Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases / 中华病理学杂志

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

Construction of a caries diagnosis model based on microbiome novelty score / 华西口腔医学杂志

OBJECTIVES@#This study aimed to analyze the bacteria in dental caries and establish an optimized dental-ca-ries diagnosis model based on 16S ribosomal RNA (rRNA) data of oral flora.@*METHODS@#We searched the public databa-ses of microbiomes including NCBI, MG-RAST, EMBL-EBI, and QIITA and collected data involved in the relevant research on human oral microbiomes worldwide. The samples in the caries dataset (1 703) were compared with healthy ones (20 540) by using the microbial search engine (MSE) to obtain the microbiome novelty score (MNS) and construct a caries diagnosis model based on this index. Nonparametric multivariate ANOVA was used to analyze and compare the impact of different host factors on the oral flora MNS, and the model was optimized by controlling related factors. Finally, the effect of the model was evaluated by receiver operating characteristic (ROC) curve analysis.@*RESULTS@#1) The oral microbiota distribution obviously differed among people with various oral-health statuses, and the species richness and species diversity index decreased. 2) ROC curve was used to evaluate the caries data set, and the area under ROC curve was AUC=0.67. 3) Among the five hosts' factors including caries status, country, age, decayed missing filled tooth (DMFT) indices, and sampling site displayed the strongest effect on MNS of samples (P=0.001). 4) The AUC of the model was 0.87, 0.74, 0.74, and 0.75 in high caries, medium caries, low caries samples in Chinese children, and mixed dental plaque samples after controlling host factors, respectively.@*CONCLUSIONS@#The model based on the analysis of 16S rRNA data of oral flora had good diagnostic efficiency.

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.

Mechanism of racanisodamine on alleviating radiation-induced lung injury in mice / 中华放射医学与防护杂志

Objective:To investigate the protective effect of racanisodamine on lung injury in mice exposed to irradiation.Methods:C57BL/6 mice were randomly divided into control group, racanisodamine group, 18 Gy irradiation group (model group) and racanisodamine combined with 18 Gy irradiation group (treatment group), with 5 mice in each group. The mice in the treatment group received racanisodamine (5 mg/kg) intraperitoneally 3 d before irradiation and contained the whole experiments. Then, single chest irradiation of 18 Gy X-rays was performed both in the model and treatment groups. The racanisodamine group and treatment group received racanisodamine intraperitoneally once a day until 6 weeks after irradiation. The mice were killed at 6 weeks after irradiation. The lung histopathology was observed by HE staining. Serum and bronchial alveolar lavage fluid (BALF) inflammatory cytokines such as TNF-α, IL-1β and IL-6 were determined by ELISA method. Cell senescence was detected by SA-β-Gal staining. The expressions of Nrf2, p-Nrf2 and p62 in lung tissue were performed by immunehistochemistry and Western blot assays.Results:Compared with the model group, the scores of HE staining were decreased ( t=8.66, P<0.01), the number of infiltrated inflammatory cells in BALF were decreased ( t=10.70, P<0.01), and protein concentration in BALF had lower levels ( t=6.75, P<0.01), the serum TNF-α, IL-1β and IL-6 were decreased significantly ( t=8.17, 4.58, 6.54, P<0.01), the activity of SA-β-gal was decreased, and the expressions of Nrf2, p-Nrf2 were enhanced ( t=6.42, 7.30, P<0.01), while the expression of p62 was reduced ( t=4.62, P<0.01) in the treatment group. Conclusions:Racanisodamine plays the protective effect of radiation-induced lung injury by alleviating inflammation associating with the activating of Nrf2-related pathway, which reversed radiation-induced cell senescence.

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.

Value of albumin RNAscope in situ hybridization in diagnosis and differential diagnosis of hepatocellular carcinoma / 中华病理学杂志

Objective: To investigate the utility of albumin RNAscope in situ hybridization in the diagnosis and differential diagnosis of hepatocellular carcinoma and its mimics. Methods: One hundred and fifty-two cases of hepatocellular carcinoma and its mimics and 33 cases of normal tissue were selected from the pathology database of the Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2019. Tissue microarrays were constructed and RNAscope in situ hybridization was performed to detect the expression of albumin mRNA. Results: No albumin mRNA expression was detected in normal tissues except for the liver. All hepatocellular carcinoma regardless of its degree of differentiation and primary or metastatic nature had detectable albumin mRNA, with strong and diffuse staining in 90.7% (49/54) of cases. While the positive rate of HepPar-1, Arg-1 or one of them by immunohistochemistry was 87.0% (47/54), 85.2% (46/54) and 92.6% (50/54) respectively. The positive rates of albumin mRNA in intrahepatic cholangiocarcinoma and biphenotypic hepatocellular carcinoma were 7/15 and 9/10, respectively. The former showed focal or heterogeneous staining, while the latter showed strong and diffuse staining. The positive rate of hepatoid adenocarcinoma was 8/19, and the albumin expression could be diffuse or focal. Sporadic cases of poorly differentiated gastric adenocarcinoma and metastatic colon adenocarcinoma showed focal staining of albumin mRNA. Conclusions: Detection of albumin mRNA by RNAscope in situ hybridization is of great value for the diagnosis and differential diagnosis of HCC, and the sensitivity may be improved by combining with HepPar-1 and Arg-1. It also offers different diagnostic clues according to different expression patterns.

Clinicopathological features and prognosis of high-grade B-cell lymphoma with MYC and bcl-2 and/or bcl-6 rearrangements / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics and prognosis of high-grade B-cell lymphoma (HGBL) involving combined rearrangements of MYC, bcl-2 and bcl-6. Methods: A total of 1 138 cases of large B cell lymphoma (LBL) that were treated at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2017 to September 2020 were analyzed using fluorescence in situ hybridization (FISH) with probes against MYC, bcl-2 and bcl-6. The clinical and pathological data of the 45 patients with HGBL that had rearrangements of MYC and bcl-2 and/or bcl-6 were collected and retrospectively analyzed. Results: Among the 1 138 LBL, 45 (4.0%) cases had combined rearrangements of MYC, bcl-2 and/or bcl-6 that included 6 HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, 14 HGBL cases with MYC and bcl-2 rearrangements, and 25 HGBL cases with MYC and bcl-6 rearrangements. Of these 45 patients, 29 patients were male, and 16 patients were female, aged 29 to 83 years. HGBL with MYC, bcl-2 and bcl-6 rearrangements and HGBL with MYC and bcl-2 rearrangement were reclassified as the germinal center B-cell (GCB) subtype using the Hans algorithm. HGBL with MYC and bcl-6 rearrangement were reclassified as the GCB subtype (68.0%) and the non-GCB subtype (32.0%). The vast majority of HGBL cases had a high Ki-67 proliferation index. Most HGBL patients had advanced stage disease with a high IPI score and an increased LDH level. Also, some patients had clinical features including elevated plasma β2-microglobulin levels, B symptoms, and bone marrow involvement. The IPI scores and LDH levels were significantly different between the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements and the HGBL cases with MYC and bcl-6 rearrangements (P<0.05). Compared with the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the HGBL cases with MYC and bcl-2 or bcl-6 rearrangements had a lower incidence of bone marrow involvement (P<0.05). There were no significant differences in the prognosis among HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the cases with MYC and bcl-2 rearrangements, and the cases with MYC and bcl-6 rearrangements (P>0.05). Conclusions: HGBL with MYC, bcl-2 and/or bcl-6 rearrangements are rare types of B-cell lymphoma with high degree of malignancy and have a short overall survival. To reduce misdiagnosis and improve diagnostic accuracy, it is necessary to assess the patients' clinical features and conduct histopathological, immunohistochemical and FISH analyses.

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.

Histopathological and MRI characteristics of facial unidentified filling objects / 中华医学美学美容杂志

Objective:Unidentified filling objects (UFO) can cause adverse results including infections, overfilling, asymmetry, foreign body granulomas, dislocation or psychological panic. To remove UFO accurately, it is important to locate and identify the injected substances preoperatively. This study investigated the viability of using MRI to correctly locate and identify injected substances by relating MRI to gross and pathological microscopic examination.Methods:Eighty-two facial UFO patients from 2013 to 2017 were studied by the experts of the Department of Image, Xinhua Hospital of Dalian University. Five of the patients were male and seventy-seven were female. The age ranged from 17 to 58 years with average 29.4 years. They came to our hospital for removal of UFO after they had facial injective fillers in the illegal medial offices. The injected sites involved in the forehead, temple, malar, cheek, nose, nasolabial folds, and chin. All the patients＇ faces were examined with MRI preoperatively, using T1W, T2W and fat-suppressed sequences. Based on the guides of MRI, UFOs were removed with their capsules by open approach. Samples were recorded with digital pictures and then were fixed in 10% formalin solution for microscopic examination of HE stained slices.Results:Based on MRI, gross and microscopic examination, UFO were classified into 3 types, gel-like fillers, solid particles, and growth factors. Gel-like fillers appeared strongly hyperintense on T2 W and STIR sequences and hypointense on T1 W sequences. Grossly, they looked like gruel covered by altered soft tissue. Under the light microscope, many pieces of blue-stained material were dispersed in subcutaneous tissue infiltrated with a large number of mononuclear cells and foreign-body giant cells. Solid particles had low to intermediate signal intensity on T1 W and T2 W images. Grossly, they were like sand merging in soft tissue. The biopsy showed crowed bubbles surrounded by tissue filled with a large number of mononuclear cells and foreign-body giant cells. For growth factors affected tissue, it was hard to differentiate between normal and abnormal on MRI. The affected tissue appeared as somehow hypointense on T1 W sequences and hyperintense on T2 W fat suppressed sequences. During the operation, the affected region was easy bleeding and full of fibrofatty tissue. Under the microscope, there were increased small blood vessels and collagens.Conclusions:Based on MRI, gross and microscopic examination, UFO can be classified into 3 types, gel-like fillers, solid particles, and growth factors. MRI is very important for doctors to assess the patient＇s conditions and make the plan of operation. MRI is also useful for doctors to locate UFO and understand the relationship between UFO and their nearby organs.

The role and mechanism of miRNA in STZ-induced mouse diabetic hepatopathy / 西安交通大学学报(医学版)

【Objective】 To reveal possible mechanisms of miRNA in diabetic hepatopathy through bioinformatics method. 【Methods】 Subset data of miRNA and their matched mRNAs in the liver of STZ-induced diabetic mice and the normal liver tissues of congenial mice by detecting on microarrays were collected from GEO database； information from the database and bioinformatics analysis were applied to mine a batch of miRNAs in diabetic hepatopathy and targeted mRNAs regulated. Then qRT-PCR was used to verify the expressions of miRNAs in diabetic liver from 20 STZ-treated Kunming mice and 10 normal homologous mice. 【Results】 Via detection and analysis， miRNAs differentially expressed （including 96 up-regulated and 77 down-regulated） were significantly obtained. Groups of miRNAs and their effectors （mRNAs） that may be related to the pathological process of diabetic liver disease in mice were screened by GO and KEGG enrichment analyses， combined with relevant protein annotations in the databases and references. The expressions of miR-200a-3p， miR-200b-3p and miR-222-3p in the mice’s liver tissue detected by qRT-PCR were significantly down-regulated. In addition， the expressions of related effector genes CERS6， MYBL1， SCD2， SLCO1A4 and PLK2 were up-regulated， while the expressions of ACSS2， BCL6 and SLC10A2 were down-regulated. 【Conclusion】 The variation trend of those candidate miRNAs in mouse diabetic liver compared with that in control livers was consistent with that of the previous studies and prediction， which revealed their potential molecular regulation in this disease process.

The Auxiliary Diagnostic Value of Serum Adenosine Deaminase in Acute Leukemia at Clinical Test / 中国实验血液学杂志

OBJECTIVE@#To investigate the auxiliary diagnostic value of serum adenosine deaminase (ADA) in acute leukemia (AL) at clinical test.@*METHODS@#123 AL patients hospitalized in Zhejiang hospital from November 2018 to March 2020 were enrolled as the observation group, and 98 healthy people in the same period were randomly enrolled as the control group. AL patients were divided into two groups: 77 acute myeloid leukemia (AML) patients for AML group and 46 acute lymphoblastic leukemia (ALL) patients for ALL group. The levels of adenosine deaminase (ADA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) and homocysteine (Hcy) in serum of the patients were detected, and the correlation of ADA with these items was analyzed. Receiver operating characteristic curve (ROC) was used to analyze the clinical diagnostic value of ADA, Yoden index was used to confirm the best cut-off point.@*RESULTS@#The serum ADA level in AL patients was significant higher than that in control group (P < 0.05). The results of Pearson correlation analysis showed that there was a significant positive correlation of ADA with Hcy, ALT, AST, GGT, LDH in AML group (r = 0.47, r = 0.28, r = 0.37, r = 0.22, r = 0.55); and also there was a significant positive correlation of ADA with GGT in ALL group (r = 0.54). In AML group, the maximum area under ROC curve was 0.761 (P = 0.00), 95% confidence interval was 0.682-0.841, sensitivity was 54.50%, specificity was 98.90%, and the best cut-off point was 17.1 U/L. In ALL group, the maximum area under ROC curve was 0.785, 95% confidence interval was 0.694-0.877, sensitivity was 65.90%, specificity was 84.00%, and the best cut-off point was 13.45 U/L.@*CONCLUSION@#The detection of ADA in serum can be used as an auxiliary examination in patients with AL, which can provide a certain value for the diagnosis of the disease.

Safety and efficacy of adjuvant chemotherapy with oxaliplatin and S-1 for patients with locally advanced gastric cancer after D2 lymph nodes dissection / 中华胃肠外科杂志

Objective: To investigate the safety and efficacy of oxaliplatin combined with S-1 (SOX) as adjuvant chemotherapy after D2 radical gastrectomy for locally advanced gastric cancer. Methods: A descriptive case series study was applied. Case inclusion criteria: (1) locally advanced gastric cancer confirmed by endoscopic biopsy or surgical specimen pathology as gastric adenocarcinoma; (2) receiving D2 radical gastric resection followed by SOX regimen adjuvant chemotherapy. Case exclusion criteria: (1) postoperative pathological TNM stage I or IV; (2) acute complications and emergency surgeries; (3) receiving neoadjuvant therapy; (4) concurrent malignancies and complications compromising patients' treatment or survival; (5) without receiving adjuvant SOX chemotherapy. A total of 94 patients with stage II-III gastric cancer who underwent D2 radical gastrectomy and postoperative adjuvant SOX chemotherapy at department of Gastrointestinal Surgery, Peking University People's Hospital from January 2014 to December 2019 were retrospectively enrolled. Chemotherapy-related adverse events, overall survival (OS) and progression-free survival (PFS) were analyzed. Kaplan-Meier survival analysis was performed and log rank test was used to analyze the difference between groups. P<0.2 or clinically significant indicators in univariate analysis were included in Cox regression model for multivariate survival analysis. Results: Among these 94 patients, there were 65 males and 29 females with an average age of (58.2±12.1) years; 33 patients with hypertension, diabetes mellitus, or cardiovascular and cerebrovascular diseases, 11 patients with family history of gastrointestinal tumors; 59 patients with tumors locating in the antrum or pylorus, 16 patients in the gastric body, 19 patients in the gastric fundus or cardia; 29 patients underwent total gastrectomy, 5 patients underwent proximal subtotal gastrectomy, and 60 patients underwent distal subtotal gastrectomy. In this study, 73 patients (77.7%) completed at least 5 cycles of adjuvant SOX regimen chemotherapy. Grade 3-4 adverse reactions included thrombocytopenia (23.4%, 22/94), nausea and vomiting (18.1%, 17/94) and peripheral neurotoxicity (6.4%, 6/94). Eighty-nine patients (94.7%) completed follow-up with a median follow-up time of 32 months. The 3-year and 5-year OS rates were 89.8% and 83.7%, respectively, and the 3-year and 5-year PFS rates were 81.4% and 78.1%, respectively. Taking 5 chemotherapy cycles as the cut-off point, the 3-year OS rate and 3-year PFS rate were 72.2% and 53.9% in the adjuvant chemotherapy < 5 cycles group, and 93.7% and 87.1% in the adjuvant chemotherapy ≥5 cycles group, respectively; the differences were statistically significant (P=0.029, P=0.006). Univariate analysis showed that the adjuvant chemotherapy < 5 cycles group was associated with worse 3-year OS (P=0.029). Multivariate analysis showed that insufficient chemotherapy cycle (HR=9.419, 95% CI: 2.330-38.007, P=0.002) was an independent risk factor for 3-year OS. Meanwhile, univariate analysis showed that the adjuvant chemotherapy <5 cycles (P=0.006), preoperative CEA > 4.70 μg/L (P=0.035) and adjacent organ resection (P=0.024) were associated with worse 3-year PFS. Multivariate analysis showed that adjuvant chemotherapy <5 cycles (HR=10.493, 95% CI: 2.466-44.655, P=0.001) and adjacent organ resection (HR=127.518, 95% CI: 8.885-1 830.136, P<0.001) were independent risk factors for 3-year PFS. Conclusions: Oxaliplatin combined with S-1 as an adjuvant chemotherapy regimen for locally advanced gastric cancer has high efficacy and low incidence of adverse reactions. At least 5 cycles of SOX regimen adjuvant chemotherapy can significantly improve prognosis of patients with stage II-III gastric cancer.

Effect of combination of acupuncture and psychological intervention on attention, response inhibition and cerebral blood flow in children with attention deficit hyperactivity disorder / 中国针灸

OBJECTIVE@#To observe the clinical curative effect on attention deficit hyperactivity disorder (ADHD) and explore the relevant mechanism of acupuncture in treatment.@*METHODS@#A total of 100 ADHD children were randomized into an observation group (50 cases, 2 cases dropped off) and a control group (50 cases, 1 case dropped off). In the control group, the routine psychological intervention was used. In the observation group, on the base of the treatment as the control group, acupuncture was applied to Taichong (LR 3), Neiguan (PC 6), Shenmen (HT 7), Sanyinjiao (SP 6), Baihui (GV 20), Sishencong (EX-HN 1), etc., once daily, for 3 months. The Cambridge neuropsychological tests automated battery (CANTAB) was adopted to evaluate attention and response inhibition in two groups before and after treatment. Digi-Lite color transcranial Doppler was used to measure cerebral arterial blood velocity. The therapeutic effect was compared between the two groups.@*RESULTS@#Regarding evaluation of attention, the mean delay time in the observation group after treatment was shorter than that before treatment and that in the control group separately (@*CONCLUSION@#Acupuncture combined with psychological intervention may improve attention and response inhibition in ADHD children, which is possibly related to the regulation of cerebral blood flow.

Pharmacoeconomic Evaluation of Peramivir versus Oseltamivir in the Treatment of Influenza Complicated with Febrile Seizures for Children / 中国药房

ABSTRACT OBJECTIVE：To compare the effectiveness and economics of peramivir and oseltamivir in the treatment of influenza complicated with febrile seizures in children. METHODS：In retrospective study，152 children with influenza complicated with febrile seizures were collected from our hospital during Dec. 2018 to Mar. 2019.They were divided into peramivir group（81 cases） and oseltamivir group （71 cases）. Fever remission time， medication duration， hospital duration， clinical efficacy （determined by convulsion，cough，nasal obstruction，runny nose，sore throat，etc.），the incidence of rash，the number of children with combined antibiotic and TCM were compared between 2 groups. Cost-effectiveness analysis was used to evaluate cost-effectiveness ratio（CER）and incremental cost-effectiveness ratio（ICER）of medication regimen in 2 groups. The sensitivity analysis of the effect and total cost were carried out with Logistic regression and multiple linear regression respectively through CER and ICER calculated by reducing 15％ drug price. RESULTS：There was no statistical significance in fever remission time， medication duration，hospitalization duration，the incidence of rash and proportion of children with combined antibiotics between 2 groups（P＞0.05）. There was statistical significance in proportion of children with combined TCM and clinical effect，and the proportion of children with combined TCM in peramivir group was significantly lower than oseltamivir group（P＜0.001）. Clinical effect of peramivir group was significantly better than that of oseltamivir group（P＝0.021）. Total cost of peramivir group and oseltamivir group were 5 442.84 yuan/person and 5 571.71 yuan/person（P＝0.795）；CER of them were 54.47 and 56.51；ICER of peramivir group was － 89.38. The results of sensitivity analysis were consistent with those of basic analysis.CONCLUSIONS： Compared with oseltamivir，peramivir is more effective and less costly for children with influenza and febrile seizures.

Effect of maternal immune level at different pregnancy stages on cow's milk protein allergy in infants / 中国当代儿科杂志

OBJECTIVE@#To study the association between maternal Th1/Th2 immune level at different pregnancy stages and cow's milk protein allergy (CMPA) in infants.@*METHODS@#The healthy women with a singleton pregnancy, as well as their offspring, who attended Yidu Central Hospital of Weifang and Qingzhou Traditional Chinese Medicine Hospital from July 2016 to December 2018 were enrolled. The maternal levels of interleukin-2 (IL-2), interferon gamma (IFN-γ), interleukin-4 (IL-4), and interleukin-10 (IL-10) at the second and third trimesters of pregnancy were measured. A CMPA questionnaire survey was conducted within one year after birth. Food avoidance and cow's milk oral challenge tests were performed in infants suspected of CMPA. The 48 infants who met the diagnostic criteria for CMPA were included in the observation group, and the remaining 977 normal infants were included in the control group. A univariate analysis was performed on the infants with CMPA. A Poisson regression analysis was used to determine the association between maternal Th1/Th2 immune factors at different pregnancy stages and CMPA.@*RESULTS@#The detection rate of CMPA was 4.68%. The clinical manifestations included the symptoms of the digestive system, skin, and respiratory system and other symptoms. The univariate analysis showed that compared with the control group, the observation group had significantly higher incidence rates of maternal food allergy and maternal history of allergic diseases (P<0.05) and a significantly lower breastfeeding rate (P<0.05). The observation group had significantly lower maternal levels of IL-2 (second and third trimesters) and IFN-γ (third trimester) than the control group (P<0.05). Maternal low IFN-γ at the third trimester and maternal low IL-2 at the second and third trimesters were significantly associated with CMPA in infants (P<0.05). After correction of the factors of breastfeeding, maternal food allergy, and maternal history of allergic diseases, it was found that maternal low IL-2 and IFN-γ at the third trimester were still significantly associated with CMPA in infants (P<0.05).@*CONCLUSIONS@#The maternal decrease in Th1 level at the third trimester of pregnancy may lead to the change in fetal immunity and thus increase the risk of CMPA in offspring.

High-resolution Anorectal Manometry in the Diagnosis of Functional Defecation Disorder in Patients With Functional Constipation: A Retrospective Cohort Study

BACKGROUND/AIMS: High-resolution anorectal manometry (HRAM) has been considered a first-line diagnostic tool for functional defecation disorder. However, clinical studies on HRAM used in constipation patients are very limited and few studies have reported the characteristics of anorectal pressure in Chinese patients. The aim of this study is to investigate the characteristics of motility data in a cohort of Chinese patients with functional constipation. METHODS: A total of 82 consecutive patients with functional constipation who underwent a standardized HRAM were retrospectively enrolled in this study. The functional defecation disorder was classified into Rao's types. RESULTS: The mean age of 82 patients was 51 years (range, 16–83 years). Indications for anorectal manometry were functional constipation for all patients. The mean resting pressure was 69.2 ± 21.2 mmHg (range, 24.5–126.9 mmHg). The mean maximum squeezing pressure was 198.4 ± 75.6 mmHg (range, 54.2–476.9 mmHg). The mean length of the anal high pressure zone was 3.4 ± 1.0 cm (range, 0.6–4.9 cm). Sixty (73.2%) patients were diagnosed as functional defecation disorder. In attempted defecation, type I was most common (n = 24), followed by type II (n = 12), type III (n = 11), and type IV (n = 13) that were present on HRAM according to Rao's classification. In all 60 patients with functional defecation disorder, 37 were women and 23 were men. Men were significantly more likely than women to have functional defecation disorder (92.0% vs 64.9%, P = 0.014). CONCLUSION: HRAM could be used as a test for the diagnosis of functional defecation disorder and functional defecation disorder is common in Chinese patients with functional constipation.

Clinical therapeutic effects of endoscopic drug therapy for treatment of patients with acute esophageal and gastric variceal bleeding / 中国中西医结合急救杂志

Objective To observe the effects of endoscopic drug therap on hemostasis, re-bleeding and the risk of occurrence of complication in patients with acute esophageal and gastric variceal bleeding (EGVB). Methods A retrospective method was conducted, and 100 patients with EGVB who were admitted to the Affiliated Hospital of Yan'an University from June 2015 to June 2017 were enrolled. According to the difference in treatment methods, they were divided into an endoscopy Sclerotherapy and Ligation group and transjugular intrahepatic portosystemic shunt (TIPS) group, 50 cases in each group. The TIPS group was treated with TIPS; the endoscopy Sclerotherapy and Ligation group underwent endoscopic variceal sclerotherapy, endoscopic esophageal variceal ligation and postoperative non-selective β blockers oral administration. After 2 years of follow-up, the patients' hemostasis, re-bleeding at acute stage, survival situation and the incidences of complications were recorded. Before treatment and 2 weeks after treatment, the levels of serum albumin (Alb), total bilirubin (TBil) and platelet count (PLT) were measured by Hitachi automatic biochemical analyzer in the two groups. Results The success rate of hemostasis in the endoscopy Sclerotherapy and Ligation group was significantly higher than that in the TIPS group [98.0% (49/50) vs. 82.0% (41/50) ], and the recurrence rate of varices, during 1- and 2-year follow-up, the recurrence rate of bleeding and the incidences of complications were significantly lower than those in TIPS group [the recurrence rate of varicose veins: 6.0% (3/50) vs. 24.0 (12/50), 1-year re-bleeding rate: 12.0% (6/50) vs. 30.0% (15/50), 2-year re-bleeding rate: 42.0% (21/50) vs. 66.0% (33/50), esophageal ulcer: 2.0% (1/50) vs. 14.0% (7/50), upper abdominal discomfort: 2.0% (1/50) vs. 14.0% (7/50), hepatic encephalopathy:4.0% (2/50) vs. 16.0% (8/50), chest pain: 6.0% (3/50) vs. 20.0% (10/50), all P < 0.05]. After treatment, the levels of Alb and PLT in the endoscopy Sclerotherapy and Ligation group were higher than those in the TIPS group [Alb (g/L):43.84±4.34 vs. 40.83±3.21, PLT (×109/L): 26.33±3.37 vs. 21.12±3.89, both P < 0.05], and the TBil was lower than that in the TIPS group (μmol/L: 13.82±4.32 vs. 19.33±4.59). Conclusion Endoscopic Sclerotherapy and Ligation can significantly improve the effect of hemostasis of patients with acute EGVB, the rate of re-bleeding does not increase compared with that of western medicine group using TIPS, and the incidences of complications are significantly lower than those of applying TIPS.

Acupuncture combined with medication improves endocrine hormone levels and ovarian reserve function in poor ovarian response patients undergoing in vitro fertilization-embryo transplantation / 针刺研究

OBJECTIVE: To observe the clinical effect of acupuncture plus medication in the treatment of poor ovarian response (POR) patients and to explore its mechanisms in assisting pregnancy. METHODS: A total of 100 volunteer POR women undergoing in vitro fertilization-embryo transplantation (IVF-ET) were recruited in the present study. On the 1st cycle of IVF-ET, these POR women received microstimulation of ovulation program (oral administration of Clomiphene, muscular injection of Menotrophin, Chorionic Gonadotrophin triggering, etc.). Before receiving the 2nd period of IVF-ET, these patients were equally and randomly divided into control, medication (Climen, composed of estradiol valerate and cyproterone acetate), acupuncture and acupuncture+medication (combined treatment) groups according to the random number table. Patients of the medication group were asked to orally take Climen (1 tablet/d for 21 days) beginning from the 3rd day of the menstruation, which was repeated for 3 menstrual cycles. Patients of the acupuncture group received manual acupuncture stimulation of Guanyuan (CV4), and bilateral Taixi (KI3), Sanyinjiao (SP6) of and Tai-chong (LR3) from day 8 to 15 of menstruation (follicular phase), once daily for 3 menstrual cycles. On the 2nd day of menstruation of the 1st and 2nd IVF-ET cycle, the ovarian reserve function was detected, including measurement of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) contents by using radioimmunoassay, and serum anti-mullerian hormone (AMH) level by using ELISA, and the antral follicles count (AFC) of the ovaries by using a color Doppler ultrasonic diagnosis apparatus. At the end of ovulation induction, the assisted pregnancy indexes and outcomes were detected, including administration of dosage and days of gonadotropin (Gn), the diameter of dominant oocyte, level of E2 on the trigger day, the numbers of ultrasound-guided-retrieved oocyte and the cultivated high-quality embryo (grade 1 and 2). RESULTS: After the treatment, the contents of serum FSH, LH and E2 in the medication, acupuncture and combined treatment groups were significantly reduced (P0.05). CONCLUSION: Acupuncture combined with medication improves the level of endocrinal hormones and ovarian reservation function in POR women undergoing IVF-ET, benefiting the ovary environment of pregnancy.

Relationships between the enrichment of ETBF, Fn, Hp in intestinal and colorectal cancer / 中华肿瘤杂志

Objective@#To explore relationships between the enrichment of ETBF, Fn, Hp in feces, tissues and colorectal cancer.@*Methods@#Feces, lesion tissue and adjacent tissue from 24 patients with colorectal cancer and 31 patients with adenomas were collected, and we collected Feces and tissue of 20 healthy control persons. Then the copy numbers of enterotoxigenic B. fragilis (ETBF), Fusobacterium nucleatum (Fn) and Helicobacter pylori (Hp) were determined by quantitative real-time PCR. Immunohistochemical method was used to examine the expression intensity of EGFR and p53, and the relationships between different expression intensity of EGFR, p53 and the numbers of three bacterias.@*Results@#In the feces, copy numbers of ETBF and Fn were as follous: colorectal cancer group>adenomas group>healthy control group (P<0.05). Copy numbers of Hp were as follous: colorectal cancer group>healthy control group (P<0.01); adenomas group>healthy control group (P<0.01). In the tissue, copy numbers of ETBF, Fn were as follows: colorectal cancer group>adenomas group>healthy control group (P<0.05). Copy numbers of Hp were as follows: colorectal cancer group>healthy control group (P<0.01); adenomas group>healthy control group (P<0.01). Copy numbers of those three bacteria in the lesion tissue and the adjacent tissue had no significant difference. This happened both in colorectal cancer group and adenomas group. The different expression intensity of EGFR, p53 and the number of three bacteria showed no obviously statistical correlation(P>0.05).@*Conclusion@#Adenomatous polyp and colorectal cancer patients show high enrichment of ETBF, Fn and Hp in both feces and tissues. ETBF, Fn and Hp probably contribute to the development of adenomatous polyp and colorectal cancer. Trial registration Chinese Clinical Trial Registry, ChiCTR-BOC-17012509.

Simultaneous determination of flavonol glycoside and its major metabolites by LC-MS/MS in rat plasma / 药学学报

Flavonol glycoside is in clinical trials for treatment of hyperlipidemia. An accurate and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of flavonol glycoside (M0), aglycone (M1) and glucuronide conjugate (M2) in rat plasma. d6-Flavonol glycoside was used as internal standard (IS). After extraction from the plasma by protein precipitation, the analytes and internal standard were separated on a XDB C18 column (50 mm×4.6 mm, 1.8 μm) using a gradient elution procedure. The mobile phase consisted of methanol and water (0.2% formic acid) at a flow rate of 0.6 mL·min−1. The total run time was 4.5 min. Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 461.3 → m/z 299.1 for M0, m/z 299.1 → m/z 283.1 for M1, m/z 475.0 → m/z 299.1 for M2, and m/z 467.3 → m/z 305.1 for d6-flavonol glycoside. The method was validated and successfully applied to the pharmacokinetics study of flavonol glycoside in SD rats which were given flavonol glycoside (30 mg·kg−1) by gavage. The Cmaxof M0 is (341 ±106) ng·mL−1 and AUC0−t is (1 960 ±725) h·ng·mL−1, while the Cmaxof M2 is (1 720 ±843) ng·mL−1and AUC0−t is (8 510 ±2 920) h·ng·mL−1. The results suggest that flavonol glycoside existed mainly in the form of M0 and M2 in rats. After flavonol glycoside being hydrolyzed by the intestinal flora, it was absorbed in the form of aglycone and further metabo­lized to M2 after the first-pass effect. In this paper, the main metabolites of flavonol glycoside in rat plasma were determined for the first time, which provided a basis for the design of clinical pharmacokinetic experiment.