[A case of nontuberculous mycobacterium presenting as a mass and atelectasis with mediastinal and hilar lymph node enlargement].

With the development of testing technology, the diagnosis of nontuberculous mycobacterium (NTM) lung disease has gradually increased in recent years. Because the clinical characteristics of NTM are not typical, and its imaging manifestations are diverse and nonspecific, missed diagnosis and misdiagnosis are common. Etiological investigation is necessary for diagnosis. Conventional etiological investigations are very limited for the diagnosis of NTM. We reported a case of NTM lung disease presenting with a mass and atelectasis with mediastinal and hilar lymph node enlargement that resembled malignant tumors. The literature on this condition was reviewed to improve the clinician's understanding and broaden clinical thinking.

Comparison of the efficacy and safety of the EC-T (epirubicin/cyclophosphamide followed by docetaxel) and TCb (docetaxel/carboplatin) neoadjuvant regimens in early TOP2A-normal stage II-III breast cancer.

This study aimed to compare the efficacy and safety of the EC-T (4 cycles of epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2, followed by 4 cycles of docetaxel 75 mg/m2) and TCb (6 cycles of docetaxel 75 mg/m2, intravenous drip (ID), day 1 + carboplatin AUC 6, ID, day 1) neoadjuvant regimens in patients with TOP2A-normal stage II-III breast cancer. This study analyzed 280 patients enrolled from three studies registered with ClinicalTrials.gov (NCT03140553, NCT03154749, NCT03507465) with early TOP2A-normal stage II-III breast cancer who received neoadjuvant chemotherapy, including 100 patients who received the EC-T regimen and 180 patients who received the TCb regimen. The primary endpoint was the ratio of RCB 0/1 (residual cancer burden 0/1) after neoadjuvant chemotherapy. The secondary endpoint was the safety of the two groups. There was no significant difference in the ratio of RCB 0/1 between the two groups (23% vs. 23.9%, p=0.614). Among the triple-negative breast cancer patients, the efficacy did not differ between the two groups (40% vs. 32%, p=0.52). Among the lymph node metastasis patients, the efficacy of the EC-T group was significantly better than that of the TCb group (14% vs. 2.6%, p=0.03). Regarding the side effects, the incidence of grade 3/4 anemia was higher in the EC-T group than in the TCb group (21.0% vs. 8.33%, p=0.002), while the incidence of grade 3/4 neutropenia was higher in the EC-T group than in the TCb group (17% vs. 14.44%, p=0.570), and the incidence of grade 3/4 thrombocytopenia was low in each group (EC-T group: 6 % and TCb group: 7.22%, p=0.697). In the EC-T group, grade 3/4 nausea and vomiting occurred in 5 patients. The EC-T group showed a higher rate of grade 3/4 myalgia than the TCb group (7% and 4.44%, respectively, p=0.363). To conclude, the TCb regimen can be used as an alternative regimen for TOP2A-normal stage II-III breast cancer patients in neoadjuvant chemotherapy. However, in patients with node-positive tumors, EC-T is still recommended. Though no difference of grade 3/4 thrombocytopenia in two groups, grade 4 thrombocytopenia caused by the carboplatin-containing regimen should be taken seriously.

[Study on the white matter neuronal integrity in amnestic mild cognitive impairment based on automating fiber-tract quantification].

Objective: To analyze the pattern of the change in cerebral white matter tract in amnestic mild cognitive impairment (aMCI) patients based on the automating fiber-tract quantification (AFQ). Methods: A total of 20 aMCI patients,9 males,11 females, the mean age was (67±9) years, and 22 patients with naMCI, 8 males,14 females, the mean age was (64±10) years, and 23 normal control subjects, 10 males, 13 females, with a mean age of (65±9) years were enrolled from the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2018 to March 2019. All of them underwent 3.0 T MRI scan, which include DTI and 3D T(1)WI sequence.Two tract profiles, fractional anisotropy (FA) and mean diffusivity (MD), were extracted to evaluate the white matter integrity at 100 locations along each of 20 fiber tracts based on the AFQ. Results: In a pointwise comparison of FA profiles,the aMCI patients showed FA reduction in the middle part of right corticospinal tract (t=-4.023, P<0.01, FWE corrected) relative to the naMCI patients. There was a positive correlation between the decreased FA value and the auditory verbal learning test score (P=0.039). In a pointwise comparison of MD profiles, the aMCI patients showed extensive MD elevation in the middle part of the left cingulum hippocampus (t=2.408,P=0.037,FWE corrected) relative to the naMCI patients. The aMCI patients showed MD elevation in the posterior part of the left inferior longitudinal fasciculus (t=-2.919, P=0.006, FWE corrected) and the middle part of the left cingulum hippocampus (t=-3.878, P=0.002, FWE corrected) relative to the NC subjects. And the elevated MD in left inferior longitudinal fasciculus showed negative correlation with MoCA (P=0.039) and auditory verbal learning test score (P=0.015). There was also a negative correlation between the elevated MD value in the left cingulum hippocampus and the auditory verbal learning test score (P=0.033). Conclusions: Disruption is found in specific part along the white matter tract in the aMCI group. Furthermore, the pattern of white matter abnormalities is different across neuronal fiber tracts. These findings will have an impact on the further specific study of the white matter tract in aMCI patients.

[Correlation between spatial navigation disorder and white matter hyperintensity in patients with mild cognitive impairment].

Objective: To investigate the relationship between white matter lesions and spatial navigation ability in patients with mild cognitive impairment (MCI). Methods: A total of 32 MCI patients [age (66±11) years, 16 males and 16 females] who were treated in the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2015 to February 2018 were selected, and matched with age, gender and education level of 28 healthy controls (NC) [age (70±11) years, 19 males and 9 females] underwent spatial navigation ability test and neuropsychology scale evaluation. In the cross-sectional study, all subjects simultaneously underwent 3.0T magnetic resonance three-dimensional liquid inversion recovery sequence and high-resolution T(1) weighted imaging scan. The Wisconsin White Matter Hyperintensities Segmentation Toolbox (W2MHS) was used to automatically mark and extract the volume of the white matter hyperintensity. Results: The average error distances of egocentric virtual (P=0.002) and allocentric virtual (P=0.039) of MCI patients are greater than that of the control group, but the average error distance of mixed (allocentric-egocentric virtual) navigation had no statistic difference between two groups (P=0.070). The volume of the whole white matter hyperintensity, periventricular white matter hyperintensity, and deep white matter hyperintensity showed no significant differences between two groups (all P>0.05). Partial correlation analysis showed that after controlling for age, gender, education level and whole brain volume, the average error distance of mixed (allocentric-egocentric virtual) navigation in MCI patients was positively correlated to the volume of the whole white matter hyperintensity, deep white matter intensity, and periventricular white matter hyperintensity (r=0.469, 0.434, 0.512, all P<0.05). The average error distance of allocentric virtual navigation is positively correlated with the volume of periventricular white matter hyperintensity (r=0.403, P=0.033). There is no correlation between the average error distance of egocentric virtual navigation and the hyperintensity of white matter. Conclusions: The spatial navigation ability of patients with MCI is related to white matter lesions, which is of great significance for further research on the potential biological mechanisms affecting human spatial navigation ability.

[The therapeutic effect of carnosine combined with dexamethasone in the lung injury of seawater-drowning].

Objective: To explore the therapeutic effect of carnosine and dexamethasone in lung injury caused by seawater drowning. Methods: The in vitro experiments with A549 cells were divided into 5 groups: blank control group (C), seawater injury group (S), seawater injury+dexamethasone treatment group (S+D), seawater injury+carnosine treatment group (S+C), seawater injury dexamethasone and carnosine combined therapy(S+D+C) group. The optimal therapeutic dose of drugs for the treatment of seawater drowning lung injury was tested in vitro. Based on the optimal dose, the levels of TNF-α and IL-6 in each group at different time points were detected at the cell level by ELISA. The level of apoptosis was detected by flow cytometry. The in vivo experiments with SD rats were randomly divided into 5 groups (n=8 each): blank control group (RC),seawater drowning injury group (RS),seawater drowning injury+dexamethasone treatment group (RSD),seawater drowning injury+carnosine treatment group (RSC),seawater drowning injury+dexamethasone+carnosine combined treatment group (RSDC). The animal model with seawater inhalation acute lung injury was made by intratracheal infusion (4 ml/kg). The pathological changes of the lungs were observed. The expression of superoxide dismutase (SOD) in each group was detected by Western blot. Results: The results of in vitro experiments showed significant increase of apoptosis after seawater injury. The normal cell rate in group C was 98.3% while the apoptosis rate was 1.7%. The normal cell in group S was 18.8%, and the apoptosis rate was 81% (P<0.01). TNF-α and IL-6 levels in group S increased to 180.25 ng/L and 61.56 ng/L, respectively, which were statistically significant compared with group C (P<0.01). After drug protection, apoptosis was reduced in S+D group, S+C group and S+D+C group, with apoptosis rates of 65.4%, 70.9% and 42.6%, respectively. The contents of TNF-α and IL-6 also decreased in the S+D+C group (P<0.01). The results of in vivo experiments showed obvious lung injury and disordered lung tissue structures in the RS group at 4 h after modeling. There was hemorrhage in the pulmonary interstitium and a large number of inflammatory cells. Results of western blot showed that the expression of SOD increased in the RS group. Compared with RS group, the treatment alleviated acute lung injury and decreased the expression level of SOD in RSD, RSC and RSDC groups (P<0.01). Conclusion: Dexamethasone and carnosine reduced the influence of seawater inhalation on the lung in the rat model. The positive effect of combination of these two drugs on lung injury caused by seawater inhalation was stronger than a single drug.

[Diagnostic value of endobronchial ultrasonography with guide-sheath combined with virtual bronchoscopy navigation in peripheral lung cancer].

Objective: To explore the diagnostic value and safety of endobronchial ultrasonography with guide-sheath (EBUS-GS) combined with virtual bronchoscopy navigation (VBN) in peripheral lung cancer. Methods: Between Dec. 2015 to Dec. 2016, patients with pulmonary solitary nodule suspected of early lung cancer on computed tomography (CT) in Department of Respiratory, Tangdu Hospital, Fourth Military Medical University were enrolled for this study. The patients underwent EBUS-GS transbronchoscopic lung biopsy (TBLB) with or without VBN. The visibility rate, diagnostic yield, influencing factors, the operation time and complications were evaluated in the 2 groups. The data were compared using independent sample t test or chi-squared test. Results: A total of 134 patients were enrolled and completed this study. Among them 74 were males and 60 were females. There were 64 cases in the group of EBUS-GS with VBN (VBNA), and 70 in the group without VBN (NVBNA). The visibility rate and diagnosis rate of VBNA group were 87.5% (56/64) and 78.1% (50/64), respectively. The mean time of operation and confirming the target lesions were (25±5), (5.8±1.3) min, respectively. The visibility rate and diagnosis rate of NVBNA group were 81.4%(57/70) and 75.7%(53/70), respectively. The mean time of operation and confirming the target lesions were (27±6), (9.8±1.5)min .There was no significant difference in the visibility rate and diagnosis rate between the 2 groups (χ(2)=0.933, P=0.334; χ(2)=0.109, P=0.838). There was no significant difference in the mean operation time between the 2 groups(t=0.633, P=0.524). But the time of confirming the target lesions between the 2 groups was statistically different (t=17.41, P<0.01). EBUS-GS-TBLB was well tolerated. No severe complications such as pneumothorax or chest pain were observed. There were 3 patients in the VBNA group and 7 patients in the NVBNA group experiencing a small amount of biopsy site bleeding. The incidence of complications did not differ between the 2 groups(χ(2)=1.366, P=0.330). Conclusions: VBN could not improve the diagnostic yield of EBUS-GS. However, it could shorten the time needed to confirm the target lesions and did not increase the incidence of EBUS-GS complications, indicating that EBUS-GS with VBN was a safe and effective method.

[Study on age and white matter neuronal integrity in healthy volunteers based on automating fiber-tract quantification].

Objective: To analyze age-related change in cerebral matter tract, especially fractional anisotropy, based on automating fiber-tract quantification(AFQ). Methods: A total of 64 years old normal persons and 43 young volunteers were enrolled respectively from the Affiliated Drum Tower Hospital of Nanjing University Medical School and community from January 2015 to June 2016.All of them underwent MRI scan, which included DTI and 3D T(1)WI sequence .All cases were divided into 3 groups according to their ages, the young group 20-35 years old, the middle old group 60-75 years old, the old group 76-90 years old.AFQ was used to identify 20 major white matter tracts in brains of all subjects and make measurements at anatomically equivalent locations along their trajectories. Results: The FA change trend of each fiber was similar among three groups. The old and the middle old group had different FA value in both sides of inferior fronto-occipital fasciculus(left t=-2.73, right t=-6.12, P<0.05), thalamic radiation(left t=-4.79, right t=-19.61, P<0.05), arcuate(left t=10.53, right t=-2.72, P<0.05), callosum forceps(genu t=-2.66, splenium t=28.64, P<0.05), cingulum(left t=-4.53, right t=-2.22, P<0.05)and right corticospinal tract(t=3.10, P<0.05), among which each location of callosum forceps minor was different between the old group and the young group, and this area decreased in the middle group. The old group had different FA value in both sides of uncinate fasciculus(left t=-4.52, right t=-4.53, P<0.05), left corticospinal tract(t=-2.19, P<0.05)and right inferior longitudinal fasciculus(t=11.12, P<0.05). Compared to the young group, there was no statistical difference in the FA of both superior longitudinal fasciculus and left inferior longitudinal fasciculus in the old and the middle old group. Conclusion: AFQ has an impact on the further specific study of the age-related white matter tract.

[Change of white matter neuronal integrity associated with spatial navigation impairment in mild cognitive impairment].

Objective: To analyze the correlation between white matter integrity and spatial navigation impairment in patients with mild cognitive impairment (MCI). Methods: A total of 27 MCI subjects and 24 healthy controls were enrolled from the Affiliated Drum Tower Hospital of Nanjing University Medical School from May 2015 to February 2016, who underwent 3.0 T MRI scan and 2D-computer version spatial navigation test.DTI preprocessing and tract-based spatial statistics (TBSS) were performed by PANDA.Two sample t-test and partial correlation coefficients were performed to investigate the correlation of white matter impairments and spatial navigation decline. Results: Relative to controls, MCI showed worse egocentric navigation (t=-2.202, P<0.05). Decreased FA in superior longitudinal fasciculus (left t=2.95, right t=2.95, P<0.05), inferior longitudinal fasciculus and inferior fronto-occipital fasciculus (left t=2.66, right t=2.96, P<0.05), corpus callosum (t=2.09, P<0.05), cingulum (left t=2.76, right t=2.41, P<0.05), fornix (t=4.83, P<0.05), and corticospinal tract (left t=2.33, right t=2.26, P<0.05), were found in the MCI subjects.The decreased FA value of superior longitudinal fasciculus (left r=-0.354, right r=-0.347, P<0.05), inferior longitudinal fasciculus (left r=-0.338, right r=-0.336, P<0.05), cingulum (left r=-0.395, right r=-0.370, P<0.05), right corticospinal tract (r=-0.362, P<0.05) and fornix (r=-0.369, P<0.05) were correlated with increased ego average total error.Allo average total error were negative correlated with FA value of superior longitudinal fasciculus (left r=-0.329, right r=-0.350, P<0.05), inferior longitudinal fasciculus (left r=-0.349, right r=-0.378, P<0.05), splenium of corpus callosum (r=-0.364, P<0.05) and cingulum (left r=-0.340, right r=-0.406, P<0.05). Conclusion: This study implicated the potential white matter structural basis of spatial navigation impairment and will have an impact on the further study of the neurobiological mechanisms of human spatial navigation ability.

Overexpression of Arabidopsis HsfA1a enhances diverse stress tolerance by promoting stress-induced Hsp expression.

Arabidopsis (Arabidopsis thaliana) group A1 heat shock factors (Hsfs), including HsfA1a, are important regulators in the heat shock response. Previous studies have revealed that genetically engineered HsfA1 members result in constitutive Hsf activation and heat shock protein gene (Hsp) expression under normal conditions, eventually enhancing basic thermotolerance in transgenic plants. In this study, we generated transgenic Arabidopsis plants overexpressing HsfA1a. One transgenic line showed a 94-fold increase in the level of HsfA1a mRNA (OE line 1). Overexpressing HsfA1a in OE line 1 plants resulted in higher levels of the inducible expression of Hsp18.2 and Hsp70 genes in response to heat stress, low/high pH changes, and hydrogen peroxide. Analysis of in vivo HsfA1a-promoter binding suggested that the higher level of inducible Hsp expression was mediated by stress-induced activation of elevated levels of HsfA1a in the OE plants. The OE plants showed an increase in tolerance to low/ high pH changes and hydrogen peroxide, in addition to heat shock. These results revealed that overexpressing HsfA1a had positive effects on tolerance to diverse stressors by promoting inducible Hsp expression following stress-induced HsfA1a activation. This study suggests a different mechanism for the activation of genetically engineered Hsfs from that suggested in previous reports, thus providing new insight into complex mechanisms used for achieving stress tolerance by genetic engineering.

Effects of short-term sitagliptin treatment on immune parameters in healthy individuals, a randomized placebo-controlled study.

Sitagliptin, a dipeptidyl-peptidase 4 (DPP-4) inhibitor, improves blood glucose control in patients with type 2 diabetes by blocking cleavage of glucagon-like peptide 1 (GLP-1). In type 2 diabetes patients sitagliptin use is associated with an increase in minor infections, and in new-onset type 1 diabetes patients the ability of sitagliptin to dampen autoimmunity is currently being tested. DPP-4, also known as CD26, is expressed on leucocytes and can inactivate many chemokines important for leucocyte migration, as well as act as a co-stimulatory molecule on T cells. Therefore, this study was conducted to test whether sitagliptin is immunomodulatory. In this randomized, placebo-controlled trial, healthy volunteers were given sitagliptin or placebo daily for 28 days, and blood was drawn for immune assays. No significant differences were observed in the percentage of leucocyte subsets within peripheral blood mononuclear cells (PBMCs), plasma chemokine/cytokine levels or cytokines released by stimulation of PBMCs with either lipopolysaccharide (LPS) or anti-CD3. Individuals taking sitagliptin displayed increases in the percentage of cells expressing higher levels of CD26 at early time-points compared to placebo controls, but these differences resolved by day 28 of treatment. Therefore, in healthy volunteers, treatment with sitagliptin daily for 28 days does not overtly alter systemic immune function.

[Endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma].

Objective: To describe a technique of endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma, based on anatomic studies and surgeries. Methods: Three dry human skulls and five fresh human cadaver heads were used for anatomic study of a endoscopic transoral approach to expose petroclival and jugular foramen. The anatomical landmarks and the extent of exposure were recorded. Six clinical cases who were treated in Eye & ENT Hospital, Fudan University from June 2020 to April 2022 were used to illustrate the technique and feasibility of this approach and to assess its indications and advantages, including 3 males and 3 females, aged 42 to 69 years old. Descriptive analysis was used in this research. Results: On the basis of the preservation of the internal pterygoid muscle and the external pterygoid muscle, this approach could fully expose the parapharyngeal, petrosal and paraclival segment internal carotid arteries, and safely deal with the lesions of jugular foramen and petroclival region. The 6 patients in our study tolerated the procedure well. Postoperative enhanced MRI showed complete resection of the tumor and no postoperative masticatory dysfunction. Conclusion: Endoscopic transoral approach is a safe, minimally invasive and effective surgical treatment for petroclival and jugular foramen recurrent nasopharyngeal carcinoma.

[Safety and efficacy of proximal gastrectomy with double tract anastomosis reconstruction for upper gastric cancer: a meta-ananlysis].

Objective: It is not yet to be clarified whether proximal gastrectomy with double tract anastomosis reconstruction (PG-DT) for gastric cancer increases postoperative complications. This meta-analysis aims to evaluate the safety and efficacy of PG-DT for upper gastric cancer. Methods: The Chinese and English literatures about PG-DT and total gastrectomy with Roun-en-Y digestive tract reconstruction (TG-RY) for upper gastric cancer were searched from PubMed, Embase, Cochrane Library, Wiley Online Library, Web of Science, CNKI net, Wanfang database and VIP database. Literature inclusion criteria: (1) prospective or retrospective cohort study of PG-DT and TG-RY for upper gastric cancer published publicly; (2) patients with upper gastric cancer; (3) the enrolled literatures included at least one of the following outcome indicators: operation time, intraoperative blood loss, postoperative exhaust time, postoperative feeding time, hospitalization time, number of harvested lymph nodes, postoperative complications, postoperative 1-year albumin, postoperative 1-year hemoglobin and 1-, 3-, 5-year survival after surgery. Literature exclusion criteria: (1) reviews, case reports, conference summaries and other non-control studies; (2) studies published repeatedly, studies with incomplete or unextractable information. The search time ended in February 2021. The basic information and evaluation indicators included in the article were extracted. The retrospective study was evaluated using Newcastle-Ottawa literature quality evaluation scale. The prospective randomized controlled study was evaluated using Jadad modified scale. Meta-analysis was performed using Review Manager 5.3. Publication bias was assessed using funnel map. Publication bias was tested using Egger tools. Results: A total of 385 literatures were searched, finally 2 randomized controlled trials and 16 retrospective cohort study were included. There were 1521 patients, including 692 in the PG-DT group and 829 in the TG-RY group. The meta-analysis of the enrolled indicators showed that as compared to TG-RYT group, PG-DT group had less intraoperative blood loss (OR=-54.58, 95%CI: -57.77 to -51.38, P<0.001), shorter postoperative exhaust time (OR=-0.21, 95%CI: -0.29 to -0.13, P<0.001), shorter hospitalization time (OR=-0.98, 95%CI: -1.31 to -0.64, P<0.001), less harvested lymph nodes (OR=-6.07, 95%CI: -7.14 to -4.99, P<0.001), lower morbidity of postoperative complication (OR=0.32, 95%CI: 0.24 to 0.43,P<0.001), higher level of postoperative 1-year albumin (OR=1.90, 95%CI: 1.08 to 2.77, P<0.001) and postoperative 1 year hemoglobin (OR=5.07, 95%CI: 2.83 to 7.31, P<0.001). While there were no significant differences in operation time (OR=0.08, 95%CI: -4.24 to 4.39, P=0.97), postoperative feeding time (OR=-0.05, 95%CI: -0.15 to 0.06, P=0.39), 1-year survival after surgery (OR=1.61, 95%CI: 0.69 to 3.75, P=0.27), 3-year survival after surgery (OR=1.31, 95%CI: 0.81 to 2.10, P=0.27) and 5-year survival after surgery (OR=1.50, 95%CI: 0.86 to 2.63, P=0.15) between two groups. Conclusions: PG-DT treatment for upper gastric cancer is safe and feasible. Compared with TG-RY, PG-DT has advantages in intraoperative bleeding, postoperative exhaust time, hospitalization time, morbidity of postoperative complication and postoperative nutritional indicators.

[Analysis of clinical prognosis of endoscopic salvage surgery in patients with rT2 recurrent nasopharyngeal carcinoma].

Objective: To investigate the feasibility of endoscopic salvage surgery for patients with rT2 recurrent nasopharyngeal carcinoma (rNPC) and to analyze their prognostic factors. Methods: The clinical data of 33 patients with rT2 rNPC who underwent endoscopic extended nasopharyngectomy in Eye & ENT Hospital Affiliated to Fudan University from January 2015 to July 2020 were analyzed, including 29 males (87.9%) and 4 females (12.1%), aging (51.7±10.6) years. The clinicopathological characteristics of these patients were recorded and analyzed, in terms of gender, sex, alcohol and cigarette use, interval between primary treatment to recurrence, adjuvant therapy, lymph node metastasis, internal carotid artery (ICA) invasion, necrosis, margin and reconstruction materials. Kaplan Meier analysis was used to plot the overall survival rate and progression free survival rate curve, Log-rank test was used to analyze the prognostic factors among patients, and multivariate Cox proportional hazards regression was used to determine the independent risk factors of tumor progression free survival. Results: Among 33 patients with rT2 rNPC, the recurrence interval of 24 patients with rNPC after primary radiotherapy was more than 2 years. A total of 25 patients received primary radiotherapy and adjuvant chemotherapy at the same time. There were 6 cases with cervical lymph node metastasis, 12 cases with ICA invasion, 8 cases with positive surgical margin, 7 cases underwent ICA embolization before operation. A total of 18 cases underwent pedicled tissue flap repairment after operation, including 12 pedicled nasal septal mucosa flaps and 6 temporalis muscle flaps. The median follow-up time was 15 months. Five patients died because of disease progression (in 2 cases), post surgical ICA hemorrhage (in 1 case), liver metastasis (in 1 case) and dysphagia (in 1 case). The 1-year, 2-year and 3-year overall survival rates of all patients were 93.9%, 81.8% and 81.8%, respectively. The 1-year, 2-year and 3-year progression free survival rates were 74.7%, 59.7% and 40.9%, respectively. Log-rank statistical analysis showed that the positive surgical margin (P=0.060) and recurrence interval (P=0.151) were possibly related to the prognosis of rT2 rNPC. Multivariate Cox regression analysis showed that the positive surgical margin was an independent risk factor for patients with rT2 rNPC (P=0.034). Nasopharynx hemorrhage occurred in 4 patients, skull base bone necrosis occurred in 2 patients, trismus occurred in 3 patients, and no obvious brain complications occurred in 7 patients with ICA embolization. Conclusion: Endoscopic salvage surgery for rT2 rNPC is a safe and effective surgical option, but the long-term effect still needs long-term follow-up in bulk cases.

[The application of temporalis muscle flap in the salvage nasopharyngectomy for advanced recurrent nasopharyngeal carcinoma].

Objective: To summarize the application of temporalis muscle flap in the salvage nasopharyngectomy for advanced recurrent nasopharyngeal carcinoma (rNPC), and to provide guidance for the repair of extensive skull base defects in salvage rNPC. Methods: A total of 54 patients with the application of temporalis muscle flap in the salvage nasopharyngectomy for advanced rNPC were retrospectively analyzed, including 42 males and 12 females, aging from 29 to 71 years. There were 36 patients with rT3 and 18 patients with rT4. The surgical methods of temporalis muscle flap repair were summarized. The general situation, survival time and postoperative complications of patients were recorded, and the advantages and disadvantages of temporalis muscle flap were discussed. Results: The temporal muscle flap could completely cover the defect area of nasopharynx and skull base, without the need for other autologous repair materials. The follow-up period was 2 to 28 months. The survival rate of temporalis flap was 98.1% (53/54). The 1-year overall survival rate was 84.5% while 1-year progression-free survival rate was 49.0%. None of the patients had facial nerve injury. Three patients (5.6%) had necrosis of the cranial membrane required surgical intervention and four patients (7.4%) required a chonoplasty due to severe chonostril stenosis or chonostril atresia. Eleven cases (20.4%) had mouth opening restriction, chewing weakness, dysphagia and other eating difficulties. Conclusions: Temporalis muscle flap is an alternative flap for the salvage nasopharyngectomy for advanced rNPC. Temporal muscle flap shows high survival rate and wide coverage, but the surgeon should apprehend the possible complications and reduce the occurrence of them.

[Internal carotid artery embolization in endoscopic salvage surgery for recurrent nasopharyngeal carcinoma: a single-center retrospective study].

Objective: To evaluate the efficiency of internal carotid artery (ICA) embolization technology in endoscopic salvage surgery for recurrent nasopharyngeal carcinoma (rNPC) invading the ICA. Methods: From January 2016 to March 2021, 83 patients with rNPC who invaded the ICA and underwent endoscopic extended nasopharyngectomy were retrospectively collected from the Eye & ENT Hospital in Fudan University, including 60 males and 23 females. The age of the patients ranged from 27 to 77 years. The standard of ICA invasion was that the distance from the lesion to the ICA on enhanced MRI was ≤ 1.8 mm. The clinical characteristics, ICA management strategy and survival prognosis of patients were analyzed, and the effectiveness of ICA embolization was evaluated. Kaplan-Meier method was used to calculate the survival rate and Log-rank test was used to compare the difference. Results: In 83 patients with rNPC, there were 13 patients with rT2, 38 patients with rT3, 32 patients with rT4, and 16 patients had lymph node metastasis. A total of 37 patients (44.6%) underwent ICA coil embolization before surgery, of which 2 cases underwent external carotid-middle cerebral artery artery bypass grafting and ICA embolization due to positive balloon occlusion test (BOT). Patients with positive surgical margin accounted for 24.1% (20/83). Among them, patients with rT4 and patients without ICA embolization had a higher positive rate of surgical margin (P value was 0.001, 0.043, respectively). The 3-year overall survival (OS) and progression free survival (PFS) rate of all patients was 46.5% and 26.7%, respectively. In addition, the 3-year OS and PFS of patients with ICA embolization was significantly higher than those without ICA embolization, respectively (69.1% vs 27.8%, P=0.003; 33.9% vs 18.9%, P=0.018). Only 2 patients (2/37, 5.4%) had cerebral infarction complications after coil embolization of the affected ICA due to negative BOT. Conclusion: Preoperative ICA embolization can be used to treat patients with rNPC invading the ICA, improve the total removal rate and survival rate of patients, which is an effective salvage treatment.

Identification of caveolin-1 in lipoprotein particles secreted by exocrine cells.

Caveolin-1 is a protein component (of relative molecular mass 22, 000) of the striated coat that decorates the cytoplasmic surface of caveolae membranes. Previous biochemical and molecular tests have indicated that caveolin-1 is an integral membrane protein that is co-translationally inserted into endoplasmic-reticulum membranes of fibroblast and epithelial cells such that its carboxy- and amino-terminal ends are in the cytoplasm. Here we identify caveolin-1 in the secretory pathway of exocrine cells. Secretion of caveolin-1 from pancreatic acinar cells and a transfected exocrine cell line, but not from Chinese hamster ovary cells, is stimulated by the secretagogues secretin, cholecystokinin and dexamethasone. The secreted caveolin-1 co-fractionates with apolipoproteins, indicating that it may be secreted in a complex with lipids.

Inhibition of interleukin 2 signaling and signal transducer and activator of transcription (STAT)5 activation during T cell receptor-mediated feedback inhibition of T cell expansion.

Limitation of clonal expansion of activated T cells is necessary for immune homeostasis, and is achieved by growth arrest and apoptosis. Growth arrest and apoptosis can occur passively secondary to cytokine withdrawal, or can be actively induced by religation of the T cell receptor (TCR) in previously activated proliferating T cells. TCR-induced apoptosis appears to require prior growth arrest, and is mediated by death receptors such as Fas. We tested whether TCR religation affects T cell responses to interleukin (IL)-2, a major T cell growth and survival factor. TCR ligation in activated primary human T cells blocked IL-2 induction of signal transducer and activator of transcription (STAT)5 DNA binding, phosphorylation of STAT5, Janus kinase (Jak)1, Jak3, and Akt, and kinase activity of Jak1 and Jak3. Inhibition was mediated by the mitogen-activated protein kinase kinase (MEK)-extracellular stimulus-regulated kinase (ERK) signaling pathway, similar to the mechanism of inhibition of IL-6 signaling we have described previously. TCR ligation blocked IL-2 activation of genes and cell cycle regulatory proteins, and suppressed cell proliferation and expansion. These results identify TCR-induced inhibition of IL-2 signaling as a novel mechanism that underlies antigen-mediated feedback limitation of T cell expansion, and suggest that modulation of cytokine activity by antigen receptor signals plays an important role in the regulation of lymphocyte function.

[Efficacy and safety of pylorus-preserving gastrectomy for early gastric cancer located in the middle third of the stomach: a meta-analysis].

Objective: It is yet to be clarified whether pylorus-preserving gastrectomy (PPG) for early gastric cancer will bring the risk of radical tumor resection, whether it will increase the incidence of postoperative complications, and how much is the benefit of the quality of life for patients after surgery, these issues are not clear. This meta-analysis aims to evaluate the efficacy and safety of pylorus-preserving gastrectomy (PPG) for early middle gastric cancer. Methods: The Chinese and English literatures about PPG and distal gastrectomy (DG) for early gastric cancer were searched from PubMed, Embase, The Cochrane Library, Web of Science, CNKI net and Wanfang database. Literature inclusion criteria: (1) Prospective or retrospective cohort study of PPG and DG for early middle-third gastric cancer published publicly; (2) Patients with early middle-third gastric cancer; (3) The enrolled literatures include at least one of the following outcome indicators: the efficacy indicators include gallstone, residual gastritis, bile reflux, delayed gastric emptying, dumping syndrome, reflux esophagitis and overall complication; the long-term prognostic indicators include 5-year survival rate and 5-year tumor recurrence. Literature exclusion criteria: (1) Reviews, case reports, conference summaries and other non-control studies; (2) Repeated published studies, incomplete studies and unextractable studies; (3) The depth of tumor invasion exceeding submucosa. The search time ended in July 2020. The basic information and evaluation indicators included in the article were extracted. The retrospective study was evaluated using Newcastle-Ottawa literature quality evaluation scale. The prospective randomized controlled study was evaluated using Jadad modified scale. Meta-analysis was performed using Review Manager 5.3. Publication bias was assessed using funnel map. Publication bias was tested using Egger tools. Results: A total of 717 literatures were retrieved, and 17 literatures were enrolled finally, including 2 randomized controlled trials and 15 retrospective studies. A total of 2427 patients were enrolled, including 948 in PPG group and 1479 in DG group. The meta-analysis of the efficacy indicators showed that there were significant differences in gallstones incidence (OR=0.42, 95% CI: 0.28-0.65, P<0.001), residual gastritis incidence (OR=0.50, 95% CI: 0.32-0.77,P=0.002), bile reflux incidence (OR=0.30, 95% CI: 0.20-0.45, P<0.001), delayed gastric emptying incidence (OR=2.40, 95% CI:1.67-3.45, P<0.001), and postoperative dumping syndrome incidence (OR=0.28, 95% CI: 0.15-0.51, P<0.001), while there were no significant differences in postoperative overall complications (OR=0.97, 95% CI: 0.69-1.35, P=0.840), reflux esophagitis incidence (OR=0.79, 95% CI: 0.39-1.61, P=0.520) between the two groups. The meta-analysis of the long-term prognostic indicators showed that no significant differences of 5-year survival (OR=1.02, 95% CI: 0.61-1.71, P=0.940) or 5-year tumor recurrence (OR=0.77, 95% CI: 0.36-1.68, P=0.520) were observed between the two groups. Conclusion: The incidences of gallstone, residual gastritis, dumping syndrome, bile reflux are lower after PPG in early gastric cancer, while the postoperative overall complications and long-term survival are comparable between PPG and DG, indicating that PPG is quite safe and feasible.

[Clinical analysis of sinonasal chondrosarcoma in 47 cases].

Objective: To discuss the treatment, pathological subtypes and recurrence of sinonasal chondrosarcoma, and to identify the prognostic factors. Methods: Between January 1994 and May 2018, 47 patients with sinonasal chondrosarcoma who were treated in Eye, Ear, Nose and Throat Hospital, Shanghai Medwal College, Fudan University were retrospectively reviewed, including 19 males and 28 females, aging from 7 months to 71 years old, with a median age of 38 years old. The clinical symptoms, location of tumor, surgical method, pathological subtype, recurrence and prognosis were collected and analyzed. Kaplan-Meier method was used to calculate the disease-specific survival rate, disease-free survival rate and draw survival curve. Log Rank was used to analyze the prognostic factors. Cox regression was used for multivariate analysis. Results: Except for one patient who gave up treatment after tumor biopsy, other 46 patients underwent radical resection, including 31 cases of endoscopic resection and 15 cases of extranasal approach resection. Thirty-nine patients were diagnosed as conventional intramedullary chondrosarcoma with pathological grade Ⅰ of 24 cases and grade Ⅱ of 15 cases. Six cases were diagnosed as mesenchymal chondrosarcoma while 2 cases were diagnosed as myxoid chondrosarcoma. During an average follow-up period of 56.1 months (17-156 months), 23 patients had recurrence (54.8%, 23/42), among whom 9 patients had re-operations and 5 patients died. Thirty-seven patients survived, including 25 patients survived without tumors. In addition, 5 patients were lost to follow-up, including the patient who gave up treatment after tumor biopsy. Five-year overall survival rate and disease-free survival rate was 84.7% and 34.3%, respectively. Multivariate analysis showed that invasion of skull base was an independent risk factor affecting disease-free survival rate (95% confidence interval: 1.089-5.825, P=0.031). Conclusions: Radical resection is the primary treatment for sinonasal chondrosarcoma. The most common pathological subtype is conventional intramedullary chondrosarcoma. Sinonasal chondrosarcoma has a high local recurrence rate. The long-term prognosis is well after complete excision of the lesion. The most important cause of death is uncontrollable local disease and invasion of adjacent key structures.