Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P＜0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P＜0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Objectives:To investigate the mutation of PIK3CA in colorectal cancer and to analyze their clinicopathological features, and evaluate their role in clinical treatment and prognostication.Methods:A total of 128 paraffin-embbeded tissue samples of colorectal cancer from Shanxi Cancer Hospital from 2018 to 2021 were collected. DNA was extracted from the samples, and next-generation sequencing (NGS) was used to detect PIK3CA mutation. The relationship between PIK3CA mutation, their clinicopathological features, and prognosis were analyzed.Results:Among the 128 colorectal cancer samples, there were 75 males and 53 females; with aged range 32-86 years, median 61.5 years, 27 (21.09%) had PIK3CA mutations. Colorectal cancer with PIK3CA mutation was more likely to occur in male patients ( P=0.007), which was related to tumor site ( P=0.032), tumor size ( P=0.029) and TP53 wild-type ( P=0.001). The common site mutations of PIK3CA mostly occurred in tumors with tumor mutation burden≥10 Muts/Mb ( P=0.031).PIK3CA mutation had no significant effect on the survival prognosis of patients, but the efficacy of anti-angiogenic therapy was poor in these patients. Conclusions:PIK3CA mutation is a common mutation in colorectal cancer and plays an important role in the occurrence and development of colorectal cancer. PIK3CA mutation may lead to resistance to anti-angiogenic drugs in colorectal cancer, but its impact on survival and prognosis to patients needs further study.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective:To explore the value of tumor stroma ratio (TSR) in non-small lung cancer (NSCLC) tissue in predicting the efficacy of tumor immunotherapy.Methods:The clinical and histopathological data of patients with stage ⅢB-Ⅳ NSCLC treated with immune checkpoint inhibitors in the Renmin Hospital of Wuhan University from January 2017 to December 2020 were collected. Taking 50% as the TSR boundary value, the patients were divided into low TSR group (≤50%) and high TSR group (>50%) . The histopathological features, 4-cycle objective response rate (ORR) and disease control rate (DCR) , 6-cycle ORR and DCR, and progression-free survival (PFS) were compared between the two groups. Univariate and multivariate Cox regression models were used to analyze the prognostic factors related to PFS.Results:A total of 50 patients were included, including 27 with low TSR and 23 with high TSR. There were no significant differences between the two groups in age ( χ2=0.59, P=0.441) , gender ( P=0.578) , smoking history ( χ2=0.12, P=0.730) , histopathological type ( χ2=2.33, P=0.313) , TNM stage ( χ2=0.22, P=0.636) , 4-cycle ORR ( χ2=0.48, P=0.487) and DCR ( P=0.593) , 6-cycle ORR ( χ2=0.05, P=0.818) and DCR ( P=0.641) . The incidence of brain metastasis was higher in the high TSR group than that in the low TSR group [34.8% (8/23) vs. 7.4% (2/27) , χ2=4.23, P=0.040]. Kaplan-Meier survival analysis showed that the PFS in the low TSR group was significantly longer than that in the high TSR group (15.6 months vs. 10.2 months, χ2=13.84, P<0.001) . Univariate analysis showed that TSR value ( HR=0.29, 95% CI: 0.14-0.58, P<0.001) and brain metastasis ( HR=2.38, 95% CI: 1.12-5.05, P=0.024) were correlated with the worse prognosis of NSCLC patients. Multivariate Cox regression analysis showed that TSR value was an independent prognostic factor for NSCLC immunotherapy ( HR=0.32, 95% CI: 0.14-0.70, P=0.004) . Conclusion:TSR is an independent predictor of immunotherapy for NSCLC, but whether it can predict the short-term efficacy of immunotherapy for advanced NSCLC still needs further research.

Objective:To investigate the incidence of social isolationin community elderly patients with knee osteoarthritis and analyze its influencing factors.Methods:From January to April 2021, 240 community elderly with knee osteoarthritis in three community health service centers in Taiyuan (Yingbin community, Dawang community and Pingyang second community) were selected as research objects by convenient sampling method. They were investigated by general data questionnaire, Lubben Social Network Scale-6(Lubben-6), Geriatric Depression Scale-15, Perceived Social Support Scale, Numerical Rating Scale. Single factor analysis and binary Logistic regression analysis were used to explore the influencing factors of social isolation in elderly patients with knee osteoarthritis.Results:The prevalence of social isolation among community elderly patients with knee osteoarthritis was 43.33% (104/240) . The results of binary logistic regression analysis showed that age ( OR = 2.228, 95% CI 1.436-3.457), complicated diseases ( OR = 1.733, 95% CI 1.028-2.919), exercise ( OR = 0.560, 95% CI 0.360-0.869), depression ( OR = 3.603, 95% CI 1.768-7.339), comprehension of social support ( OR = 0.424, 95% CI 0.253-0.710) and pain ( OR = 1.792, 95% CI 1.147-2.799) were the influencing factors of social isolation in elderly patients with knee osteoarthritis ( P<0.05). Conclusions:The degree of social isolation in community elderly patients with knee osteoarthritis is relatively high, and is affected by many factors. Community medical staff should formulate targeted nursing intervention plans based on their influencing factors to reduce the occurrence of social isolation.

Objective: To describe the epidemiological characteristics of a cluster of COVID-19 cases reported in Baodi district of Tianjin as of 18 February, 2020, which might be associated with the exposure in a local department store, and provide suggestions for prevention and control strategy development. Methods: The basic characteristics, time and area distributions, clinical manifestations, epidemiological history and transmission mode of the COVID-19 cases associated with the department store exposure were analyzed. Results: A total of 40 COVID-19 cases were associated with the department store exposure, accounting for 75.47% of the total confirmed cases (53 cases) reported in Baodi district. The cases were mainly at the age of 60 years or older (35.00%) and farmers (40.00%). The main clinical manifestations included fever (95.00%), cough (35.00%), and diarrhea (15.00%). The proportion of confirmed severe cases was 32.50%. The incidence curve showed that the incidence peak occurred on 31 January, 2020. Among the 40 cases, 6(15.00%) were department store employees, 19(47.50%) were customers and 15(37.50%) were close contacts (secondary cases). The first case occurred on 21 January, 2020, this case was a department store employee who had a purchasing history at whole sale markets in other provinces and cities before the onset, and 3 employees were still on duty after symptom onsets. The median of the incubation period of customer cases was 6 days, and the median of the interval between onset and medical treatment of customer cases was 7 days. Conclusion This was a cluster epidemic of COVID-19, which might be associated with the exposure in the department store. By now, the current prevention and control measures have achieved satisfied effects.

Objective:To study the characteristics and influence factors of laboratory test results of confirmed COVID-19 cases in Tianjin.Methods:Sample collection was conducted based on the standard operating procedure. Tianlong automatic magnetic bead nucleic acid extraction reagent was used for RNA extraction. Real-time RT-PCR was performed using four approved COVID-19 nucleic acid detection kits. Related epidemiological data of the cases were collected. One-way analysis of variance and non-parametric test for inter-group differences analysis were conducted using SPSS25.0 software.Results:A total of 162 PCR tests were completed for novel coronavirus nucleic acid detection in 123 confirmed COVID-19 cases. Eleven PCR results were positive for a single target gene and 10 of which were positive for nucleocapsid protein (N) gene. Nineteen cases were tested with two kinds of nucleic acid detection kits and the results of different detection kits were different. Different types of samples were collected form 13 cases for nucleic acid detection and the results showed that the Ct value of sputum sample was lower than that of throat swab sample. No significant difference in Ct values of throat swab samples was observed among patients with different clinical symptoms ( PCt-N=0.797, PCt-ORF1a/b=0.551). The 123 cases were divided into different groups according to the time interval between the onset date and the date of the first positive detection of viral nucleic acid. No significant difference in Ct values of throat swab samples was observed among different time interval groups ( PCt-N=0.373, PCt-ORF1a/b=0.058). Conclusions:Sputum samples were better than upper respiratory tract samples for viral nucleic acid detection. The sensitivity of N gene detection was higher, but re-sampling was needed when the result was positive for the single target N gene. Appropriate detection kits should be selected according to the actual needs, and samples should be collected at multiple time points, in multiple types and form multiple sites for detection.

Objective: To compare droplet digital PCR (ddPCR) and Super-amplification refractory mutation system (ARMS) in the detection of T790M mutation of epidermal growth factor receptor (EGFR) in the plasma of non-small cell lung cancer patients who had developed resistance to EGFR tyrosine kinase inhibitor (TKI) , and to investigate the clinical application of ddPCR. Methods: Plasma samples were collected from non-small cell lung cancer patients who had acquired EGFR-TKI resistance at Shanghai Pulmonary Hospital, Tongji University, from May 2017 to November 2017. Extracted ctDNA was analyzed by ddPCR and Super-ARMS to evaluate the T790M mutation status of EGFR gene. Results: A total of 37 patients with activating EGFR mutation that acquired resistance to EGFR-TKI were selected in the study, including 17 male and 20 female with a median age of 64 years (range 40-83 years). Before TKI treatment, all the patients harbored EGFR inhibitor sensitive mutations but without T790M mutation. After acquiring resistance to EGFR-TKI treatment, the T790M mutation rate detectable by ddPCR was 45.9% (17/37). In contrast, the mutation rate of T790M detectable by Super-ARMS was 35.1% (13/37, P<0.05). For the 13 positive cases detected by Super-ARMS (ΔCt<8), they were all positive by ddPCR assay; Among the 10 negative cases detected by Super-ARMS (ΔCt≥8), there were 3 cases positive by ddPCR assay. For patients without ΔCt by Super-ARMS assay, there was one weak positive case detectable by ddPCR assay. Among 17 EGFR T790M positive patients, 9 received EGFR inhibitor Osimertinib treatment, and 7 of them had good therapeutic response after the treatment. Conclusions While a significant correlation between the two methods is shown. ddPCR is more sensitive than Super-ARMS in the detection of EGFR T790M mutation, indicating that it is a better method in guiding target drug therapy of non-small cell lung cancer patients after acquiring the resistance to EGFR-TKI.

Purpose To explore the clinicopathological features,immunophenotype,differential diagnosis and prognosis of the composite pheochromocytoma (CP)-ganglioneuroma.Methods 3 cases of CP-ganglioneuroma were stained by immunohistochemical SP method,and the related literatures were reviewed.Results 3 cases of CP-ganglioneuroma were one male and 2 females,the age were 37-64.Case 3 were of primary mediastinal.Microscopically,the tumor tissues were composed of two components:one type of tumor cells were arranged in nests with a predominant Zellballen pattern,round or oval nuclei,fine granular cytoplasm and rare mitotic,another part of the neoplasm showed scattered and aggregated distributed ganglion cells in the background of neurofibromatosis which aligned bundles and interwoven,the edge of the tumor was still residual adrenal tissue.Immunohistochemically,components of pheochromocytoma were positive for CD56,CgA,Syn,vimentin and negative for SMA,Melan-A,α-inhibin NF with low Ki-67 proliferation index.S-100 was positive in supporting cells,ganglioneuroma components were positive for NF,S-100 with low Ki-67 proliferation index.CgA and Syn were weakly positive or negative in the ganglion cells.Conclusion CP is a relatively rare tumor,which can not be distinguished from pheochromocytoma in clinical and radiological diagnosis.The corresponding clinical treatment and follow-up management should be taken according to the different ingredients (benign or malignant).