[Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases].

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

[Quality control of gastric resection range in laparoscopic locally advanced gastric cancer].

After nearly 30 years of exploration and practice, minimally invasive surgical techniques represented by laparoscopic technology have become an important means for the surgical treatment of gastric cancer. In China, laparoscopic radical resection for locally advanced gastric cancer has been extensively carried out. However, there are still controversies regarding the gastric resection range and methods for advanced gastric cancer. By reviewing relevant domestic and foreign guideline documents and combining team practice experience, this article elaborates on the key points of quality control of laparoscopic gastric resection range for locally advanced gastric cancer from aspects such as tumor localization and gastric resection range for upper, middle and lower gastric tumors. It aims to provide reference for carrying out and promoting laparoscopic radical gastrectomy more safely.

[Technical difficulties and countermeasures of digestive tract reconstruction in robotic radical gastrectomy for gastric cancer].

There still remain some problemsin digestive tract reconstruction after robotic radical gastrectomy for gastric cancer at present, such as great surgical difficulties and high technical requirements. Based on the surgical experience of the Gastric Surgery Department of Union Hospital, Fujian Medical University and the literatures at home and abroad, relevant issues are discussed in terms of robotic radical distal gastrectomy (Billroth I, Billroth II, and Roux-en-Y gastrojejunostomy), proximal gastrectomy (double-channel and double-muscle flap anastomosis), and total gastrectomy (Roux-en-Y anastomosis, functional end-to-end anastomosis, FEEA, π-anastomosis, Overlap anastomosis, and modified Overlap anastomosis with delayed amputation of jejunum, i.e. later-cut Overlap). This article mainly includes (1) The principles of digestive tract reconstruction after robotic radical gastrectomy for gastric cancer. (2) Digestive tract reconstruction after robotic radical distal gastrectomy: Aiming at the weakness of traditional triangular anastomosis, we introduce the improvement of the technical difficulty, namely "modified triangular anastomosis", and point out that because Billroth II anastomosis is a common anastomosis method in China at present, manual suture under robot is more convenient and safe, and can effectively avoid anastomotic stenosis. (3) Digestive tract reconstruction after robotic proximal gastrectomy: It mainly includes double channel anastomosis and double muscle flap anastomosis, but these reconstruction methods are relatively complicated, and robotic surgery has not been widely carried out at present. (4) Digestive tract reconstruction after robotic total gastrectomy: The most classic one is Roux-en-Y anastomosis, mainly using circular stapler for end-to-side esophagojejunal anastomosis and linear stapler for side-to-side esophagojejunal anastomosis, for which we discuss the solutions to the existing technical difficulties. With the continuous innovation of robotic surgical system and anastomosis instruments, and with the gradual improvement of anastomosis technology, it is believed that digestive tract reconstruction after robotic radical gastrectomy for gastric cancer will have a good application prospect in gastric cancer surgery.

[The mechanisms of the translation of polymerase from HBV pregenomic RNA].

Hepatitis B virus (HBV) is an important pathogen that causes different liver diseases such as viral hepatitis and liver cirrhosis. HBV pregenomic RNA (pgRNA) plays a crucial role in HBV life cycle, which is not only the translation template of core (C) and polymerase (P), but also the template of reverse transcription. The ratio of P protein to core protein is tightly regulated. Since P and core are both translated by pgRNA and the open reading frame (ORF) of P is located downstream of the ORF of core, how to initiate P protein translation is a key scientific question. Previous studies suggest that P can be translated through different mechanisms, such as leaky scanning and reinitiation. In this review, we summarized the proposed mechanisms relevant to the translation of polymerase from HBV pgRNA through literature review and derivation.

[Studies on efficacy of a bioabsorbable steroid-eluting sinus stent in the frontal sinus opening of chronic rhinosinusitis with nasal polyps].

Objective: To assess the efficacy of a bioabsorbable steroid-eluting sinus stent in improving surgical outcomes when placed in the frontal sinus ostium (FSO) following full endoscopic sinus surgery (ESS) in patients with whole group chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients with whole group CRSwNP who had similar lesions on bilateral sinus between September 2019 and March 2020 in Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Changhai Hospital were chosen. Patients with CRSwNP who underwent extended ESS were randomly assigned to receive a steroid-eluting sinus stent in one FSO whereas the contralateral side received surgery alone. Endoscopic evaluations recorded at 30, 90 days postoperative were graded by an independent assessment panel to assess the need for interventions in the FSO. Semi-quantitative data with CT and endoscopic score were performed by rank sum test. The need for postoperative intervention and the patency rate of FSO were analyzed using the McNemar test. Results: Thirty-one patients with whole group CRSwNP met all eligible criteria, including 17 males and 14 females, with the age of (44.5±11.8) years(x¯±s). Stents were successfully placed in one FSO of all patients. At 30 days post-ESS, the assessment panel reported that steroid-eluting stents reduced the need for postoperative interventions by 41.0% (χ2=5.314,P=0.021), the need for oral steroid interventions by 40.0% (χ2=4.133,P=0.042) and the need for surgical interventions by 74.8% (χ2=4.292,P=0.038) compared to control sinuses with no stents. Clinical surgeons also reported greater diameter of FSO compared to control sinuses at 30 days post-ESS (74.2% vs 48.4%, χ2=4.351, P=0.037). These results at 90 days post-ESS were consistent with those at 30 days post-ESS. Conclusion: Bioabsorbable steroid-eluting sinus stents in the FSO can reduce polyp formation, adhesion, and the need for postoperative interventions in FSO of CRSwNP patients and improve the early postoperative outcomes.

Hsa-miR-34a-5p reverses multidrug resistance in gastric cancer cells by targeting the 3'-UTR of SIRT1 and inhibiting its expression.

Multidrug resistance (MDR) is a major obstacle to chemotherapy, which leads to ineffective chemotherapy, an important treatment strategy for gastric cancer (GC). The abnormality of microRNAs (miRNAs) is critical to the occurrence and progression of MDR in various tumors. In this study, hsa-miR-34a-5p was found to be decreased in multidrug resistant GC cells SGC-7901/5-Fluorouracil (SGC-7901/5-Fu) compared to the parental SGC-7901 cells. Overexpression of hsa-miR-34a-5p in SGC-7901/5-Fu cells promoted apoptosis and decreased migration and invasiveness after chemotherapy. In addition, overexpression of hsa-miR-34a-5p suppressed the growth of drug-resistant tumor in vivo. The mechanism of the effects of hsa-miR-34a-5p could include the regulation of the expression of Sirtuin 1 (SIRT1), P-glycoprotein (P-gp) or Multidrug resistance-related protein 1 (MRP1) through direct binding to the 3'-untranslated region (UTR) of SIRT1. Functional gain-and-loss experiments indicated that hsa-miR-34a-5p enhances the chemotherapy sensitivity of MDR GC cells by inhibiting SIRT1, P-gp and MRP1. In conclusion, hsa-miR-34a-5p can reverse the MDR of GC cells by inhibiting the expression of SIRT1, P-gp or MRP1.

[Clinical analysis of selective laryngeal reinnervation using upper root of phrenic nerve and hypoglossal nerve branch in the treatment of bilateral vocal fold paralysis].

Objective: To evaluate the airway and voice quality improvement in patients with bilateral vocal fold paralysis (BVFP) who underwent selective laryngeal reinnervation surgery. Methods: From January 2012 to December 2016, a retrospective study was conducted in 39 patients with BVFP who underwent selective laryngeal reinnervation surgery in Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Navy Medical University. All patients were examined by videostroboscopy, vocal function assessment, laryngeal electromyography and pulmonary function test before and after the surgery, and followed up for at least 2 years to evaluate the efficacy and safety of the surgery.Wilcoxon signed rank test was used to analyze the G score and VHI-10 score data. Paired t-test was used to analyze acoustic parameters, MPT values and pulmonary function parameters. Results: Postoperative infection and hemorrhage occurred in one patient separately.Videostroboscopic videos showed that at 4-8 months postoperatively, vocal folds in 35 patients achieved moderate or severe abduction during inspiration, 2 patients only achieved mild abduction, 2 patients showed no abduction,while all patients achieved adduction in bilateral vocal cords during phonation. The recovery rate of moderate-to-severe abduction was 89.7% (35/39), and these patients were decannulated successfully. At 12 months after operation, G score and VHI-10 score were significantly lower than those before operation (P<0.05), and the acoustic parameters jitter, shimmer, HNR and MPT were significantly improved (P<0.05). Most of the parameters of the pulmonary function test at 3 months postoperatively returned to the normal reference level, while the maximum inspiratory pressure (PImax) at 12 months after operation was still slightly lower than the normal level, but it was significantly improved compared with preoperative value (P<0.05). The EMG data at 12 months postoperatively showed full interference potentials in 37 patients in bilateral posterior cricoarytenoid muscles during inspiration, and full interference potentials in bilateralthyroarytenoid muscles during phonation. Obvious misdirected regeneration electric activitieswere found in two of them. Potentials in posterior cricoarytenoid muscle were weak in 2 cases with poor abduction. During long-term follow-up, only one case showed decreased abduction, but did not affect respiratory function. Conclusions: The selective laryngeal reinnervation procedure applied in the present study can restore physiological motion of vocal cords. The success rate was high, the curative effect was stable, and the complications were rare. It is worth of promotion.

[The surgical effectiveness of montgomery thyroplasty implant on patients with unilateral vocal fold paralysis].

Objective: To investigate the efficacy of type I thyroplasty with Montgomery prosthesis implantation for the treatment of unilateral vocal fold paralysis. Methods: From May 2015 to March 2019, 46 patients (24 males, 22 females, with age range of 23-77) with unilateral vocal fold paralysis underwent thyroplasty with Montgomery prosthesis implantation in the Department of Otorhinolaryngology Head and Neck Surgery in both the First Affiliated Hospital of Navy Medical University and Guangdong Provincial People's Hospital. The assessment methods included GRBAS auditory perception assessment, acoustic analysis such as Jitter, Shimmer, NHR and maximum phonation time (MPT). Results: Postoperative videostroboscopy observed the displacement of paralyzed vocal fold to the midline in 44 cases as well as significantly reduced glottic fissures during phonation. In the other 2 cases, glottic fissure did not reduce significantly. Compared with preoperative data, the scores of all parameters in GRBAS auditory perception assessment were lower except the parameter S, and the acoustic analysis parameters (jitter, shimmer, NHR) were smaller, and MPT was longer. All the difference was statistically significant (P<0.001). Revision surgery was performed in 2 patients with poor results. No serious complications occurred in all the cases. Conclusions: For the patients with unilateral vocal fold paralysis who are not suitable for the laryngeal reinnervation surgery due to old age or long course of denervation, thyroplasty with Montgomery prosthesis implantation can effectively improve the voice of patients with high safety,which is worthy of promotion.

[Correlation analysis of standardized palatal sensory threshold with airway obstruction and hypoxia during sleep].

Objective: To study the correlation between the standardized palatal sensory threshold and airway obstruction and hypoxia during sleep, and to infer its role in the pathogenesis of OSAHS. Methods: From August 2016 to May 2017, 92 OSAHS patients as experimental group and 48 non-OSAHS volunteers as control group were recruited in Department of Otorhinolaryngology Head and Neck Surgery, Changhai Hospital Affiliated to the Naval Medical University. The tactile sense was measured by Smmes-Weinstein Monofilaments in the middle of uvula and both side of hard palate,then the threshold of the uvula minus, the average threshold of the hard palate as the standardized palatal sensory threshold(SPST). The control point of both groups was located in the central underlip. Mann-Whitney U test for comparing two independent samplesand partial correlation analysis. Results: There was no difference in tactile threshold of underlip between the experimental group and the control group(0.020[0.008,0.020] g/mm(2) vs. [0.020(0.008,0.020] g/mm(2), Z=293.0, P=0.221); the tactile sense of the experimental group was larger than that of the control group in thehardpalate(0.040[0.140,0.055] g/mm(2) vs. 0.138[0.064,0.400] g/mm(2), Z=4.5, P=0.000), soft palate(0.400[0.280,0.400] g/mm(2) vs. 1.400[1.000,4.000] g/mm(2), Z=0, P=0.000) and SPST(0.355[0.125,0.373] g/mm(2) vs. 1.285[0.896,3.025] g/mm(2), Z=0, P=0.000). The SPST was positive correlation with apnea hypopneaindex(AHI)(r=0.835, P=0.000) and negative correlation with the nadir oxyhemoglobin saturation (r=-0.636, P=0.000). Conclusion: The greater the standardized palatal sensory threshold, the worse the condition of OSAHS, the lower, the lowest blood oxygen at night, and the impaired upper airway sensory function plays an important role in the pathogenesis of OSAHS.

[Optimization of delivering minimum Gd-DTPA at the posterior upper point on tympanic medial wall and hT2W-3D-FLAIR sequence for detecting endolymphatic hydrops].

Objective: To optimize delivery of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA) at the posterior upper point on tympanic medial wall and heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery (hT2W-3D-FLAIR) sequence, and to implement the technique of detecting endolymphatic hydrops using gadolinium-enhancement MRI. Methods: Thirteen patients with periphery vertigo, who visited Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Changhai Hospital during June and December of 2017, were enrolled in the study.0.10-0.20 ml of Gd-DTPA in various dilutions (10, 20, and 40-fold) were delivered at the posterior upper point on tympanic medial wall using a soft-tipped tympanic suction and drug-spraying needle through an artificially perforated tympanic membrane. Inner ear MRI was performed at 8, 24 h after Gd-DTPA administration using a 3T MR machine in combination with a 20-channel Tim 4G head/neck coil and the sequence of hT2W-3D-FLAIR to detect the gadolinium-enhancement signal within the inner ear and possible endolymphatic hydrops. The scanning time was either 8 min 35 s or 15 min 11 s. Results: Efficient inner ear uptake of Gd-DTPA was detected and induced high signal to noise ratio of MRI in patients receiving targeted delivery of 0.15-0.20 ml of 10-fold diluted contrast agent at the posterior upper point on tympanic medial wall. At 8 h after delivery, significant uptake was detected in the scala tympani and vestibuli of hook region and basal turn of the cochlea, and perilymhatic compartment of the vestibule. At 24 h after delivery, the distribution of Gd-DTPA became homogenous in each turn of the cochlea and perilymphatic compartment of the vestibule. However, obvious individual variance existed in the inner ear uptake when 0.10 ml of 40-fold diluted Gd-DTPA was delivered. Efficient inner ear uptake and high quality images that generated in patients receiving 0.10, 0.15, and 0.20 ml of 20-fold Gd-DTPA demonstrated endolymphatic hydrops with minor individual variance. There was insignificant difference in the enhancement signal of inner ear between 0.15 and 0.10 ml groups when Gd-DTPA was diluted at 20-fold except for the signal of semicircular canal of 0.15 ml group (190.00±53.95 vs 165.50±42.13, t=2.61, P<0.05). There was insignificant difference in the image quality between 8 min 35 s and 15 min 11 s canning time. Various degrees of endolymphatic hydrops were detected in 7 cochleae and 11 vestibule, and both simultaneous cochlear and vestibular endolymphatic hydrops were detected in 4 ears. Cochlear endolymphatic hydrops was detected in all the 3 patients with definite Meniere's disease, and 2 of them had combined cochlear and vestibular endolymphatic hydrops. Endolymphatic hydrops was not detected in patients with possible Meniere's disease nor with symptoms of superior semicircular canal dehiscence. Conclusion: Targeted delivery of 0.10 ml with 20-fold diluted Gd-DTPA (total dosage of 5 µmol) at the posterior upper point on tympanic medial wall in combination with 8 min 35 s scanning time hT2W-3D-FLAIR sequence for inner ear MRI in a 3T MR machine is a clinically practical method to detect endolymphatic hydrops, and reduce the requirement for MRI hardware.

[The efficacy of ansa cervicalis anterior root for unilateral recurrent laryngeal nerve injury].

Objective: To discuss the long-term efficacy of laryngeal reinnervation using the anterior root of the ansa cervicalis in the treatment of unilateral vocal fold paralysis (UVFP) caused by thyroid surgery. Method: From January 2010 to January 2016, a total of 39 UVFP patients who underwent ansa cervicalis anterior root-to-recurrent laryngeal nerve (RLN) anastomosis and who had suffered nerve disfunction for 6 to 24 months were enrolled as UVFP group.Another 39 age and gender matched normal subjects served as control group. Videostroboscopy, vocal function assessment (acoustic analysis, perceptual evaluation and maximum phonation time), and laryngeal electromyography were performed preoperatively and postoperatively for assessing surgery efficacy. Paired sample t test was used for statistical analysis. Result: Videostroboscopic reports indicated that the glottic closure, vocal fold edge, vocal fold position, phase symmetry and regularity were significantly improved in the UVFP group (P<0.01, respectively, postoperative vs. preoperative)and showed no statistical differences compared to the control group (P>0.05, respectively). Both the postoperative GRBAS assessment and acoustic parameters were also significantly improved in the UVFP group, Pre-operative acoustic parameters/Post-operative acoustic parameters were 1.68±0.82/0.39±0.27, 10.08±2.56/4.58±2.96, 0.203±0.216/0.018±0.038, 5.96±1.92/17.42±4.11(P<0.01, respectively) and Pre-operative acoustic parameters/Post-operative acoustic parameters were 0.39±0.27/0.32±0.19, 4.58±2.96/3.32±1.27, 0.018±0.038/0.014±0.027, 17.42±4.11/18.76±5.29, which showed no statistical differences compared to the control group (P>0.05, respectively). Conclusion: Delayed laryngeal reinnervation with the anterior root of ansa cervicalis, it can restore the physiological laryngeal phonatory function to the normal or a nearly normal voice quality, which is a feasible and effective approach for the treatment of thyroid surgery-related UVFP.

[The role of NF-κB signaling pathway in laryngeal leukoplakia recurrent with laryngeal reflux].

Objective: To study the mechanism of vocal mucosal barrier damage mediated by NF-κB and NF-κB-regulated signaling pathway via probing the expression of inflammatory factors and essential proteins for node of NF-κB signaling pathway. Methods: The patients suffering from vocal leukoplakia accompanied with larygopharyngeal reflux(LPR) were treated with oral administration of proton pump inhibitor(PPI). Mucosal specimens of vocal cord were collected from all patients before PPI treatment. And the mucosal specimens of vocal cord were collected from the patients with suspected recurrence at 8 weeks after PPI treatment. HE staining was used to observe the histopathological changes of the mucosa. ELISA was utilized to detect the levels of inflammatory factors including tumor necrosis factor(TNF)-α, interleukin(IL)-1 and IL-6. Western blot was used to detect the expression of p-p65, p-IKK and p-IκB. Immunofluorescence method was adopted to detect the entrance of p65 to cell nucleus.Data was analyzed by SPSS 23.0 software. Results: In PPI untreated group, the expressions of IL-1ß, TNF-α and IL-6 in the specimens of 8 weeks after operation were not different significantly from those obtained during operation.But in the PPI-treated group, the expressions were down-regulated.The expression of p-p65 in the middle and high grade heterogenous hyperplasia group was higher than that of low level heterogenous hyperplasia group.The difference of p65 and p-p65 expression between 8 weeks after surgery and surgery in PPI-untreated group was statistically insignificant (P>0.05). The difference of p65 expression between PPI-treated group and PPI pre-treatment group was statistically insignificant (P>0.05). The expression of p-p65 in the PPI-treated group was lower than that of the PPI pre-treatment group (P<0.05). The expressions of IL-1ß, TNF-α and IL-6 were positively related with that of NF-κB-p65. Immun of luorescence method revealed the entrance of p65 to cell nucleus in PPI pre-treatment group, which meant that NF-κB was activated. In the PPI-treated group, few activated p65 could be observed in the cell nucleu. Conclusion: The possible mechanism of vocal mucosal barrier damage in vocal leukoplakia accompanied with LPR maybe the vocal mucosal inflammation mediated by NF-κB and NF-κB-regulated signaling pathway activated with refluxed materials.

[A multicenter randomized controlled study on the treatment of acute and chronic pharyngitis with Binglianqingye Spray].

Objective:To further evaluate the clinical efficacy and safety of Binglianqingye Spray on acute and chronic pharyngitis by clinical observation. Method:A randomized, double-blind and multicenter clinical trial which served Jinsangzi Tablet and Jinhoujian Spray as the control groups was conducted to observe the effect of Binglianqingye Spray on 360 patients with acute and chronic pharyngitis. Result:Binglianqingye Spray could significantly improve the symptoms with the exact clinical efficacy of the acute pharyngitis or chronic pharyngitis, such as sore throat, pharyngeal mucosa and uvula, dry throat burning, headache, cough, pharynx posterior wall lymphoid follicles hyperemia swelling and mandibular angle lymph node swelling and so on, but it occasionally occurred urine abnormalities and urine sugar adverse reactions. At the same time, the taste satisfaction was 82.1%. Conclusion:The combined effects of Binglianqingye Spray on the treatment of acute pharyngitis or chronic pharyngitis are well, the adverse reaction is rare and the patient's compliance is high.

Serotonin induces parathyroid hormone-related protein in goat mammary gland.

During lactation, large amounts of calcium are exported from the mammary gland into milk to ensure skeletal growth of the offspring. Recent studies revealed that serotonin (5-HT) is essential to stimulate skeletal calcium resorption for milk synthesis. Our objective was to explore the correlation between circulating 5-HT and serum calcium and parathyroid hormone-related protein (PTHrP) concentrations around parturition in dairy goats. We also investigated the effect of 5-HT on PTHrP expression in cultured primary goat mammary epithelial cells (GMEC). Blood samples of multiparous Guanzhong dairy goats were collected on day -5 to 3 postpartum for analysis of serum concentrations of calcium, 5-HT, and PTHrP. Results revealed that from day -3 to 0 postpartum serum calcium and 5-HT concentrations decreased progressively, but serum PTHrP concentration only had a sharp drop in the postpartum period sampled. Correlation analysis of circulating 5-HT and serum calcium and PTHrP concentrations on day 1 and 2 postpartum revealed that low serum 5-HT concentration was positively correlated with serum total calcium or PTHrP concentration. By knocking down tryptophan hydroxylase-1 (TPH1) or adding 5-hydroxytryptophan (5-HTP) to decrease or increase the levels of 5-HT in GMEC, we observed that 5-HTP increased PTHrP expression in a dose-dependent manner and siTPH1 decreased PTHrP protein expression. Furthermore, 5-HT increased mRNA abundance of calcium-sensing receptor (CaSR) in a dose-dependent manner and decreased the expression of plasma membrane Ca2+ ATPase-1 (PMCA1). Taken together, 5-HT seems to induce PTHrP expression in goat mammary cells during and after parturition. These findings suggest that increasing 5-HT biosynthesis could be a potential therapeutic target for prevention of hypocalcemia in dairy goats.

Gene deficiency and pharmacological inhibition of caspase-1 confers resilience to chronic social defeat stress via regulating the stability of surface AMPARs.

Both inflammatory processes and glutamatergic systems have been implicated in the pathophysiology of mood-related disorders. However, the role of caspase-1, a classic inflammatory caspase, in behavioral responses to chronic stress remains largely unknown. To address this issue, we examined the effects and underlying mechanisms of caspase-1 on preclinical murine models of depression. We found that loss of caspase-1 expression in Caspase-1-/- knockout mice alleviated chronic stress-induced depression-like behaviors, whereas overexpression of caspase-1 in the hippocampus of wild-type (WT) mice was sufficient to induce depression- and anxiety-like behaviors. Furthermore, chronic stress reduced glutamatergic neurotransmission and decreased surface expression of glutamate receptors in hippocampal pyramidal neurons of WT mice, but not Caspase-1-/- mice. Importantly, pharmacological inhibition of caspase-1-interleukin-1ß (IL-1ß) signaling pathway prevented the depression-like behaviors and the decrease in surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in stressed WT mice. Finally, the effects of chronic stress on both depression- and anxiety-like behaviors can be mimicked by exogenous intracerebroventricular (i.c.v.) administration of IL-1ß in both WT and Caspase-1-/- mice. Taken together, our findings demonstrate that an increase in the caspase-1/IL-1ß axis facilitates AMPAR internalization in the hippocampus, which dysregulates glutamatergic synaptic transmission, eventually resulting in depression-like behaviors. These results may represent an endophenotype for chronic stress-induced depression.