Vancomycin-Loaded Sol-Gel System for In Situ Coating of Artificial Bone to Prevent Surgical Site Infections.

Surgical site infections (SSIs) related to implants have always been a major challenge for clinical doctors and patients. Clinically, doctors may directly apply antibiotics into the wound to prevent SSIs. However, this strategy is strongly associated with experience of doctors on the amount and the location of antibiotics. Herein, an in situ constructable sol-gel system is developed containing antibiotics during surgical process and validated the efficacy against SSIs in beagles. The system involves chitosan (CS), ß-glycerophosphate (ß-GP) and vancomycin (VAN), which can be adsorbed onto porous hydroxyapatite (HA) and form VAN-CS/ß-GP@HA hydrogel in a short time. The VAN concentration from VAN-CS/ß-GP@HA hydrogel is higher than minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) at the 21st day in vitro. In an in vivo canine model for the prevention of SSIs in the femoral condyle, VAN-CS/ß-GP@HA exhibits excellent biocompatibility, antimicrobial properties, and promotion of bone healing. In all, the CS/ß-GP instant sol-gel system is able to in situ encapsulate antibiotics and adhere on artificial bone implants during the surgery, effectively preventing SSIs related to implants.

Analysis of clinicopathological features, therapeutic efficacy, prognosis and mutation in 11 patients with cardiac diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the clinicopathological features, mutation, therapeutic efficacy and the factors influencing the prognosis of patients with cardiac diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 11 cardiac DLBCL patients in Ruijin Hospital of Shanghai Jiao Tong University School of Medicine from January 2016 to October 2020 were retrospectively analyzed. NovaSeq sequencing platform was used to detect gene mutations in 5 patients, and bioinformatics analysis of sequencing data was conducted through public database to identify the mutation sites of pathogenic genes. Kaplan-Meier method was used to analyze the progression-free survival (PFS) and the overall survival (OS). Univariate Cox proportional risk model was used to analyze the influencing factors of prognosis.Results:Among 11 patients with cardiac DLBCL, 5 were male and 6 were female. The age [ M ( Q1, Q3)] was 61 years (45 years, 70 years). All 11 patients were non-germinal center B-cell (non-GCB) type. There were 2 primary cases and 9 secondary cases; 9 cases with Ann Arbor stage of Ⅲ-Ⅳ, 10 cases with increased lactate dehydrogenase (LDH) and 9 cases with international prognostic index (IPI) score equal to or higher than 3 scores. Among 11 patients, 9 cases received a first-line treatment based on the R-CHOP (rituximab, cyclophosphamide, epirubicin/doxorubicin hydrochloride liposomes, vincristine and prednisone) regimen, of which 8 patients achieved complete remission (CR), and 1 patient achieved stable disease (SD); 1 patient received IR2 (ibrutinib + rituximab + lenalidomide) treatment regimen and achieved SD, and 1 patient received supportive treatment only and achieved progression of the disease. The follow-up time was 39.9 months (25.6 months, 57.3 months). The 3-year PFS rate and 3-year OS rate of 11 patients was 54.5%, 77.9 %, respectively. Univariate Cox regression analysis showed that gender, B symptoms, Ann Arbor stage, LDH level, number of extranodal lesions, IPI score were not correlated with PFS and OS of patients (all P > 0.05). Among 5 cases undergoing gene detection, KMT2D mutations and PIM1 mutations were detected in 2 cases,respectively. Interestingly, KMT2D mutations were only found in secondary cardiac DLBCL patients (2/3), while PIM1 mutations were only detected in primary cardiac DLBCL patients (2/2). Conclusions:Most cardiac DLBCL patients are non-GCB type and have advanced clinical stage, while may benefit from R-CHOP treatment regimen. PIM1 and KMT2D are the commonly mutated genes in cardiac DLBCL.

Clinical pathology and prognostic differences of primary CD5+diffuse large B cell lymphoma / 临床与实验病理学杂志

Purpose To explore the clinicopathological features and molecular characteristics of primary CD5+diffuse large B cell lymphoma(DLBCL).Methods Immunohisto-chemistry and next-generation sequencing(NGS)were used to compare the pathological features,immunophenotypes,and mo-lecular characteristics between primary CD5+DLBCL and CD5-DLBCL,and to analyze their relationship with prognosis and clinical characteristics of patients.Results Among 311 DLBCL patients,there were 46 cases(14.7％)of CD5+DLBCL.There were no statistically significant differences in patient gen-der,clinical staging,international prognostic index between CD5+DLBCL and CD5-DLBCL,and between CD5+DLBCL with and without MYD88 L265P mutation(P＞0.05).Immuno-phenotypically,the overexpression of BCL2(69.5％vs 49.4％,P=0.003)and the co-expression of BCL2 and C-MYC(26％vs 14％,P=0.04)were higher in the CD5+DLBCL group than those in the CD5-DLBCL group;the expression of C-MYC(53％vs 20％),BCL6(93.3％vs 61.3％),Ki67(93.3％vs 64.5％),and co-expression(46.7％vs 20.8％)were higher in the CD5+with MYD88 L265P mutation group than those in the CD5+without MYD88 L265P mutation group(P＜0.05).Survival analysis showed that the disease progres-sion-free survival time of patients in the CD5+DLBCL group tended to be shorter than that of patients in the CD5-DLBCL group(P=0.09).Furthermore,the disease progression-free survival time of patients in the CD5+without MYD88 L265P mutation group was significantly longer than that of patients in the CD5+with MYD88 L265P mutation group(P=0.04).NGS detection found differences in the distribution of accompan-ying mutated genes between CD5+DLBCL and CD5-DLBCL groups.ConclusionCD5 expression and CD5+with MYD88 L265P mutation may be potential indicators of poor prognosis in DLBCL patients.

Imaging study on thoracic and lumbar physiological curvature in adolescent idiopathic scoliosis / 中国骨伤

OBJECTIVE@#To observe the alteration of thoracic and lumbar physiological curvature in adolescent idiopathic scoliosis(AIS) and the difference of physiological curvature between different types of scoliosis.@*METHODS@#A retrospective analysis was conducted on 305 adolescent patients taken full spine X-ray in our hospital from January 2017 to December 2021. The patients were divided into normal group and scoliosis group. The normal group was composed of 179 patients, 79 males and 100 females, aged 10 to 18 years old with an average of (12.84±2.10) years old, with cobb agle less than 10 degrees. The scoliosis group was composed of 126 patients, 33 males and 93 females, aged 10 to 18 years old with an average of (13.92±2.20) years old. The gender, age, Risser sign, thoracic kyphosis(TK) and lumbar lordosis(LL) in 2 groups were compared, and the TK and LL were also compared between different genders, different degrees of scoliosis and different segments of scoliosis.@*RESULTS@#The female ratio(P=0.001) and age (P<0.001) in scoliosis group were higher than them in normal group; the ratio of low-grade ossification was higher in normal group than in scoliosis group(P=0.038). TK was significantly smaller in scoliosis group than in normal group(P<0.001), but there was no significant difference in LL between the 2 groups(P=0.147). There were no significant difference in TK and LL between male and female. The TK was significantly bigger in mild AIS patients than in moderate AIS patients(P<0.05), but there was no significant difference in LL between mild and moderate patients(P>0.05). The TK and LL in different segments scoliosis were not found significant difference.@*CONCLUSION@#The physiological curvature of thoracic and lumbar spine is independent of gender. The thoracic physiological curvature becomes smaller in AIS patients, but lumbar curvature remains unchanged. The thoracic physiological curvature in mild AIS patients is greater than that in moderate AIS patients, but the lumbar curvature is almost unchanged between mild and moderate scoliosis and is similar with that in normal adolescent. The alteration of thoracic and lumbar physiological curvature in AIS patients may be related to relative anterior spinal overgrowth, and the specific detailed mechanism needs to be further studied.

Clinicopathologic characteristics,gene mutation profile and prognostic analysis of thyroid diffuse large B-cell lymphoma / 上海交通大学学报（医学版）

Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of thyroid diffuse large B-cell lymphoma(DLBCL).Methods·From November 2003 to December 2021,a total of 66 patients with thyroid DLBCL[23 cases(34.8%)with primary thyroid DLBCL,and 43 cases(65.2%)with secondary thyroid DLBCL]admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival and prognostic factors.Gene mutation profiles were evaluated by targeted sequencing(55 lymphoma-related genes)in 40 patients.Results·Compared to primary thyroid DLBCL,secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ?Ⅳ(P=0.000),elevated serum lactate dehydrogenase(LDH)(P=0.043),number of affected extranodal involvement≥2(P=0.000),non-germinal center B cell(non-GCB)(P=0.030),BCL-2/MYC double expression(DE)(P=0.026),and international prognostic index(IPI)3?5-scores(P=0.000).The proportion of patients who underwent thyroid surgery(P=0.012)was lower than that of patients with primary thyroid DLBCL.The complete remission(CR)rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients(P=0.039).Fifty-five patients(83%)received rituximab combined with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)-based first-line regimen.The estimated 5-year progression free survival(PFS)rate of primary thyroid DLBCL patients was 95.0%,higher than the 49.7%of the secondary patients(P=0.010).Univariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.411,95%CI 1.373?14.170),elevated LDH(HR=5.500,95%CI 1.519?19.911),non-GCB(HR= 5.291,95%CI 1.667?16.788),and DE(HR=6.178,95%CI 1.813?21.058)were adverse prognostic factors of PFS in patients with thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ(HR=7.088,95%CI 0.827?60.717),elevated LDH(HR=6.982,95%CI 0.809?60.266),and DE(HR=18.079,95%CI 1.837?177.923)were adverse prognostic factors of overall survival(OS).Multivariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.693,95%CI 1.218?18.081)and elevated LDH(HR=5.058,95%CI 1.166?21.941)were independent adverse prognostic factors of PFS in patients with thyroid DLBCL.Targeted sequencing data showed mutation frequency>20%in TET2(n=14,35%),KMT2D(n=13,32%),TP53(n=11,28%),GNA13(n=10,25%),KMT2C(n=9,22%),and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL(P=0.000).Conclusion·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ,elevated LDH,non-GCB,and DE(MYC and BCL2)are adverse prognostic factors in thyroid DLBCL.TET2,KMT2D,TP53,GNA13,and KMT2C are commonly highly mutated genes in thyroid DLBCL,and the prognosis of patients with TP53 mutations is poor.

Application analysis of posture adaptation training combined with continuous passive exercise rehabili-tation in postoperative rehabilitation of patients undergoing coronary artery bypass grafting / 心血管康复医学杂志

Objective:To explore the application value of posture adaptation training combined with continuous pas-sive exercise rehabilitation for patients after coronary artery bypass grafting(CABG).Methods:A total of 100 pa-tients with coronary heart disease(CHD)undergoing CABG in our hospital were enrolled,divided into single group(n=50,received single continuous passive exercise rehabilitation intervention)and combined group(n=50,re-ceived posture adaptation training based on single group)according to color grouping method.Both groups were in-tervened for two months.Clinical indexes,cardiac function indexes,cognitive function,exercise endurance,serum levels of neuron specific enolase(NSE),S-100β protein and satisfaction were analyzed and compared between two groups.Results:Compared with single group after intervention,there were significant reductions in first out of bed time,first anal exhaust time and length of hospital stay,and significant rise in left ventricular ejection fraction(LVEF),cardiac index(CI),left ventricular fractional shortening(LVFS),score of Montreal cognitive assessment(MoCA)scale,6min walking distance,and significant reductions in serum levels of NSE[(19.93±1.90)μg/L vs.(16.59±2.25)μg/L]and S-100β protein[(6.72±0.34)μg/L vs.(3.96±0.19)μg/L]in combined group,P=0.001 all.Satisfaction in combined group was significantly higher than that of single group(94.00％vs.80.00％,P=0.037).Conclusion:Posture adaptation training combined with continuous passive exercise rehabilitation can sig-nificantly improve the clinical indexes,promote cardiopulmonary function and cognitive function recovery in pa-tients undergoing coronary artery bypass grafting after operation.

The three-connections and four-screwings technique via a single ilioinguinal approach for treatment of high double column acetabular fractures / 中华创伤骨科杂志

Objective:To investigate the clinical efficacy of three-connections and four-screwings technique in the treatment of high double column acetabular fractures through a single ilioinguinal approach.Methods:A retrospective study was conducted to analyze the data of 42 patients who had been treated for high double column acetabular fractures from June 2017 to June 2020 at Trauma Ward 2, Department of Orthopedics and Traumatology, The First Hospital of Traditional Chinese Medicine of Changde. There were 19 males and 23 females with an age of (42.7±25.6) years. 29 injuries were due to a traffic accident, 12 ones to fall from a height, and one to fall. The time from injury to operation was (4.5±2.1) days. All the patients were treated by the three-connections and four-screwings technique through a single ilioinguinal approach. Briefly, the anterior column was connected and secured to the main bone using 3 routes, and the posterior column was attached and fixated to the anterior column reset using 2 or 3 of the 4 screwings. The operation time, intraoperative blood loss, fracture reduction quality, fracture healing time, hip function at the last follow-up and complications during the follow-up were recorded.Results:For this cohort, the operation time was (150.0±30.5) min, and intraoperative blood loss (300.0±50.0) mL. According to the Matta scale for postoperative acetabular fracture reduction, 34 cases were excellent, 6 cases good, and 2 cases acceptable, with an excellent and good rate of 95.2% (40/42). After operation one patient had fat liquefaction and wound exudation which responded to drainage and dressing change. The 42 patients were followed up for (15.0±3.4) months. All fractures healed after (11.0±2.0) months. By the modified Merle d'Aubigné & Postel scoring system, the hip function was evaluated at the last follow-up as excellent in 33 cases, as good in 6 cases, and as fair in 3 cases, yielding an excellent and good rate of 92.9% (39/42).Conclusions:In the treatment of high double column acetabular fractures, the three-connections and four-screwings technique through a single ilioinguinal approach can lead to fine reduction and rigid fixation by lag screw compression and neutralization plate protection. Consequently, early functional exercises can be performed to secure good therapeutic outcomes for the patients.

A peptidic network antibody inhibits both angiogenesis and inflammatory response.

Corneal neovascularization (CNV) is a global threat to human health. Traditional anti-angiogenesis agent may have therapy effect, while the inflammation in disease area remains unsolved. Herein, we reported two binding-induced fibrillogenesis (BIF) peptides as peptidic network antibodies for high-efficient and long-lasting anti-angiogenesis with reduced inflammatory response. BIF peptides could self-assemble into nanoparticles and further perform BIF behavior through binding Ca2+. In vitro, the migration of integrin αvß3 highly expressed endothelial cells was inhibited by BIF peptides. In vivo, one BIF peptide (0.012 mg/Kg) exhibited higher anti-angiogenesis effect than monoclonal antibody bevacizumab (0.96 mg/Kg) in a CNV rabbit model on day 14, despite that the dose of BIF was only 1.3% of bevacizumab. Meanwhile, the inflammatory response, such as PI3 kinase/Akt pathway in CNV was successfully inhibited as well. The peptidic network antibody could block integrin αvß3 via a long-term retention mode, which led to long-term therapeutic effect. The study provides BIF peptides as promising therapeutic agents for both anti-angiogenesis and reduced inflammatory response.

Model-based joint curve registration and classification.

In this paper, we consider the problem of classification of misaligned multivariate functional data. We propose to use a model-based approach for the joint registration and classification of such data. The observed functional inputs are modeled as a functional nonlinear mixed effects model containing a nonlinear functional fixed effect constructed upon warping functions to account for curve alignment, and a nonlinear functional random effects component to address the variability among subjects. The warping functions are also modeled to accommodate common effect within groups and the variability between subjects. Then, a functional logistic regression model defined upon the representation of the aligned curves and scalar inputs is used to account for curve classification. EM-based algorithms are developed to perform maximum likelihood inference of the proposed models. The identifiability of the registration model and the asymptotical properties of the proposed method are established. The performance of the proposed procedure is illustrated via simulation studies and an analysis of a hyoid bone movement data application. The statistical developments proposed in this paper were motivated by the hyoid bone movement study, the methodology is designed and presented generality and can be applied to numerous areas of scientific research.

Identification and characterization of UDP-glycosyltransferase genes and the potential role in response to insecticides exposure in Bactrocera dorsalis.

BACKGROUND: The oriental fruit fly, Bactrocera dorsalis (Hendel) is a worldwide pest damaging a wide range of hosts. Due to the long-term indiscriminate use of insecticides, B. dorsalis has developed serious resistance to several insecticides. UDP-glycosyltransferases (UGTs) are secondary metabolic enzymes involved in biotransformation and play an important role in the metabolism of plant secondary metabolites and synthetic insecticides in insects. Thus, we suspect that UGTs in B. dorsalis play an important role in insecticide tolerance. RESULTS: In this study, 31 UGT genes were identified in the genome of B. dorsalis, belonging to 13 subfamilies. Real-time quantitative polymerase chain reaction (RT-qPCR) results revealed that 12 UGT genes were highly expressed in the antennae, midgut, Malpighian tubule and fat body. The mRNA expressions of 17 UGT genes were up-regulated upon exposure to λ-cyhalothrin, imidacloprid, abamectin and chlorpyrifos. Knockdown of the selected five UGT genes (BdUGT301D2, BdUGT35F2, BdUGT36K2, BdUGT49D2, BdUGT50B5) by RNA interference increased the mortality of B. dorsalis from 9.29% to 27.22% upon exposure to four insecticides. CONCLUSION: The abundance of UGTs in B. dorsalis is similar to other insect species, and 12 out of 31 UGTs were specifically expressed in metabolic tissues, suggesting a key role in detoxification. Down-regulation of five selected UGT genes increased the susceptibility of B. dorsalis to various insecticides, indicating that UGTs may play an important role in tolerance of B. dorsalis to multiple insecticides. © 2022 Society of Chemical Industry.

The In Vivo Intervention and Relative Mechanism of Genistein on the Inflammation and Thrombophilia in Lymphoma-Bearing Mice / 中国实验血液学杂志

OBJECTIVE@#To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice.@*METHODS@#Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX）drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice.@*RESULTS@#After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05).@*CONCLUSION@#Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.

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.

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.

Clinical features of fundus lesions of 74 patients with acquired immunodeficiency syndrome in Shenyang / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical features and factors of fundus lesions in patients with acquired immunodeficiency syndrome(AIDS)in Shenyang and the relationship between fundus lesions and CD4+T cell count.METHODS: Retrospective case study. A total of 74 cases with AIDS who were treated in the Central Hospital of Liaoning Electric Power Supply Co., Ltd., from January 2021 to December 2021 were selected. The fundus manifestation and CD4+T cell count of the patients were analyzed.RESULTS: The total detection rate of fundus lesions in AIDS patients was 58%. CD4+T cell count in the patients with fundus lesions was significantly lower than that in the patients with normal fundus [29(6, 55)/μL vs. 76(35, 103)/μL, P<0.01]. The rate of fundus lesions was the highest in the patients with CD4+T cell count ≤ 50/μL(74%). Logistic regression analysis showed that as the CD4+T cell count increased, the incidence of fundus lesions decreased(OR=0.977, 95%CI 0.964～0.991, P<0.01).CONCLUSION: Fundus lesions in AIDS patients related to CD4+T cell count. Decreasing CD4+T cell count was a risk factor of fundus lesions for AIDS patients. Routine fundus examination is important for the early diagnosis of fundus lesions in AIDS patients.

Biphasic Cholinergic Modulation of Reverberatory Activity in Neuronal Networks / 神经科学通报·英文版

Acetylcholine (ACh) is an important neuromodulator in various cognitive functions. However, it is unclear how ACh influences neural circuit dynamics by altering cellular properties. Here, we investigated how ACh influences reverberatory activity in cultured neuronal networks. We found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses, but to a much lesser extent at high doses. Moreover, high doses of ACh caused a longer duration of evoked reverberation, and a higher occurrence of spontaneous activity. With whole-cell recording from single neurons, we found that ACh inhibited excitatory postsynaptic currents (EPSCs) while elevating neuronal firing in a dose-dependent manner. Furthermore, all ACh-induced cellular and network changes were blocked by muscarinic, but not nicotinic receptor antagonists. With computational modeling, we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental observations. Thus, ACh modulates network dynamics in a biphasic fashion, probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.

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.

Comparative Study of Helicobacter pylori Infection Status in Tibetan and Chinese Families / 胃肠病学

Background:There is no comparison of the current status of Helicobacter pylori(Hp)infection in different ethnic groups in terms of families and their individuals.Aims:To investigated for the first time the status of Hp infection in Tibetan and Han Chinese families at the household level.Methods:A questionnaire was used to investigate factors associated with Hp in 50 Tibetan families in Ya'an,Sichuan Province,and 50 Han Chinese families in Chongqing Municipality.13C-urea breath test was used to detect Hp infection.Results:The individual and household Hp positivity rates of the Tibetan population in southwest China were 47.10%and 80%,which were significantly higher than those of the Han Chinese,which were 27.81%and 58%(P<0.05).However,the difference between Han and Tibetan in individual and household infection rates was not statistically significant.There are differences between Han Chinese and Tibetans in terms of infection status,geography,economic conditions,living habits and levels of hygiene.Infection was concentrated in certain family groups rather than being evenly distributed in the population.Conclusions:The current detection rate of Hp infection in individuals and families of Tibetan residents is significantly higher than that of Han Chinese,while the proportion of infected individuals is not statistically different.Transmission of Hp is characterized by family aggregation.There are differences in infection status,geographical environment,economic conditions,living habits and hygiene levels between Chinese and Tibetan families.

An intelligent peptide recognizes and traps Mycobacterium tuberculosis to inhibit macrophage phagocytosis.

Tuberculosis is a major public health concern worldwide, and it is a serious threat to human health for a long period. Macrophage phagocytosis of Mycobacterium tuberculosis (M. tuberculosis) is a crucial process for granuloma formation, which shelters the bacteria and gives them an opportunity for re-activation and spread. Herein, we report an intelligent anti-microbial peptide that can recognize and trap the M. tuberculosis, inhibiting the macrophage phagocytosis process. The peptide (Bis-Pyrene-KLVFF-WHSGTPH, in abbreviation as BFH) first self-assembles into nanoparticles, and then forms nanofibers upon recognizing and binding M. tuberculosis. Subsequently, BFH traps M. tuberculosis by the in situ formed nanofibrous networks and the trapped M. tuberculosis are unable to invade host cells (macrophages). The intelligent anti-microbial peptide can significantly inhibit the phagocytosis of M. tuberculosis by macrophages, thereby providing a favorable theoretical basis for inhibiting the formation of tuberculosis granulomas.