Objective:To investigate the expression of programmed cell death ligand 1 (PD-L1), clinicopathologic features, immunohistochemical expression and molecular characteristics in fumarate hydratase (FH)-deficient renal cell carcinoma and to explore the potential application of immunotherapy in the patients.Methods:There were six patients with FH-deficient renal cell carcinoma treated at the First Affiliated Hospital of Fujian Medical University between January 2020 and October 2022. The clinical data, histological morphology, immunophenotype, PD-L1 expression and next-generation sequencing results were tabulated and analyzed.Results:There were 6 patients, all male, age ranged from 37 to 72 years (mean 45.7 years). Four cases were high-grade (WHO/ISUP grade3-4) with 2 or more histologic patterns, including papillary (most common), glandular, tubular, vesicular, ethmoid, nest-like, cystic and solid structures. Two cases were low-grade which showed nest-like, glandular, or tubular arrangement with eosinophilic flocculent cytoplasm and small intracellular vacuoles. Immunohistochemical analysis revealed strong expression of 2SC in all 6 cases, negative expression of FH in 5 cases, and positive expression of GATA3 in 5 cases. In high-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes in advanced tumor invasion were 180.3/mm 2 and 130.5/mm 2, respectively. PD-L1 combined positive scores (CPS) were 20, 50, 5 and 30, respectively. The Ki-67 proliferative index were 20%, 20%, 10% and 30%, respectively. In low-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes were 123.0/mm 2 and 100.5/mm 2, respectively. The PD-L1 CPS score was 1, and the Ki-67 proliferation index was 3%. High-throughput sequencing showed FH gene somatic mutation in 3 cases, FH gene germline mutation in 2 cases, and FH gene mutation was not detected in one case. Conclusion:FH-deficient renal cell carcinoma is more commonly high-grade than low grade. FH and 2SC are immunohistochemical markers used in the diagnosis of FH-deficient renal cell carcinoma, and GATA3 positivity is supportive of the diagnosis. The tumor infiltration of high-grade FH-deficient renal cell carcinoma shows an increase in CD4 and CD8 positive T-lymphocytes, and high expression of PD-L1; thus, anti-PD-L1 immunotherapy can be used as a treatment option.

OBJECTIVE: To investigate the effect of hyperbaric oxygen (HBO) on paroxysmal sympathetic hyperexcitation (PSH) after brain injury. METHODS: A multicenter retrospective study was conducted. Fifty-six patients with PSH who received HBO treatment from four hospitals in Henan Province from January 2021 to September 2023 were selected as the HBO group, and 36 patients with PSH who did not receive HBO treatment from Zhengzhou People's Hospital from May 2018 to December 2020 were selected as the control group. PSH assessment measure (PSH-AM) score [clinical feature scale (CFS) score+diagnostic likelihood tool (DLT) score] and Glasgow coma scale (GCS) were compared before and after HBO treatment, and between HBO group and control group to evaluate the effect of HBO treatment on prognosis of PSH patients. RESULTS: There were no statistically significant differences in age, gender, PSH etiology, GCS score, time from onset to occurrence of PSH, CFS score, CFS+DLT score and frequency of PSH episodes between the two groups, indicating comparability. The duration of HBO treatment ranged from 3 to 11 days for 56 patients receiving HBO treatment, and the duration of HBO treatment ranged from 3 to 5 courses. Compared with before treatment, after HBO treatment, PSH symptoms in HBO patients were significantly relieved (body temperature increase: 14.29% vs. 64.29%, heart rate increase: 25.00% vs. 98.21%, shortness of breath: 14.29% vs. 76.79%, blood pressure increase: 8.93% vs. 85.71%, sweating: 10.71% vs. 85.71%, muscle tone increased: 19.64% vs. 75.00%, all P < 0.05), CFS+DLT score decreased significantly (16.90±4.81 vs. 22.12±3.12, P < 0.01), GCS score improved (12.31±5.34 vs. 5.95±2.18, P < 0.01). After 30 days of hospitalization, compared with the control group, PSH symptoms in the HBO group were improved (body temperature increase: 14.29% vs. 19.44%, heart rate increase: 19.64% vs. 25.00%, shortness of breath: 10.71% vs. 27.78%, blood pressure increase: 7.14% vs. 22.22%, sweating: 8.93% vs. 25.00%, muscle tone increased: 19.64% vs. 38.89%, all P < 0.05 except body temperature increase), CFS+DLT score decreased (16.90±3.81 vs. 19.98±4.89, P < 0.05), GCS score increased (14.12±4.12 vs. 12.31±4.14, P < 0.01), the length of intensive care unit (ICU) stay was shortened (days: 18.01±5.67 vs. 24.93±8.33, P < 0.01). CONCLUSIONS HBO treatment can significantly relieve the symptoms of patients with PSH after brain injury and provide a new idea for the treatment of PSH patients.
Humans ; Hyperbaric Oxygenation/methods* ; Retrospective Studies ; Brain Injuries/therapy* ; Female ; Male ; Prognosis ; Glasgow Coma Scale ; Autonomic Nervous System Diseases/etiology*

Objective:To investigate the correlation between lung ultrasound score at the end of spontaneous breathing trial (SBT) and cumulative fluid balance at 48 h and their predictive value of extubation outcome in patients with intro-abdominal infection (IAI) under mechanical ventilation.Methods:A retrospective study was conducted. Patients with IAI under mechanical ventilation for more than 48 h were collected from three hospitals from October 1, 2017 to September 30, 2018. Routine demographic variables and clinical characteristics were recorded. The patients were divided into the successful extubation group and failed extubation group according to whether they could maintain spontaneous breathing for 48 h after extubation. LUS at the end of SBT (before extubation) and cumulative fluid balance at 48 h were compared between the two groups. LUS and cumulative fluid balance at 48 h were analyzed by bivariate correlation analysis, and their correlations with shallow fast breathing index (RSBI) and precursor protein of BNP (Pro-BNP) were analyzed. The predictive value of LUS at the end of SBT (before extubation) and cumulative fluid balance for extubation failure were analyzed by receiver operating characteristic curve (ROC).Results:Totally 207 patients were enrolled. There were significant differences in LUS before extubation [12 (10, 14) vs. 16 (14, 17) points], cumulative fluid balance [-318 (-1 116, 200) mL vs. 1 140 (685, 1 614) mL], RSBI [60 (55, 66) (times/min)/L vs. 70 (65, 78) (times/min)/L], pro-BNP [250 (122, 1 292) pg/mL vs. 1156 (285, 4 346) pg/mL], IAP >15 mmHg [32.8% vs. 46.6%], and ICU stay [8 (6, 12) days vs. 11 (8, 14) days] ( P<0.05). Logistic regression analysis showed that the COPD history, RSBI, LUS at the end of SBT, and cumulative fluid balance at 48 h before extubation were independent risk factors for extubation failure. Correlation analysis showed that LUS was moderately correlated with cumulative fluid balance at 48 h ( r=0.41, P<0.001), weakly correlated with RSBI ( r=0.381, P<0.001), and weakly correlated with pro-BNP ( r=0.220, P<0.001). Cumulative fluid balance at 48 h was weakly correlated with RSBI ( r=0.31, P<0.001), but not with pro-BNP. LUS at the end of SBT and cumulative liquid balance at 48 h had predictive value for extubation failure [AUC=0.87 (95% CI: 0.82-0.91), AUC=0.89 (95% CI: 0.85-0.94), P<0.001]. Conclusions:There is a moderate correlation between LUS at the end of SBT (before extubation) and 48 h cumulative fluid balance in patients with IAI and mechanical ventilation. LUS at the end of SBT (before extubation) and cumulative fluid balance at 48 h have some predictive value for extubation failure.

Objective:To evaluate the value of lung ultrasound score (LUS) on predicting weaning outcome in patients with intro-abdominal infection (IAI) undergoing mechanical ventilation.Methods:Patients with IAI undergoing mechanical ventilation admitted to Research Institute of General Surgery of East War Zone Hospital and intensive care unit (ICU) of the First People's Hospital of Lianyungang from January to December in 2018 were included. The patients who satisfied weaning criteria were enrolled in the weaning process, which included spontaneous breathing trial (SBT) and extubation. They were divided into SBT success group and SBT failure group according to whether passed 120-minute SBT or not. LUS scores before and after SBT were compared between the two groups. The patients in the SBT success group were extubated, and they were divided into successful extubation group and failed extubation group for sub-group analysis according to whether re-intubation was needed in 48 hours after extubation. LUS score before extubation (at the end of SBT) and 48 hours after extubation (48 hours after extubation in the successful extubation group or before re-intubation in the failed extubation group) were compared. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of LUS score before SBT for SBT failure and LUS score before extubation for the failure.Results:A total of 76 patients with IAI undergoing mechanical ventilation were included. Twenty-three patients had duration of mechanical ventilation less than 48 hours, severe chronic obstructive pulmonary disease (COPD), tracheotomy or automatic discharge were excluded, and 53 patients were enrolled. SBT was failed in 9 patients, and successfully performed in 44 patients, of whom 23 patients with successful extubation, and 21 with failed extubation. The LUS scores before and after SBT in the SBT failure group were significantly higher than those in the SBT success group (before SBT: 13.22±1.99 vs. 10.79±1.64, t = -3.911, P = 0.000; after SBT: 19.00±1.12 vs. 13.41±1.86, t = -8.665, P = 0.000). ROC curve analysis showed that the area under ROC curve (AUC) of LUS score before SBT for predicting SBT failure was 0.82 [95% confidence interval (95% CI) was 0.67-0.98, P = 0.002]. When the optimum cut-off value was 12.5, the sensitivity was 66.7%, and the specificity was 84.1%. Sub-group analysis showed that the LUS scores before and after extubation in the failed extubation group were significantly higher than those in the successful extubation group (before extubation: 14.19±1.60 vs. 12.69±1.81, t = -2.881, P = 0.006; after extubation: 16.42±1.59 vs. 12.78±1.54, t = -7.710, P = 0.000). ROC curve analysis showed that the AUC of LUS score before extubation for predicting the failure was 0.81 (95% CI was 0.69-0.92, P = 0.000). When the optimum cut-off value was 13.5, the sensitivity was 80.0%, and the specificity was 65.2%. Conclusion:LUS score can effectively predict SBT outcome, risk of re-intubation after extubation in patients with IAI undergoing mechanical ventilation.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics and differential diagnosis of primary skull base chondrosarcoma.Methods:Nine cases of primary skull base chondrosarcoma were collected at the First Affiliated Hospital of Fujian Medical University, from January 2006 to June 2019, reviewed for the clinical and radiologic data and morphologic features, immunophenotype and molecular characteristics.Results:Among all the 9 cases, six were male, three were frmale, with average age 47 years, and median age 47 years; five cases were WHO gradeⅠ, and four were WHO grade Ⅱ. Microscopically, the tumor showed lobulated growth pattern with low-medium cellularity within a chondroid or mucoid background. The tumor cells showed mild-moderate atypia, with binucleated forms, and mitosis was rare or occasional. Immunohistochemistry (IHC) showed tumor cells were positive for S-100 protein, vimentin, SOX-9 and D2-40, and negative for Brachyury, CK, EMA and CK8/18; the Ki-67 index was low (1% to 5%). Molecular analysis showed IDH1 R132C mutation in four cases.Conclusions:Skull base chondrosarcoma is a rare cartilaginous malignant tumor with a good prognosis. Its characteristic morphologies, combined with IHC and molecular detection are helpful for the differential diagnosis.

Objective: To learn the epidemiological characteristics of fall mortality among the elderly people in Taizhou，and to provide basis for intervention strategies of fall in the elderly. Methods: Data of fall mortality among residents aged 60 years or over in Taizhou from 2016 to 2018，collected from Zhejiang Chronic Disease Surveillance Information Management System，was used for analysis of time，population and geographical characteristics of fall deaths. The epidemic trend of fall mortality in the elderly was described by annual percentage change（APC）. Results: From 2016 to 2018，3 699 cases of fall death in Taizhou were reported，the crude and standardized mortality were 116.90/100 000 and 97.88/100 000. The standardized mortality of fall in women was 106.11/100 000，which was higher than 90.13/100 000 in men（P<0.05）. The standardized mortality of fall in rural residents was 131.20/100 000，which was higher than 28.15/100 000 in urban residents（P<0.05）. The mortality of fall in residents aged 65-69 years from 2016 to 2018 showed an upward trend（APC=4.20%，P<0.05），while the mortality trend of fall in other age groups was not statistically significant（P>0.05）. Conclusion Fall was the first cause of injury death in the elderly aged 60 years or over in Taizhou. Females and rural residents have relatively higher fall mortality.

Objective To observe the effect of hyperbaric oxygen (HBO) therapy combined with repeated transcranial magnetic stimulation (rTMS) on patients with cognitive dysfunction after cerebral infarction.Methods A total of 81 patients with cognitive dysfunction after cerebral infarction were randomly divided into a control group,an HBO group and a combined treatment group,each of 27.In addition to basic medication and traditional rehabilitation therapy,the HBO group was also treated with hyperbaric oxygen,while the combined treatment group received both HBO and rTMS.The mini-mental state examination (MMSE) and the Montreal cognitive assessment (MoCA) were administered before and after the four weeks of treatment.Results The average MMSE scores of the HBO and combined treatment groups were both significantly higher than that of the control group,with the former significantly higher than the latter.Moreover,the average MoCA score of the HBO group was also significantly higher than that of the combined treatment group,and both were significantly higher than that of the control group.Conclusion Hyperbaric oxygen therapy can more effectively improve the cognitive function of patients with cognitive dysfunction after the cerebral infarction when it is combined with repeated transcranial magnetic stimulation.

BACKGROUND: The clinical features of patients with common single-mutation of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) has been well characterized. There is a high adenocarcinoma incidence rate among female patients with none or shorter smoking history. Those patients have higher objective response rate (ORR) and progression free survival (PFS) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, it is still unclear that the clinical features of patients with EGFR double mutation and the sensitivity towards EGFR-TKIs treatment. METHODS: We performed a retrospective cohort study of 1,238 primary NSCLC patients who had EGFR gene testing in Affiliated Hospital of Qingdao University from January 1, 2015 to December 31, 2016 and identified 603 patients with single mutation and 59 patients with double mutation. All genes were uniformly detected by using ARMS-PCR technology. We analyze the gene of 32 double-mutant patients with specific genotyping, and randomly selected 60 patients with single mutation and compared the clinical features with 59 patients with double mutation. Furthermore, we examined the efficacy of EGFR-TKIs treatment in lung cancer patients with double mutation and single mutation in EGFR. RESULTS: The rare single mutation gene is the most common in patients with double mutation of EGFR. There is no significant statistical difference in gender, smoking history, age, pathological type or tumor-node-metastasis (TNM) staging among patients with single and double EGFR mutantion. In the double mutation patients treated with EGFR-TKIs, the objective response rate was 36.80%, the disease control rate was 68.40%. The objective response rate was 60.00% and the disease control rate was 90.00% in the patients with single mutation. However, overall PFS was significantly higher in EGFR single mutation patients (P=0.003), with median PFS of 12.0 months compared with 6.0 months in EGFR double mutation patients. CONCLUSIONS There was no significant difference between the clinical features of patients with EGFR double mutation and single mutation. Patients with EGFR double mutation is associated with poor survival underwent the first generation of EGFR-TKIs treatment compared with patients with a single mutation.
Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Exons ; genetics ; Female ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo study the role of interleukin 17 (IL-17) in the pathogenesis of chronic otitis media with effusion (COME).METHODSThe expression of IL-17 in middle ear effusion (MEE) and blood plasma were measured in 30 patients (48 ears) by means of Cytometric Bead Array (CBA), as well as in 20 normal volunteers.RESULTSCompared with the control group, the level of IL-17 significantly increased in the peripheral blood of COME patients (P<0.05). What was more, the level of IL-17 in the MEE was higher than that in peripheral blood of COME patients (P<0.05).CONCLUSIONIL-17, as an important immunoregulatory mediator, may play an important role in chronic course of COME.

Objective:To explore the relationship of CDH17 expression with clinico-pathological features and the correlation be-tween the single nucleotide polymorphisms (SNPs) of CDH17 gene and genetic susceptibility of gastric carcinoma (GC). Methods:A tissue microarray was performed to simulate the dynamic process of invasion and metastasis of GC. Immunohistochemical staining was performed to detect the expression of CDH17 protein, and PCR-based LDR was performed to detect the 2 SNP loci (rs2514813 and rs3214050) genotypes of CDH17 gene. Results: The expression of CDH17 protein in GC was more significantly up-regulated and greatly increased in the intestinal type than in the diffuse type. The expression of CDH17 protein in GC was positively correlated with the histological grading (P<0.01) and was not associated with the survival (P=0.209). With the progression of the cancer invasion, the expression of CDH17 protein in GC showed a downtrend from the gastric mucosa layer to the invasive front edge. The frequencies of the C and T alleles and the CC, CT, and TT genotypes at the CDH17 rs3214050 locus between the GC patients and the control groups were significantly different (P<0.01). However, no significant differences were observed at rs2514813 (P>0.05). The individuals with the T al-leles had longer survival time than those with the CC genotype (P<0.01). Conclusion:The up-regulation of CDH17 expression is in-volved in the maintenance of histological phenotype and progression of GC. Individuals with T alleles at the CDH17 rs3214050 locus have decreased risk of GC and had better prognosis (OR=0.762, 95%CI:0.619-0.937), thereby suggesting that screening for these alleles would help with the assessment of genetic susceptibility and prognosis of GC in the Fujian population.