Piezo1 channel activation facilitates baroreflex afferent neurotransmission with subsequent blood pressure reduction in control and hypertension rats.

Mechanosensitive cation channels such as Piezo1 and Piezo2 are activated by mechanical force like a starched wall of the aorta while blood pressure (BP) rising, which helps to elucidate the underlying mechanism of mechanotransduction of baroreceptor endings. In this study we investigated how Piezo1 channel activation-mediated gender- and afferent-specific BP regulation in rats. We established high-fat diet and fructose drink-induced hypertension model rats (HFD-HTN) and deoxycorticosterone (DOCA)-sensitive hypertension model rats. We showed that the expression levels of Piezo1 and Piezo2 were significantly up-regulated in left ventricle of HFD and DOCA hypertensive rats, whereas the down-regulation of Piezo1 was likely to be compensated by Piezo2 up-regulation in the aorta. Likewise, down-regulated Piezo1 was observed in the nodose ganglion (NG), while up-regulated Piezo2 was found in the nucleus tractus solitarius (NTS), which might synergistically reduce the excitatory neurotransmitter release from the presynaptic membrane. Notably, microinjection of Yoda1 (0.025-2.5 mg/ml) into the NG concentration-dependently reduced BP in both hypertensive rat models as well as in control rats with similar EC50; the effect of Yoda1 was abolished by microinjection of a Piezo1 antagonist GsMTx4 (1.0 µM). Functional analysis in an in vitro aortic arch preparation showed that instantaneous firing frequency of single Ah-fiber of aortic depressor nerve was dramatically increased by Yoda1 (0.03-1.0 µM) and blocked by GsMTx4 (1.0 µM). Moreover, spontaneous synaptic currents recorded from identified 2nd-order Ah-type baroreceptive neurons in the NTS was also facilitated over 100% by Yoda1 (1.0 µM) and completely blocked by GsMTx4 (3.0 µM). These results demonstrate that Piezo1 expressed on Ah-type baroreceptor and baroreceptive neurons in the NG and NTS plays a key role in a sexual-dimorphic BP regulation under physiological and hypertensive condition through facilitation of baroreflex afferent neurotransmission, which is presumably collaborated by Piezo2 expression at different level of baroreflex afferent pathway via compensatory and synergistic mechanisms.

Efficacy and safety of esophagectomy via left thoracic approach versus via right thoracic approach for middle and lower thoracic esophageal cancer: a multicenter randomized clinical trial (NST1501).

Background: Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC). Methods: Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test. Results: A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92 vs. 205.34±51.47 min, P<0.001); had more complications (33.8% vs. 26.3% P=0.016); harvested more lymph nodes (LNs) (23.61±10.09 vs. 21.92±10.26, P=0.015); achieved a significantly improved OS in stage IIIa patients (67.8% vs. 51.8%, P=0.022). The 3-year OS and DFS were 68.7% and 64.3% in LTA arm versus 71.3% and 63.7% in RTA arm (P=0.20; P=0.96). Conclusions: Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy. Trial Registration: ClinicalTrials.gov NCT02448979.

Wide Gastric Conduit Increases the Risk of Benign Anastomotic Stricture After Esophagectomy.

BACKGROUND: To identify the association between the width of the gastric conduit and the benign anastomotic stricture (BAS) after esophagectomy with end-to-side cervical anastomosis for esophageal cancer. METHODS: Patients with esophageal cancer who underwent esophagectomy between July 2013 and July 2014 were included in this study. The gastric conduit was used for reconstruction in all patients and end-to-side cervical anastomosis were performed using a circular stapler. The patients were divided into a narrow group (3-5 cm) and a wide group (>5 cm) based on the gastric conduit width. Univariate and multivariate logistic regressions were used to analyze the possible factors (patients' age, gender, preoperative comorbidities, neoadjuvant chemotherapy, gastric conduit width, anastomotic leakage) that could affect the incidence of BAS. RESULTS: Two-hundred and one patients were included in this study. The median follow-up period was 29 months (17-58 months). Seven cases (3.5%) showed anastomotic leakage in the postoperative period and 38 patients (18.9%) developed BAS; all within the first year of follow-up. In univariate analysis, the width of the gastric conduit was the only risk factor for the development of BAS (odds ratio [OR] = 3.36, P = .005). In multivariate logistic regression analysis, the wide group was an independent significant risk factor for the development of BAS developing compared with the narrow group (OR = 2.84, P = .02). CONCLUSIONS: A wide gastric conduit width (>5 cm) is an independent risk factor for the development of BAS after esophagectomy and stapled cervical end-to-side anastomosis for esophageal cancer.

[Clinical features and management of pyothorax due to postoperative cervical anastomotic leakage in esophageal cancer surgery].

OBJECTIVE: To investigate the clinical characteristics and managements of pyothorax due to postoperative cervical anastomotic leakage after esophageal cancer surgery. METHODS: From January 2006 to January 2013, 3342 patients with esophageal carcinoma underwent esophagectomy and cervical esophagogastric anastomosis. Of them, 19 patients developed pyothorax following cervical anastomotic leakage and their clinicopathological data were analyzed retrospectively. RESULTS: All the patients underwent a cervical anastomosis via a three-incisional approach (right cervicothoracic mid-abdominal incision, RT group, n=1094) or a two-incisional approach (left cervicothoracic incision, LT group, n=2248). The total number of cervical anastomotic leakage cases was 237, of which 152 cases were in LT group (6.8%), and 85 cases in RT group (7.8%), respectively (P=0.287). The incidence of pyothorax was 2.0% (n=3) in LT group, and 18.8% (n=16) in RT group, respectively (P<0.01). Fourteen cases develop pyothorax within 3 days after operation. The main symptoms were high fever, dyspnea and chest pain. All the pyothorax patients received conservative treatments, including thoracic closed drainage, nasogastric tube placement, jejunal stoma, nutritional support, antibiotics and symptomatic treatment. Sixteen cases were cured, while 3 cases were dead. CONCLUSIONS: The right thoracotomy approach predisposes the cervical anastomotic leakage-associated pyothorax. Sufficient drainage and sufficient nutritional support are critical to the treatment.

[Prevalence and surgical status of cataract among adults aged 50 years or above in rural Jiangsu Province].

OBJECTIVE: To survey the prevalence, operative status, surgical coverage rate and social burden rate of cataract blindness among older adults aged 50 years or above in 2 typical counties (district) of Jiangsu Province, China in 2010. METHODS: Cluster sampling was used in randomly selected 12 867 individuals aged 50 years or above in 58 clusters in Funing County of Northern Jiangsu and Binhu District of Southern Jiangsu. Among them, 12 053 individuals received visual acuity and eye examinations (response rate 93.8%). Lens and cataract operative status were evaluated by slit-lamp biomicroscope. Data bank was established by Epidata3.0 Software. Statistical analyses were performed with Stata/SE Statistical Software, version 10.0. Confidence intervals and P values (significant at P < 0.05) for prevalence of cataract, surgical coverage rate of cataract, social burden rate and surgical outcomes of cataract blindness were calculated with adjustment for clustering effects and stratification associated with the sampling design. RESULTS: Among 12 503 individuals, there were 2208 cases of cataract with a prevalence of 18.3%. The prevalence of cataract was higher in the aged, female and lower-income persons (P < 0.05). Among 2208 cataract patients, cataract surgery was performed in 263 cases (11.9%). The surgical coverage rate of cataract was 59.7% and the social burden rate of cataract blindness 1.93%. The social burden rate of cataract blindness was higher in the aged persons (P < 0.01). In 357 eyes with cataract surgery, the rate of intraocular lens implantation was 85.7%. At Binhu, 71.0% of eyes with cataract surgery underwent phacoemulsification. At Funing, 73.6% of eyes underwent modern extra-capsular surgery respectively. Post-operative presenting and best corrected visual acuity over 0.7 was 11.2% and 19.6% of operated eyes respectively. The main causes of post-operative eyes with worse visual acuity (< 0.3) were post-capsular opacity and retinal disorders. CONCLUSION: Cataract is the most common and important eye disease that may lead into blindness and severe visual impairment among older adults aged 50 years or above. The coverage rate of cataract surgery is higher in Jiangsu province than in other provinces. The visual outcomes of surgery is less than ideal. An important task in blindness prevention of Jiangsu province still is the elimination of cataract blindness and the improvement of visual outcomes for cataract surgery in the future.

[Expression of PTEN, matrix metaloproteinases 2 and 9 in thymomas].

OBJECTIVE: To evaluate the expression of PTEN, MMP-2 and MMP-9 in thymomas and their correlation with clinical significance. METHODS: Immunohistochemical S-P assay was used to detect the expression of PTEN, MMP-2 and MMP-9 in 45 thymomas and 16 non-neoplastic thymuses. RESULTS: The positive rate of PTEN, MMP-2 and MMP-9 expression in 45 thymomas were 53.5%, 48.9% and 62.2%, respectively. There were significant differences between non-neoplastic thymus and thymomas (P < 0.05). The expression of PTEN, MMP-2 correlated with histological type (P < 0.05) and different clinical stage of the thymoma (P < 0.01). The expression of MMP-9 was not correlated with histological type and different clinical stages of thymoma (P > 0.05). CONCLUSION: PTEN, MMP-2 and MMP-9 may play an important role in the occurrence and development of thymoma. The expression of PTEN and MMP-2 correlates with the malignance and the aggression of thymoma.