obtained: 12 isolated subperiosteal orbital abscess, 2 associated with preseptal abscess, 2 associated with intraorbital abscess, 7 associated with optic neuritis, and 1 associated with septic cavernous sinus thrombosis. Clinical characteristics, organism isolated and outcomes were analyzed through descriptive methods. Results: All 24 patients presented with fever; 9 presented with nasal congestion and purulent discharge. The clinical manifestations of orbital infection included orbital edema, pain, proptosis and displacement of globe in all patients, while visual impairment was recognized in 7 children. Purulent drainage was cultured in 17 patients, among which 12 were positive. All patients underwent nasal endoscopic surgical interventions uneventfully, excluding one patient who required a second surgical procedure. Follow-up period ranged from 5 to 64 months. All patients resolved fully, with the exception of 2 children who got permanent blindness with visual loss preoperative. There was no recurrence or death. Conclusions: Orbital and cranial complications of pediatric acute rhinosinusitis could be severe with an occult onset. For patients with vison impairment, any signs of intracranial complications and a lack of response to conservative management, an urgent endoscopic intervention is needed.

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.

Determination of suspended erythrocyte volume range and establishment of its internal control standard / 中国输血杂志

【Objective】 To determine the volume range of suspended erythrocyte and establish its internal control standard. 【Methods】 The theoretical value of suspended erythrocyte volume was calculated according to the screening criteria of healthy blood donors and Quality Requirements for Whole Blood and Blood Components. A total of 2 410 bags of 1 U and 2 U suspended erythrocyte were randomly selected and weighed, and the volume range were formulated by ±2S and ±10% respectively and then compared to determine the volume range in line with the actual situation of our center. 【Results】 The theoretical volume range of 1 U and 2 U suspended erythrocyte were 117-160 mL vs 234-320 mL, and the actual volume range were 142-180 mL vs 276-393 mL. The volume range of 1 U and 2 U suspended erythrocyte formulated by ±2S were 145-181 mL vs 298-358 mL, and by ±10% were 147-179 mL vs 295-361 mL. The hematocrit and hemoglobin content of suspended erythrocyte within the actual volume range met the quality requirements. There were fluctuations in the volume of suspended erythrocyte from different regions. 【Conclusion】 Based on the actual situation of our center and the sampling results of suspended erythrocytes in recent two years, 163 mL±10% and 328 mL±10% were determined as the internal control standards of 1 U and 2 U suspended erythrocyte, respectively. Blood centers should establish accurate and feasible standard of suspended erythrocyte according to the actual situation.

A comparative study of the clinical characteristics of spotted fever and severe fever with thrombocytopenia syndrome / 中国热带医学

@#Abstract: Objective To investigate the differences in epidemiological and clinical characteristics of patients with spotted fever (SF) and severe fever with thrombocytopenia syndrome (SFTS). Methods A total of 86 patients with SF and 113 patients with SFTS who were laboratory-confirmed in the second-level and above hospitals in Lu'an City from January 2017 to January 2022 were selected. The basic data, epidemiological history, clinical data and laboratory test results of the two diseases were retrospectively analyzed for comparison. Results The proportion of male in SF group was 32.56% (28/86), and the proportion of male in SFTS group was 53.98% (61/113), the difference was statistically significant (χ2=9.067, P<0.01). The proportions of abdominal pain and diarrhea in the SF group were (3.49%, 3/83) and (21.24%, 24/113), which were significantly lower than corresponding (6.98%, 6/86) and (46.90%, 53/113) in the SFTS group (χ2=13.121, 37.322, P<0.01). The incidences of rash and eschar in SF group were 95.35% (82/86) and 20.93% (18/86), which were significantly higher than corresponding 1.77% (2/113) and 0.88% (1/113) in SFTS group (χ2=175.311, 22.721, P<0.01). The levels of leukocytes, platelets and C-reactive protein in the SF group were significantly higher than those in the SFTS group, and the levels of transaminase, lactate dehydrogenase and D-dimer were significantly lower than those in the SFTS group, and the differences were statistically significant (all P<0.05). Conclusions The rash and inflammatory reaction are more obvious in SF patients, while the liver function, myocardial function and coagulation function are significantly impaired in SFTS patients.

Evaluation of peripheral blood T-lymphocyte subpopulations features in patients with hepatitis B virus-related acute-on-chronic liver failure based on single-cell sequencing technology / 中华肝脏病杂志

Objective: T lymphocyte exhaustion is an important component of immune dysfunction. Therefore, exploring peripheral blood-exhausted T lymphocyte features in patients with hepatitis B virus-related acute-on-chronic liver failure may provide potential therapeutic target molecules for ACLF immune dysfunction. Methods: Six cases with HBV-ACLF and three healthy controls were selected for T-cell heterogeneity detection using the single-cell RNA sequencing method. In addition, exhausted T lymphocyte subpopulations were screened to analyze their gene expression features, and their developmental trajectories quasi-timing. An independent sample t-test was used to compare the samples between the two groups. Results: Peripheral blood T lymphocytes in HBV-ACLF patients had different differentiation trajectories with different features distinct into eight subpopulations. Among them, the CD4(+)TIGIT(+) subsets (P = 0.007) and CD8(+)LAG3(+) (P = 0.010) subsets with highly exhausted genes were significantly higher than those in healthy controls. Quasi-time analysis showed that CD4(+)TIGIT(+) and CD8(+)LAG3(+) subsets appeared in the late stage of T lymphocyte differentiation, suggesting the transition of T lymphocyte from naïve-effector-exhausted during ACLF pathogenesis. Conclusion: There is heterogeneity in peripheral blood T lymphocyte differentiation in patients with HBV-ACLF, and the number of exhausted T cells featured by CD4(+)TIGIT(+)T cell and CD8(+)LAG3(+) T cell subsets increases significantly, suggesting that T lymphocyte immune exhaustion is involved in the immune dysfunction of HBV-ACLF, thereby identifying potential effective target molecules for improving ACLF patients' immune function.

Re-discussion on the comprehensive treatment strategy of complex ventral hernia from the perspective of intraperitoneal pressure / 中华外科杂志

Complex ventral hernia refers to a large hernia that is complicated by a series of concurrent conditions. Change in intra-abdominal pressure is one of the main pathways through which various factors exert an impact on perioperative risk and postoperative recurrence. Taking abdominal pressure reconstruction as the core, the treatment strategy for complex abdominal hernia can be formulated from three aspects: improving patients' tolerance, expanding abdominal cavity volume, and reducing the volume of abdominal contents. Improving patients' tolerance includes abdominal wall compliance training and progressive preoperative pneumoperitoneum. To expand the volume of the abdominal cavity, implanting hernia repair materials, component separation technique, autologous tissue transplantation, component expend technique, and chemical component separation can be used. Initiative content reduction surgery and temporary abdominal closure may be performed to reduce the volume of abdominal contents. For different cases of complex ventral hernia, personalized treatment measures can be safely and feasibly adopted depending on the condition of the patients and the intra-abdominal pressure situation.

Clinical characteristics and prognosis of primary and secondary diffuse large B-cell lymphoma of the pancreas / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of primary and secondary pancreatic diffuse large B-cell lymphoma (DLBCL) . Methods: Clinical data of patients with pancreatic DLBCL admitted at Shanghai Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from April 2003 to June 2020 were analyzed. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes). Univariate and multivariate Cox regression models were used to evaluate the prognostic factors of overall survival (OS) and progression-free survival (PFS) . Results: Overall, 80 patients were included; 12 patients had primary pancreatic DLBCL (PPDLBCL), and 68 patients had secondary pancreatic DLBCL (SPDLBCL). Compared with those with PPDLBCL, patients with SPDLBCL had a higher number of affected extranodal sites (P<0.001) and had higher IPI scores (P=0.013). There was no significant difference in the OS (P=0.120) and PFS (P=0.067) between the two groups. Multivariate analysis indicated that IPI intermediate-high/high risk (P=0.025) and double expressor (DE) (P=0.017) were independent adverse prognostic factors of OS in patients with pancreatic DLBCL. IPI intermediate-high/high risk (P=0.021) was an independent adverse prognostic factor of PFS in patients with pancreatic DLBCL. Targeted sequencing of 29 patients showed that the mutation frequency of PIM1, SGK1, BTG2, FAS, MYC, and MYD88 in patients with pancreatic DLBCL were all >20%. PIM1 (P=0.006 for OS, P=0.032 for PFS) and MYD88 (P=0.001 for OS, P=0.017 for PFS) mutations were associated with poor OS and PFS in patients with SPDLBCL. Conclusion: There was no significant difference in the OS and PFS between patients with PPDLBCL and those with SPDLBCL. IPI intermediate-high/high risk and DE were adverse prognostic factors of pancreatic DLBCL. PIM1, SGK1, BTG2, FAS, MYC, and MYD88 were common mutations in pancreatic DLBCL. PIM1 and MYD88 mutations indicated worse prognosis.

Effect of diosgenin on mTOR/FASN/HIF-1α/VEGFA expression in rats with non-alcoholic fatty liver disease / 中国中药杂志

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.

Mechanism of heat-clearing prescriptions in alleviating type 2 diabetes mellitus:a review / 中国中药杂志

Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.

Detection and analysis of neutralizing antibodies against SARS-CoV-2 in convalescent plasma donors / 中国输血杂志

【Objective】 To detect the anti-SARS-CoV-2 neutralizing antibody levels in convalescent plasma (CP) and to evaluate whether it has specific anti-SARS-CoV-2 S antigen effect, so as to provide laboratory data support for clinical use of CP. 【Methods】 Nine CP donors who have recovered from COVID-19 were studied, and 4 volunteers who completed the vaccination and 3 asymptomatic infected blood donors were compared. Anti-SARS-CoV-2 antibodies including total antibody, IgM and IgG were measured by chemiluminescence microparticle immunoassays (CMIA) test in three groups. The VSV pseudovirus-based neutralization assay for evaluating neutralizing antibodies against SARS-CoV-2 was carried out in all samples. 【Results】 All samples were tested positive by the total antibody and IgG CMIA in COVID-19 CP donors and recipients of inactivated COVID-19 vaccine. High titers of IgG were observed in CP donors and vaccine recipients compared with asymptomatic blood donors. All vaccine recipients and 8 of 9 CP donors tested positive by SARS-CoV-2 pseudovirus-based neutralization test, whereas all asymptomatic blood donors tested negative. 【Conclusion】 The levels and characteristics of neutralizing antibodies among COVID-19 CP donors, vaccine recipients and asymptomatic blood donors were different. When unable to implement the pseudovirus assay to measure neutralizing antibodies, the detection of total antibody can be considered instead.

Determination of methylene blue release in plasma virus inactivation bag by fluorescence energy transfer method / 中国输血杂志

【Objective】 To establish a simple, economical and rapid method for the determination of methylene blue (MB) release in virus inactivation bag. 【Methods】 Based on the fluorescence energy transfer between MB and BSA-stabilized gold nanoclusters (BSA-AuNCs), the standard curve of MB determination was established by measuring the fluorescence quenching degree of MB to BSA-AuNCs in different concentrations to conduct the determination of MB release in virus inactivation bag. 【Results】 There was a good linear relationship between the MB concentration (cMB) and the fluorescence quenching degree of BSA-AuNCs[ (I0-I)/I0=0.018cMB+ 0.021(r=0.996)] when the fluorescence emission wavelength was about 620 nm and the cMB was in the range of (0.9-36) μmoL/L. The recovery of MB was 98.00% -101.95 % when applied to determine MB at high, medium, and low concentrations, the obtained intra-day variation coefficients were 0.73%, 0.81% and 0.77% respectively, and the obtained inter-day variation coefficients were 3.92%, 3.81%, and 4.73% respectively. There was no significant difference between the results measured by this method and those measured by combination of solid-phase extraction and spectrophotometry(P>0.05). 【Conclusion】 The fluorescence energy transfer method could achieve simple and rapid determination of MB release in virus inactivation bag with accurate and reliable results.

Determination of fibrinogen content in cryoprecipitated antihemophilic factor by fluorescence quenching method / 中国输血杂志

【Objective】 To establish a new method for the determination of fibrinogen content in cryoprecipitated antihemophilic factor. 【Methods】 Fibrinogen (Fib) could bind with sheep anti-human fibrinogen (anti-Fib) specifically and further form antigen-antibody complex. When the Fib was present in the solution, the fluorescence of fluorescein isothiocyanate (FITC) labeled on the anti-Fib (FITC-anti-Fib) was quenched due to the formation of immune complex. The fluorescence quenching degree of FITC-anti-Fib was positively correlated with Fib concentration (cFib) in a certain concentration range. 【Results】 The linear relationship between fluorescence quenching degree [(I0-I)/I0] of FITC-anti-Fib and ln(cFib) was (I0-I)/I0=15.53ln(cFib)+ 80.79 (R2=0.99) when the cFib was in the range of (0.007 8-0.560 0) g/L. The recovery of Fib was (96.77-102.43) %. When the method was applied to determine Fib at high, medium, and low concentrations, the obtained intra-day variation coefficients were 0.31%, 0.56%, and 0.49%, respectively, and the inter-day variation coefficients were 3.81%, 3.06%, and 4.13%, respectively. There was no significant difference between the results measured by fluorescence quenching method and coagulation method (t=-0.075, P>0.05). 【Conclusion】 In this work, a new fluorescence method for the determination of Fib in cryoprecipitated antihemophilic factor was successfully established based on the specific combination of fib and FITC-anti-Fib. The method is simple and rapid. The obtained results were accurate and reliable by using this method to determine Fib.

Inhibition of Ciliogenesis Enhances the Cellular Sensitivity to Temozolomide and Ionizing Radiation in Human Glioblastoma Cells / 生物医学与环境科学（英文）

Objective@#To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM).@*Methods@#GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay.@*Results@#Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation.@*Conclusion@#Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.

Prognostic factors of grade Ⅲ- Ⅳ mixed hemorrhoids with anorectal resting hypertension and the therapeutic effect of MMH / 国际外科学杂志

Objective:To investigate the effect of external dissection and internal ligation (MMH) in the treatment of grade Ⅲ to Ⅳ mixed hemorrhoids with anorectal resting hypertension and its prognostic risk factors.Methods:The clinical data of 48 patients with grade Ⅲ-Ⅳ mixed hemorrhoids complicated with rectal and anal resting hypertension treated by MMH in Nanjing Jiangbei people′s Hospital Affiliated to Nantong University from February 2018 to February 2020 were analyzed retrospectively (observation group), including 24 males and 24 females; The age ranged from 22 to 55 (41.87±7.52) years. Another 48 patients with grade Ⅲ-Ⅳ mixed hemorrhoids complicated with anorectal resting hypertension treated by PPH were selected as the control group, including 20 males and 28 females; The average age was (42.68±7.14) years. The clinical effective rates , pain score at 6, 24 and 72 h after operation, postoperative complications were compared between the two groups. Multiple logistic regression was used to analyze the related risk factors affecting the prognosis.Results:There was no significant difference in VAS score between the two groups at 6 h after operation ( t=0.25, P=0.807); the VAS score of the observation group at 24 h and 72 h after operation was lower than that of the control group ( t=7.044, P<0.001; t=5.307, P<0.001); the total effective rate of the observation group was higher than that of the control group (93.75% vs 77.08%, χ2=5.35, P=0.021); the total incidence of postoperative anal edema, defecation difficulty, bloody stool, anal pain and fecal incontinence in the observation group was lower than that in the control group, the difference was statistically significant (12.50% vs 33.33%, χ2=5.879, P=0.015). Age, course of disease, grading of internal hemorrhoids and treatment methods were related to the prognosis of patients ( P<0.05); logistic regression analysis showed that age (> 45 years), course of disease (>10 years), grade of internal hemorrhoids (grade Ⅳ) and treatment (PPH) were independent risk factors for prognosis of patients ( P<0.05). Conclusions:MMH has less complications, less postoperative pain and satisfactory curative effect in the treatment of Ⅲ to Ⅳ mixed hemorrhoids and anorectal resting hypertension. The older the patients, the longer the course of disease, the higher the degree of internal hemorrhoids and the choice of treatment methods were the risk factors for the prognosis. Early diagnosis and reasonable treatment are helpful to improve the prognosis of patients.

Inhibition of Toll-like receptor 4 pathway by TAK242 protects the liver in sepsis / 中华危重病急救医学

Objective:To investigate the protective mechanism of TAK242, a specific inhibitor of Toll-like receptor 4 (TLR4), on the liver of septic rats.Methods:Eighteen male Sprague-Dawley (SD) rats were randomly divided into three groups ( n = 6 in each group). The septic model was established by intraperitoneal injection of lipopolysaccharide (LPS) 15 mg/kg. The rats in the TAK242 intervention group received intraperitoneal injection of TAK242 (5 mg/kg) before modeling, while the rats in the septic model group and the control group were injected with the same amount of solvent [10% dimethyl sulfoxide (DMSO) + 90% corn oil]. Six hours later, the blood of abdominal aorta was collected and the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by enzyme linked immunosorbent assay (ELISA). The rats were sacrificed to obtain liver, the expression levels of TLR4, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cysteinyl aspartate-specific proteinase-3 (caspase-3), nuclear factor-κB p65 (NF-κB p65) and phosphorylated NF-κB p65 (p-NF-κB p65) were detected by Western blotting. Immunohistochemical staining was used to observe NF-κB p65 protein expression in liver, and hepatocyte injury was assessed by hematoxylin-eosin (HE) staining. Results:Serum ALT and AST levels in the septic model group were significantly higher than those in the control group [ALT (μg/L): 26.639±7.814 vs. 2.847±2.150, AST (μg/L): 28.442±8.417 vs. 5.779±3.019, both P < 0.01]. The ALT and AST levels in the TAK242 intervention group were significantly lower than those in septic model group [ALT (μg/L): 7.269±3.398 vs. 26.639±7.814, AST (μg/L): 3.580±3.115 vs. 28.442±8.417, both P < 0.01]. Light microscopy showed that the hepatocytes in the septic model group were disordered, with obvious cell edema and increased inflammatory cells infiltration; the hepatocytes in the TAK242 intervention group were more neatly arranged, with significantly reduced hepatocyte edema and reduced inflammatory cells infiltration. Western blotting results showed that caspase-3 protein expression in hepatic tissue of septic model group was significantly higher than that in the control group (caspase-3/GAPDH: 0.794±0.164 vs. 0.482±0.055, P < 0.05), and caspase-3 protein expression in the TAK242 intervention group significantly decreased than that in the septic model group (caspase-3/GAPDH: 0.482±0.056 vs. 0.794±0.164, P < 0.05), which indicated that TAK242 could attenuate hepatocytes apoptosis of septic rats. The expression of IL-6, TNF-α and TLR4 protein and the ratio of p-NF-κB p65/NF-κB p65 in hepatic tissue of septic model group were significantly higher than those in control group (IL-6/GAPDH: 1.442±0.204 vs. 1.019±0.024, TNF-α/GAPDH: 1.089±0.098 vs. 0.806±0.005, TLR4/GAPDH: 1.292±0.085 vs. 0.941±0.087, p-NF-κB p65/NF-κB p65 ratio: 1.936±0.081 vs. 1.579±0.183, all P < 0.05), IL-6, TNF-α and TLR4 protein expression and p-NF-κB p65/NF-κB p65 ratio in the TAK242 intervention group were significantly lower than those in septic model group (IL-6/GAPDH: 1.035±0.042 vs. 1.442±0.204, TNF-α/GAPDH: 0.572±0.096 vs. 1.089±0.098, TLR4/GAPDH: 0.984±0.078 vs. 1.292±0.085, p-NF-κB p65/NF-κB p65 ratio: 1.484±0.255 vs. 1.936±0.081, all P < 0.05), it is suggested that LPS-induced sepsis could activate the inflammatory response mediated by TLR4/NF-κB pathway in liver, and the activation of TLR4/NF-κB pathway was inhibited by TAK242 through the TLR4 pathway, therefore, the inflammation of liver in septic rats was reduced. Immunohistochemical staining showed that the positive expression of NF-κB p65 in liver was significantly increased in the septic model group compared with the control group; the positive expression of NF-κB p65 was significantly reduced in the TAK242 intervention group compared with the septic model group, and there was almost no positive expression in the nucleus. Conclusion:TAK242 could reduce liver function injury and protect the liver by inhibition TLR4/NF-κB pathway in septic rats.

Study on the changes of cellular immune function after endoscopic radiofrequency ablation in extrahepatic cholangiocarcinoma / 肿瘤研究与临床

Objective:To investigate the effect of radiofrequency ablation treatment of extrahepatic cholangiocarcinoma under endoscopic retrograde cholangiopancreatography on the cellular immune function of patients with extrahepatic cholangiocarcinoma.Methods:A prospective cohort study was conducted on 78 patients with inoperable extrahepatic cholangiocarcinoma who visited Shanxi Provincial People's Hospital from October 2019 to January 2022. All of 78 patients underwent endoscopic radiofrequency ablation. Peripheral venous blood was collected from all patients at 1 day before treatment, 1 week after treatment and 1 month after treatment. Lymphocyte subsets were detected by flow cytometry, and levels of cytokines were detected by enzyme-linked immunosorbent assay. Seventy-eight healthy subjects with the same age and gender as the patients were selected as healthy controls, and the same indicators were tested.Results:The patient's peripheral blood total bilirubin was (193±83) μmol/L at 1 day before treatment, and decreased to (55±49) μmol/L at 1 week after treatment ( t = 16.70, P < 0.001); γ-glutamyltransferase was (242±108) U/L at 1 day before treatment, and decreased to (92±70) U/L at 1 week after treatment ( t = 19.12, P < 0.001). The proportion of natural killer (NK) cells, CD3 + T cells, CD4 + T cells, ratio of CD4 + T cells to CD8 + T cells (CD4/CD8) and level of interferon γ (IFN-γ) of patients at 1 day before treatment were lower than those of healthy control group (all P < 0.05), the proportion of CD8 + T cells and regulatory T cells was higher than those of healthy control group (both P < 0.001), and there was no significant difference in the levels of interleukin 4 (IL-4) between the patients at 1 day before treatment and the healthy control group ( P = 0.545). At 1 week and 1 month after treatment, the proportion of NK cells, CD3 + T cells, CD4 + T cells, CD4/CD8 and IFN-γ level in patients increased compared with 1 day before treatment (all P < 0.001), and decreased at 1 month after treatment compared with 1 week after treatment (all P < 0.001). At 1 week and 1 month after treatment, the proportion of CD8 + T cells and IL-4 level in patients decreased compared with 1 day before treatment (both P < 0.001), and increased at 1 month after treatment compared with 1 week after treatment (both P < 0.001). At 1 week and 1 month after treatment, the proportion of regulatory T cells decreased compared with 1 day before treatment (both P < 0.001), and decreased at 1 month after treatment compared with 1 week after treatment ( P < 0.001). Conclusions:Patients with extrahepatic cholangiocarcinoma are at a low level of immunity. Endoscopic radiofrequency ablation treatment can alleviate the patient's immunosuppression, enhance the patient's cellular immunity.

Clinical Application of Zanubrutinib in B-Cell Lymphoma --Review / 中国实验血液学杂志

Zanubrutinib is a highly selective second-generation BTK inhibitor developed in China and first approved by the U.S. Food and Drug Administration (FDA) as a novel antineoplastic drug. In recent years, with the birth of molecularly targeted drugs, the treatment of B-cell lymphoma have entered the era of targeted therapy, and immunotherapy has been widely accepted. Especially in some relapsed and refractory lymphomas, zanubrutinib has shown deep and sustained remissions and a favorable safety, which lays a foundation for precision therapy. In this review the clinical application and new progress for zanubrutinib in B-cell lymphoma was summarized briefly.

The effects of exercise on the renin-angiotensin system in blood and skeletal muscle after heart failure / 中华物理医学与康复杂志

Objective:To observe the effect of exercise on the renin-angiotensin system (RAS) in the blood and skeletal muscles of rats with chronic heart failure (CHF).Methods:Fifty male Wistar rats were randomly divided into a sedentary control group, an exercise control group, a model sedentary group and a model exercise group. CHF was modelled in the rats of the model sedentary and exercise groups, while those of the sedentary and exercise control groups received a sham operation. The exercise groups performed treadmill exercise for 8 weeks (5 times per week). After the 8 weeks the activity of angiotensin-converting enzyme (ACE) and ACE2 in the plasma and soleus muscle was determined using the fluorescent substrate method. Angiotensin II (AngII) and Ang (1-7) were detected in plasma and the soleus muscle using liquid chromatography. The expression of Ang II type 1 receptor (AT1R) and Mas receptor (MasR) in skeletal muscles was detected using western blotting.Results:Compared with the sedentary control group, there was significantly increased average ACE activity and lower average ACE2 activity in the model sedentary group. There was a significant decrease in the average plasma Ang II content and ACE activity, and a significant increase in the Ang-(1-7)/Ang II ratio in the model exercise group. Compared with the model sedentary group, the average ACE activity and plasma Ang II content was significantly lower in the model exercise group but the average ACE2 activity was significantly higher. Compared with the sedentary control group, the average Ang II content and AT1R protein expression in the soleus muscles had increased significantly in the model sedentary group, and the average expression of MasR protein in the soleus muscles increased significantly in the model exercise group. However, compared with the model sedentary group, the average content of Ang II and the average expression of AT1R protein in the soleus muscles had decreased significantly in the model exercise group and the average Ang-(1-7)/Ang II ratio had increased significantly.Conclusion:Exercise can induce the conversion of RAS from ACE-Ang II-AT1R to ACE2-Ang-(1-7)-MasR after chronic heart failure, at least in rats. The changes in the components of the RAS in the plasma and skeletal muscle differ.

Comparative study of two endovascular treatment strategies for isolated superior mesenteric artery dissection / 中华放射学杂志

Objective:To investigate the efficacy of bare stent implantation alone and stent assisted coiling in the repair of isolated superior mesenteric artery dissection (ISMAD) false lumen.Methods:Clinical data of 50 patients with ISMAD who underwent endovascular treatment between December 2012 and March 2021 were analyzed retrospectively. Depending on the endoluminal treatment methods, they were divided into the bare stent implantation alone group (29 cases) and the stent assisted coiling group (21 cases), and the rates of complete postoperative dissection remodeling, stent restenosis, and symptom recurrence were compared between the two groups.Results:The rates of complete remodeling of the dissection in the immediate postoperative period, 3 months and 6 months in the bare stent placement alone group were 13.8% (4/29), 51.7% (15/29) and 75.9% (22/29), respectively, which were lower than that of the stent assisted coiling group 71.4% (15/21), 85.7% (18/21), and 100% (21/21), and the difference was statistically significant (χ 2=17.17, 6.27, 4.06 respectively, and P=0.001, 0.012, 0.044 respectively). While the rates of complete remodeling of the dissection were 82.8%(24/29), 100%(21/21) in the two groups at 12 months after surgery, respectively, and the difference was not statistically significant (χ 2=2.34, P=0.126). There was no significant difference in stent patency rate and symptom recurrence rate between the two groups ( P>0.05). Conclusions:The efficacy of bare stent implantation alone and stent assisted coiling in the treatment of ISMAD is definite. Although the rate of complete remodeling of the dissection with bare stent placement alone is low in the short term, the rate of complete remodeling of the dissection with bare stent implantation alone gradually increases with the extension of time, which is worthy of clinical application and promotion.

The processing of blood with irregular antibodies and its clinical application / 中国输血杂志

【Objective】 Toexplore the viability of preparing washed RBCs ordeglycerolized RBCs(referred as frozen RBCs)from blood containing irregular antibodies, so as to provide references for formulating processing procedures of blood containing irregular antibodiestosave blood resources and reduce blood wastage. 【Methods】 Once irregular antibodies were yielded, their type and titerwere determined.The plasma was discarded, and the suspended RBCs were prepared and processed according to the standardized washing scheme.The processing effect of blood with different titers and types of antibodies was observed, and theirfurther clinical application was followed up. 【Results】 From May 2017 to July 2019, a total of 45 blood samples containing irregular antibodies were screened in our center. The overall qualified rate reached 91.1% after processing. 100%(25/25) was qualified in IgM, and 80.0%(16/20)in IgG.4samples, initially noncom for mingdue to IgG-Dwith titerranged8~16, met the requirements after one or two additional washing processes. Among them, 23 cases were issued and appliedin clinicaland noadeverse reactions to blood transfusionoccurred. 【Conclusion】 After appropriate processing, blood containing irregular antibody can be applied to the clinical to save blood resources. When the irregular antibody is IgG-D and the titer is high, the washing times should be increased, and only when there is no residual antibodycan the samples be issued to the clinical.