[Feasibility of a single-port thoracoscopy-assisted five-step laparoscopic procedure via transabdominal diaphragmatic approach for No.111 lymphadenectomy in patients with Siewert type II esophageal gastric junction adenocarcinoma].

Objective: We aimed to explore the feasibility of a single-port thoracoscopy- assisted five-step laparoscopic procedure via transabdominal diaphragmatic(TD) approach(abbreviated as five-step maneuver) for No.111 lymphadenectomy in patients with Siewert type II esophageal gastric junction adenocarcinoma (AEG). Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) age 18-80 years; (2) diagnosis of Siewert type II AEG; (3) clinical tumor stage cT2-4aNanyM0; (4) meeting indications of the transthoracic single-port assisted laparoscopic five-step procedure incorporating lower mediastinal lymph node dissection via a TD approach; (5) Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1; and (6) American Society of Anesthesiologists classification I, II, or III. The exclusion criteria included previous esophageal or gastric surgery, other cancers within the previous 5 years, pregnancy or lactation, and serious medical conditions. We retrospectively collected and analyzed the clinical data of 17 patients (age [mean ± SD], [63.6±11.9] years; and 12 men) who met the inclusion criteria in the Guangdong Provincial Hospital of Chinese Medicine from January 2022 to September 2022. No.111 lymphadenectomy was performed using five-step maneuver as follows: superior to the diaphragm, starting caudad to the pericardium, along the direction of the cardio-phrenic angle and ending at the upper part of the cardio-phrenic angle, right to the right pleura and left to the fibrous pericardium , completely exposing the cardio-phrenic angle. The primary outcome includes the numbers of harvested and of positive No.111 lymph nodes. Results: Seventeen patients (3 proximal gastrectomy and 14 total gastrectomy) had undergone the five-step maneuver including lower mediastinal lymphadenectomy without conversion to laparotomy or thoracotomy and all had achieved R0 resection with no perioperative deaths. The total operative time was (268.2±32.9) minutes, and the lower mediastinal lymph node dissection time was (34.0±6.0) minutes. The median estimated blood loss was 50 (20-350) ml. A median of 7 (2-17) mediastinal lymph nodes and 2(0-6) No. 111 lymph nodes were harvested. No. 111 lymph node metastasis was identified in 1 patient. The time to first flatus occurred 3 (2-4) days postoperatively and thoracic drainage was used for 7 (4-15) days. The median postoperative hospital stay was 9 (6-16) days. One patient had a chylous fistula that resolved with conservative treatment. No serious complications occurred in any patient. Conclusion: The single-port thoracoscopy-assisted five-step laparoscopic procedure via a TD approach can facilitate No. 111 lymphadenectomy with few complications.

Infection Characteristics and Physical Prevention Strategy of Panax notoginseng Round Spot Disease Caused by Mycocentrospora acerina.

Panax notoginseng round spot disease (PRSD), caused by Mycocentrospora acerina, is the main leaf disease occurring in cultured P. notoginseng. Aiming to find a safe and efficient control method for PRSD, we studied the disease characteristics of PRSD and the optimal growth conditions of M. acerina and evaluated the efficacy of rain-shelter cultivation in PRSD control. Moreover, we described M. acerina based on morphological characterization and molecular analyses (ITS, ACT, LSU, and TEF-1α). The optimum temperature for M. acerina conidial germination was found to be 14 to 22°C. Furthermore, leaf surface wetness for at least 4 h is required for conidial germination, and conidia can successfully infect P. notoginseng when the leaf wetness lasts for more than 8 h. Additionally, rainwater splashing determines the conidial transfection distance, which is less than 2 m. Finally, our study revealed that rain-shelter cultivation is an effective and simple physical prevention strategy to control PRSD, with an average efficacy of up to 100%.

[Efficacy observation of the caudal-medial approach combined with "page-turning" middle lymphadenectomy in the laparoscopic right hemicolectomy].

Objective: To investigate the safety and feasibility of caudal-medial approach combined with "page-turning" middle lymphadenectomy in the laparoscopic right hemicolectomy. Methods: A descriptive cohort study was conducted. Clinical data of 35 patients who underwent laparoscopic radical right hemicolectomy using caudal-medial approach combined with "page-turning" middle lymphadenectomy at Department of Gastrointestinal Surgery, Guangdong Hospital of Chinese Medicine from April 2018 to May 2020 were retrospectively analyzed. All operations were performed consecutively by the same surgeon. The caudal-medial approach was used to dissect the right Toldt's fascia and the anterior pancreaticoduodenal space in a caudal-to-cranial and medial-to-lateral manner guided by the duodenum. The "page-turning" middle lymphadenectomy was used to dissect the mesocolon along the superior mesenteric vein with ileocolic vein, Henle's trunk and pancreas exposed preferentially. Results: All the 35 patients completed the operation successfully, and there was no damage and bleeding of superior mesenteric vessels and their branches. The operative time was (186.9±46.2) minutes, and the blood loss was 50 (10-200) ml. The first time to flatus was (2.1±0.6) days, and the time to fluid intake was (2.5±0.8) days. The postoperative hospital stay was 6 (3-18) d. The overall morbidity of postoperative complication was 8.6% (3/35), including grade II in 1 cases (2.8%) and grade IIIa in 2 case (5.7%) according to the Clavien-Dindo grading standard. The total number of lymph node dissected was 30.2±5.6, and the positive lymph node was 0 (0-7). Tumor staging revealed 5 cases of stage I, 18 cases of stage II, 11 cases of stage III, and 1 case of stage IVA. In this study, the median follow-up time was 15 (4-29) months. One patient died due to cerebrovascular accident 12 months after surgery, and no tumor recurrence or metastasis was observed in all other patients. Conclusions: Laparoscopic radical right hemicolectomy using caudal-medial approach combined with "page-turning" middle lymphadenectomy is safe and feasible. The anterior pancreaticoduodenal space is preferentially mobilized, which reduces the difficulty of central vascular dissection.

Application of simulated puncture in percutaneous nephrolithotomy.

OBJECTIVE: This study aimed to explore the clinical value of simulated puncture in percutaneous nephrolithotomy in the treatment of complex kidney stones. PATIENTS AND METHODS: A total of 120 patients with complex kidney stones who were treated with percutaneous nephrolithotomy in our hospital between March 2017 and March 2020 were enrolled in this study and randomly divided into two groups: the research group and the control group (n = 60 in each). Each subject underwent a dual-source computed tomography (CT) scan of the pelvis and both kidneys before the operation. The research team imported the CT data into Mimics19 software to create a three-dimensional (3D) reconstruction of the skin, bones, kidneys, collecting system, and stones. Based on the 3D reconstruction model, the target renal calyx to be punctured was determined, the best puncture channel was designed, and puncture was simulated. Data regarding the simulated puncture were imported into 3-Matics11 software; the angle and depth of the puncture were measured, and then these data were used to guide percutaneous nephrolithotomy. 3D reconstruction and simulated puncture were not undertaken for the patients in the control group before the operation. The effects of treatment in the two groups were compared. RESULTS: First-stage percutaneous nephrolithotomy was successfully completed in both groups of patients. The outcome was better in the research group than in the control group in terms of operation time, number of punctures required for successful establishment of a percutaneous renal channel, number of percutaneous kidney puncture channels, and intraoperative blood loss, and the differences were statistically significant (p < 0.05 for all). The stone clearance rate was higher in the research group than in the control group, but the difference was not statistically significant (p = 0.471). The incidence of penetrating kidney injury was lower in the research group than in the control group, but the difference was not statistically significant (p = 0.154). CONCLUSIONS: For patients due to undergo percutaneous nephrolithotomy for the treatment of complex kidney stones, preoperative simulated puncture helps to improve the puncture accuracy and to reduce the number of punctures required for successful establishment of a percutaneous renal channel, the number of puncture channels, the operation time, and the blood loss, and therefore it is worth promoting.

[Safety and feasibility of laparoscopic double-flap technique in digestive tract reconstruction after proximal gastrectomy for esophagogastric junction tumors larger than 5 cm].

Objective: To investigate the safety and feasibility of laparoscopic double-flap technique (Kamikawa) in digestive tract reconstruction after proximal gastrectomy for esophagogastric junction (EGJ) leiomyoma and gastrointestinal stromal tumor (GIST) with the maximum diameter >5 cm. Methods: A descriptive case-series study was used to retrospectively analyze the data of patients with EGJ leiomyoma and GIST undergoing laparoscopic-assisted proximal gastrectomy and double-flap technique (Kamikawa) at the Department of Gastrointestinal Surgery, Guangdong Hospital of Traditional Chinese Medicine from September 2017 to March 2019. All the tumors invaded the cardia dentate line, and the maximum diameter was >5 cm. After the exclusion of patients requiring emergency surgery and complicating with severe cardiopulmonary diseases, a total of 4 patients, including 3 males and 1 female with age of 29-49 years, were included in this study. After laparoscopic-assisted proximal gastrectomy, the residual stomach was pulled out of the abdominal cavity and marked with methylene blue at the proximal end 3~4 cm from the anterior wall of the residual stomach in the shape of "H". The gastric wall plasma muscular layer was cut along the "H" shape, and the space between the submucosa and the muscular layer was separated to both sides along the longitudinal incision line to make the seromuscular flap. The residual stomach was put back into the abdominal cavity. Under laparoscopy, 4 stitches were intermittently sutured at the upside of "H" shape and 4-5 cm from the posterior wall of the esophageal stump. The stump of the esophagus was cut open, and the submucosa and mucosa were cut under the "H" shape to enter the gastric cavity. The posterior wall of the esophageal stump was sutured continuously with the gastric stump mucosa and submucosa under laparoscopy. The anterior wall of the esophageal stump was sutured continuously with the whole layer of the residual stomach. The anterior wall of the stomach was sutured to cover the esophagus. The anterior gastric muscle flap was sutured and embedded in the esophagus to complete the reconstruction of digestive tract. The morbidity of intraoperative complications and postoperative reflux esophagitis and anastomosis-related complications were observed. Results: All the 4 patients completed the operation successfully, and there was no conversion to laparotomy. The median operative time was 239 (192-261) minutes, the median Kamikawa anastomosis time was 149 (102-163) minutes, and the median intraoperative blood loss was 35 (20-200) ml. The abdominal drainage tube and gastric tube were removed, and the fluid diet was resumed on the first day after surgery in all the 4 patients. The median postoperative hospitalization time was 6 (6-8) days. Postoperative pathology revealed 3 leiomyomas and 1 GIST. There were no postoperative complications such as anastomotic leakage or stenosis, and no reflux symptoms were observed. The median follow-up time was 22 (11-29) months after the operation, and no reflux esophagitis occurred in any of the 4 patients by gastroscopy. Conclusion: For >5 cm EGJ leiomyoma or GIST, double-flap technique (Kamikawa) used for digestive tract reconstruction after proximal gastrectomy is safe and feasible.

[Comparison of the accuracy of predicting prognosis of brain function in patients after cardiopulmonary cerebral resuscitation with two kinds of electroencephalogram techniques combined with neuron-specific enolase].

Objective: To compare the accuracy of electroencephalography (EEG) grading or amplitude-integrated electroencephalography (aEEG) grading combined with NSE in predicting brain function prognosis after cardiopulmonary cerebral resuscitation (CPR) in adults. Methods: The patients who were admitted to Fujian Medical University Union Hospital after CPR from January 2015 to June 2019 were enrolled. Demographic data, Glasgow coma scale (GCS), blood neuron specific enolase (NSE), EEG grading and aEEG grading were collected. The main clinical outcome was the prognosis of brain function (Glasgow-Pittsburgh cerebral performance category, CPC) in patients at 3 months after CPR. Accordingly, the patients were divided into two groups: favorable prognosis group and poor prognosis group, and relevant parameters were compared between the two groups. The predictive ability of EEG grading or aEEG grading combined with NSE for brain function prognosis was evaluated by receiver operating characteristic (ROC) curve. Results: A total of 57 patients were enrolled, with 34 males and 23 females. The average age was (65±19) years old. In terms of Young EEG scales, there was 16 grade 1 cases (28.1%), 24 grade 2-5 cases (42.1%) and 17 grade 6 cases (29.8%), respectively. As for aEEG grading, there was 11 grade Ⅰ cases (19.3%), 25 grade Ⅱ cases (43.9%) and 21 grade Ⅲ cases (36.8%), respectively. There was no significant difference of age, sex, length of stay between the two groups (all P>0.05). However, there was significant difference of EEG grading scale, aEEG grading, GCS grading and NSE between the two groups (all P<0.05). The area under curve (AUC) of NSE, EEG grading and aEEG grading for predicting brain function prognosis was 0.81, 0.82 and 0.85, respectively (all P<0.01). In aEEG grading combined with NSE group, the AUC of was 0.92, and the optimal cut-off point was 4.5, with a sensitivity of 95.8% and a specificity of 79.0%. In EEG grading combined with NSE group, the AUC was 0.90, and the optimal cut-off point was 3.6, with a sensitivity of 92.1% and a specificity of 77.0%. Conclusions: aEEG grading combined with NSE is more accurate in predicting prognosis in patients with cardiopulmonary cerebral resuscitation when compared to EEG grading. Considering its feasibility, aEEG grading combined with NSE is more suitable for clinical application.

[Effects of parental rearing patterns and their consistency on the emotional and behavioral problems of preschool children].

Objective: To explore the effect of parental rearing patterns and their consistency on the emotional and behavioral problems of preschool children. Methods: From October to November 2017, 27 987 children aged 3 to 6 years old from 109 kindergartens in 11 cities of Hubei, Anhui and Jiangsu Provinces were selected by using the cluster sampling method. A total of 27 200 valid questionnaires which were completed by subjects' parents were collected. The emotional and behavioral problems of preschool children were collected by "strengths and difficulties questionnaire" and the parental rearing patterns were evaluated by the "Parental Behavior Scale". The differences in emotional and behavioral abnormality rates of preschool children with different characteristics were analyzed; with emotional and behavioral problems as dependent variables and parental support/participation and compulsion/hostility as independent variables, the multivariate logistic regression model was used to analyze the effect of parental rearing patterns and their consistency on the emotional and behavioral problems of preschool children. Results: The age of children was (4.35±0.96) years old, and 51.4% of children were 13 975 males. There were 24 634 (90.6%) urban children and 17 916 (65.9%) only children. Both parents with strong support/participation accounted for 14.9%, and those with poor support/participation accounted for 11.9%; both parents with strong compulsion/hostility accounted for 15.2%, and those with low compulsion/hostility accounted for 11.3%. The rates of emotional symptoms, conduct behavior, hyperactive behavior, peer interaction, total difficulty score, and abnormal prosocial behavior of preschool children were 9.5%, 9.5%, 18.2%, 24.5%, 11.2%, and 10.2%, respectively. The multivariate logistic regression model analysis showed that after adjusting for gender, only child, living area, family economic status, mother's age and education level, father's education level, and other factors, compared with fathers/mothers with strong support/participation and low compulsion/hostility and parents with strong support/participation and low compulsion/hostility, preschool children who had fathers/mothers with poor support/participation and strong compulsion/hostility or parents with poor support/participation and strong compulsion/hostility were more likely to have emotional symptoms, conduct behavior, hyperactive behavior, peer interaction, total difficulty score, and abnormal prosocial behavior (P<0.05). Conclusions: Parental rearing patterns and their consistency are related to the emotional and behavioral problems of preschool children.

Inhibition of cyclooxygenase-2-mediated matriptase activation contributes to the suppression of prostate cancer cell motility and metastasis.

Chronic inflammation plays an important role in cancer development and progression. Cyclooxygenases-2 (COX-2) is a key enzyme in generating prostaglandins causing inflammation, is often found to be overexpressed in prostate cancer (PCa) and is correlated with PCa cell invasion and metastasis. We aim to investigate the molecular mechanism of how COX-2 promotes PCa cell invasion and metastasis and to evaluate the effect of COX-2 inhibitors in a selected model of PCa progression. Our results showed that the expression of COX-2 and Interleukin 1ß (IL-1ß) was upregulated in highly invasive PCa cells and was correlated with the activated levels of membrane-anchored serine protease matriptase. The expression levels of COX-2 were increased and were correlated with matriptase levels in PCa specimens. Moreover, results showed that COX-2 overexpression or a COX-2 product Prostaglandin E2 (PGE2) caused an increase in matriptase activation and PCa cell invasion, whereas COX-2 silencing antagonized matriptase activation and cell invasion. In addition, the inhibition of COX-2-mediated matriptase activation by Celebrex and sulindac sulfide suppressed the androgen-independent and COX2-overexpressing PCa PC-3 cell invasion, tumor growth and lung metastasis in an orthotopic xenograft model. Our results indicate that COX-2/matriptase signaling contributes to the invasion, tumor growth and metastasis of COX-2-overexpressing and androgen-independent PCa cells.

Effects of a structured exercise programme in sedentary dogs with chronic diarrhoea.

The aim of this investigation was to evaluate the effects of a structured exercise programme in sedentary dogs with chronic diarrhoea. Twenty-two dogs were enrolled in the study. All dogs received oral prednisolone (1 mg/kg/day for 14 days, followed by a tapering dosage) for 10 weeks. After four weeks of prednisolone treatment, dogs were assigned to either the exercise or control group (n=11 each). Owners of dogs in the exercise group were instructed to guide their dogs in structured exercise training (low-intensity to moderate-intensity aerobic and resistance exercise three to five days per week). After 10 weeks of prednisolone treatment with concomitant 6 weeks of complementary exercise, the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) score had decreased significantly in the exercise group (from 8.8±1.5 at the start of the exercise programme to 2.4±1.5; P<0.001); no such change was observed in the control group (from 9.2±0.9 to 9.2±1.1). CIBDAI scores differed significantly between the groups at the end of the 10-week study period (P<0.001). The exercise programme affected all six CIBDAI parameters significantly; bodyweight (P<0.001, adjusted r2=0.722) was most affected. A structured exercise programme may have positive effects on clinical symptoms in sedentary dogs with chronic diarrhoea.

[Effects of chronic intermittent hypoxia on hepatic function and protective mechanism of adiponectin in rats].

Objective: To explore the effect of chronic intermittent hypoxia (CIH) on rats hepatic function, and the protective mechanism of adiponectin (Ad). Methods: Sixty healthy male wistar rats were randomly divided into 4 groups: normal control (NC), NC+ Ad, CIH, and CIH+ Ad groups with 15 rats in each. The rats in CIH and CIH+ Ad groups were exposed to an intermittent hypoxic chamber 8 hours per day for 4 months. Meanwhile, the rats in both the NC and NC + Ad groups were housed with normal pressure air. The rats in the NC+ Ad and CIH+ Ad groups were additionally treated with an intravenous injection of Ad (10 µg), twice a week for 4 months. At the end of experiment, comparison among groups was made about plasma levels of aspartate amino transferase (AST), alanine amino transferase (ALT), degrees of endoplasmic reticulum stress (ERS) and mitochondrium associated cellular apoptosis. Results: No significant difference was detected in all items between NC and NC+ Ad groups (all P>0.05). Plasma hepatic enzyme levels of AST and ALT were significantly higher in CIH group [(319±21) and (113±9) U/L] than those in NC group [(178±19) and (51±9) U/L] and NC+ Ad group [(175±16) and (52±8) U/L] (all P<0.05). Compared NC with NC+ Ad group, there was more remarkable ERS and mitochondrial injury associated cellular apoptosis in hepatic tissues of CIH group. Such pathological changes were less obvious in CIH+ Ad group than in CIH group (all P<0.05). Conclusion: CIH can induce hepatic injury in rats, while Ad supplement may play a protective role possibly through inhibition of ERS and associated pathways of cellular apoptosis.

The influence of HOXA5-specific siRNA on the expression of Livin and Smac proteins.

OBJECTIVE: To Knockdown Homeobox A5 (HOXA5) expression by HOXA5-specific siRNA and evaluate the effects on Livin and Smac proteins expression in acute T cell leukemia Jurkat cells. MATERIALS AND METHODS: We designed and constructed HOXA5-specific siRNA, and using liposomes we transfected Jurkat cells with this siRNA. The experiment was designed for three groups: (i) experimental group with Jurkat cells transfected with HOXA5-specific siRNA (siRNA transfection group), (ii) negative control group (irrelevant siRNA transfection) with Jurkat cells transfected with pRNAT-U6.1-siD and (iii) normal control group (untransfected Jurkat cells, only with equivalent amounts of cells and medium). We used FQ-PCR and Western blot to detect the relative expression levels of HOXA5 mRNA and protein in each group separately. The Western blot was also used to detect Livin and Smac protein levels in Jurkat cells. RESULTS: Expression levels of HOXA5 mRNA and protein were significantly reduced in the group with Jurkat cells transfected with HOXA5 siRNA (p<0.05). The expression of Livin protein was significantly down-regulated (p<0.05) while the expression of Smac protein was significantly up-regulated (p <0.05). CONCLUSIONS: HOXA5-specific siRNA effectively silenced the HOXA5 gene expression and down-regulation of HOXA5 induced the down-regulation of Livin protein expression and up-regulation of Smac protein. We suggest the HOXA5 gene to be considered as the new target for acute leukemia gene therapy.

[On the epidemic of cholera and its prevention and control by the railway authorities in 1932].

In 1932, the epidemic of cholera in China was serious, spreading to all provinces nationwide, causing heavy casualties. In order to prevent cholera epidemics spread along the railway line, the National Government Ministry of Railways and the local railway administration had taken all countermeasures, including the promulgation of epidemic prevention laws and regulations, quarantine, isolated check-up, disinfection, vaccination and even interruption of traffic. The measures of railway authorities had achieved a certain success. In August 1932, cholera epidemic began to subside gradually.

[Disaster and reconstruction of Chinese Railways Health Career during 1937-1949].

China railways medical career expereniced serious disaster because of Japanese aggressors destorying in Anti-Japanse time. Longhai, zhegan and Xianggui Railways Bureaus carried out the ongoing struggle in the front and rear of War.After the war, state railways health career had began to recover and rebuild, General Hospital as the core of the health administration system and the main railway hospitals had been rebuilt in each railways ministry in 1949, and these were a certain degree of development, but still a gap compared with pre-war.

Cigarette smoke induces mucin hypersecretion and inflammatory response through the p66shc adaptor protein-mediated mechanism in human bronchial epithelial cells.

The p66Shc adaptor protein is a newly recognized mediator of mitochondrial dysfunction and might play a role in cigarette smoke (CS)-induced airway epithelial cell injury. CS can induce an excessive amount of reactive oxygen species (ROS) generation, which can cause mitochondrial depolarization and injury through the oxidative stress-mediated Serine36 phosphorylation of p66Shc. The excessive production of ROS can trigger an inflammatory response and mucin hypersecretion by enhancing the transcriptional activity of pro-inflammatory cytokines and mucin genes. Therefore, we speculate that p66Shc plays an essential role in airway epithelial cell injury and the process of mucin generation in CS-induced chronic inflammatory airway diseases. Our present study focuses on the role of p66Shc in ROS generation, and on the resulting mitochondrial dysfunction, inflammatory response and mucus hypersecretion in CS-stimulated human bronchial epithelial cells (16HBE). We found that CS disturbed the mitochondrial function by increasing the level of phosphorylated p66Shc in these cells and that the effects were significantly reduced by silencing p66Shc. Conversely, the ectopic overexpression of wild-type p66Shc enhanced these effects. We also found that high levels of ROS inhibited FOXO3a transcriptional activity, which led to NF-κB activation. Subsequently, activated NF-κB promoted pro-inflammatory cytokine production and mucin hypersecretion. Thus, manipulating p66Shc might offer a new therapeutic modality with which to treat chronic inflammatory airway diseases.

HAI-2 suppresses the invasive growth and metastasis of prostate cancer through regulation of matriptase.

Dysregulation of cell surface proteolysis has been strongly implicated in tumorigenicity and metastasis. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) in prostate cancer (PCa) cell migration, invasion, tumorigenicity and metastasis using a human PCa progression model (103E, N1, and N2 cells) and xenograft models. N1 and N2 cells were established through serial intraprostatic propagation of 103E human PCa cells and isolation of the metastatic cells from nearby lymph nodes. The invasion capability of these cells was revealed to gradually increase throughout the serial isolations (103E

Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents.

BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) is a chronic inflammatory disease. Histone deacetylase inhibitors (HDACi), a new class of anti-cancer agents, have recently been reported to exhibit potent anti-inflammatory activities. A proof of concept study was carried out with suberoylanilide hydroxamic acid (SAHA) and MS-275, two HDACi currently undergoing clinical investigations for various oncological indications. EXPERIMENTAL APPROACH: The anti-rheumatic effects of SAHA and MS-275 were assessed in both mouse and rat collagen induced arthritis (CIA) models. KEY RESULTS: SAHA exhibited moderate prophylactic efficacy. It attenuated paw swelling due to inflammation, decreased bone erosion in both mice and rats and reduced slightly the RA-induced bone resorption in rats. However, SAHA could not inhibit the onset of arthritis. In contrast, MS-275 displayed dramatic anti-rheumatic activities. In prophylactic intervention, high doses of MS-275 prevented bone erosion and markedly delayed the onset of arthritis; at low doses, MS-275 strongly attenuated paw swelling, bone erosion, and bone resorption associated with RA. Furthermore, the therapeutic efficacy of MS-275 was also documented. After the onset of arthritis, it could stop the disease progression and joint destruction. An anti inflammatory effect of MS-275 was also confirmed through its capacity to decrease serum IL-6 and IL-1beta levels in the CIA induced mouse model. The anti-rheumatic activity of MS-275 was also confirmed through histological observation. No synovial hyperplasia, pannus formation, cartilage or bone destruction were observed in the high dose prophylactic intervention in mice. CONCLUSION AND IMPLICATION: This study strongly supported HDACi as an innovative therapeutic strategy for RA.

Long latency of evoked quantal transmitter release from somata of locus coeruleus neurons in rat pontine slices.

The locus coeruleus (LC) harbors a compact group of noradrenergic cell bodies projecting to virtually all parts of the central nervous system. By using combined measurements of amperometry and patch-clamp, quantal vesicle release of noradrenaline (NA) was detected as amperometric spikes, after depolarization of the LC neurons. After a pulse depolarization, the average latency of amperometric spikes was 1,870 ms, whereas the latency of glutamate-mediated excitatory postsynaptic currents was 1.6 ms. A substantial fraction of the depolarization-induced amperometric spikes originated from the somata. In contrast to glutamate-mediated excitatory postsynaptic currents, NA secretion was strongly modulated by the action potential frequency (0.5-50 Hz). Somatodendritic NA release from LC upon enhanced cell activity produced autoinhibition of firing and of NA release. We conclude that, in contrast to classic synaptic transmission, quantal NA release from LC somata is characterized by a number of distinct properties, including long latency and high sensitivity to action potential frequency.

Chemotherapy for ovarian mucinous cystadenocarcinoma during pregnancy: a case report.

There is limited experience in the treatment of epithelial ovarian malignancy with chemotherapy during pregnancy. We present the case of a 36-year-old women with ovarian mucinous cystadenocarcinoma during pregnancy, on whom exploratory laparotomy was performed at the gestational age of 16 weeks. Afterwards chemotherapy with cyclophosphamide (500 mg/m2) and cisplatin (50 mg/m2) was administered beginning at the second trimester of pregnancy due to surgical Stage Ic. Although preterm labor and a prematurely ruptured membrane occurred at the gestational age of 29 weeks before the fourth course of chemotherapy, there was still a satisfactory outcome for mother and fetus after an emergency cesarean section due to breech presentation at the gestational age of 30 weeks.