[One case of bromadiolone poisoning leading to intestinal necrosis and severe coagulopathy].

Bromadiolone is still often used in life as a poisonous rodent agent. Bromadiolone poisoning is often manifested as coagulation dysfunction, resulting in organ bleeding, including cerebral hemorrhage, intestinal bleeding, abdominal hemorrhage, etc. At present, no case of intestinal necrosis caused by bromadiolone poisoning have been reported. This article reviewed one case of intestinal necrosis and severe coagulation dysfunction, and finally confirmed bromadiolone poisoning by poison detection. The patient recovered and was discharged after surgery, vitamin K injection, plasma transfusion and other treatment methods.

[Human chorionic gonadotropin-secreting gonadoblastomas in a girl of 45, X Turner syndrome: a case report and literature review].

Objective: To summarize the experience in diagnosis and treatment of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism and bilateral gonadoblastoma (Gb) secreting human chorionic gonadotrophin(HCG). Methods: A female patient aged 5 years and 3 months was admitted to the hospital with a complaint of "enlarged breasts for 27 months, and elevated blood ß-HCG for 8 months". The clinical data were summarized, and related literature up to March 2022 with the key words"Turner syndrome" "Gonadoblastoma" "Y chromosome" "human chorionic gonadotropin" "precocious" in PubMed, CNKI and Wanfang databases were reviewed. Results: The girl went to the local hospital for 2-month breast development at age of 3 years, and was found with a heart murmur diagnosed with "pulmonary venous malformation and atrial septal defect (secondary foramen type)". Surgical correction was performed. She experienced the progressive breast development, rapid linear growth and markedly advanced skeletal age, which cannot be explained by partial activation in the hypothalamic-pituitary-gonadal axis determined at the age of 3 years and 7 months in local hospital. Then whole-exome sequencing revealed chromosome number abnormality 45, X, which was confirmed by Karyotyping. At the age of 4 years and 6 months, serum ß-HCG was found to be elevated (24.9 U/L) with no lesion found at the local hospital. On physical examination, she was found with breast development, pubic hair development and clitoromegaly with elevated serum testosterone (1.96 µg/L) and ß-HCG (32.3 U/L). Sex determining region Y(SRY) gene was negative in peripheral blood sample. Thoracic and abdominal CT, head and pelvic magnetic resonance imaging were normal. Exploratory laparotomy confirmed the presence of a left adnexal tumor and a right fibrous streak gonad. During surgery, simultaneous samples of bilateral gonadal and peripheral venous blood were obtained and serum ß-HCG, estradiol and testosteron concentrations was higher to lower from left gonadal venous blood, right gonadal venous blood, to peripheral venous blood. Bilateral gonadectomy was performed. Histopathology revealed bilateral gonadoblastomas. SRY was positive in bilateral gonadal tissues. After surgery, serum E2, testerone and ß-HCG returned to normal. So far 4 cases of HCG-secreting gonadoblastoma had been reported worldwide. The phenotypes of the 4 cases were all female, with virilization or amenorrhea, and the preoperative peripheral blood ß-HCG concentrations were 74.4, 5.0, 40 456.0, and 42.4 U/L, respectively. Conclusions: There is a high risk of Gb in TS with Y chromosome components. Gb is infrequently presented with breast development, and Gb associated with HCG secretion is rare. Karyotyping should be performed in a phenotypic female with masculinization, and virilization in TS indicates the presence of Y chromosome material with concurrent androgen secreting tumors.

[Perioperative maternal complications of twin-twin transfusion syndrome after fetoscopic laser photocoagulation].

Objective: To analyze the perioperative maternal complications of twin-twin transfusion syndrome (TTTS) after fetolascopic laser photocoagulation (FLP). Methods: A retrospective study was conducted among 182 cases with TTTS received FLP in Shanghai First Maternity and Infant Hospital from January 2010 to December 2018. The types, incidence and related factors of perioperative maternal complications as well as the changes of maternal laboratory parameters before and after FLP were analyzed. Results: The age of 182 TTTS pregnant women was (29.8±3.9) years old, body mass index (BMI) before pregnancy was (21.3±2.9) kg/m2. The median gestational week of FLP treatment was 22.0 weeks, the preoperative cervical length was (34.1±9.0) mm, and the median preoperative maximum vertical pocket was 12.0 cm. During the perioperative period of FLP treatment, 22 cases (12.1%, 22/182) presented maternal complications, among which 4 cases (2.2%, 4/182) presented severe postoperative maternal complications, including 3 cases of pulmonary edema and 1 case of pulmonary embolism accompanied with right cardiac insufficiency. There were 18 cases (9.9%, 18/182) of common maternal complications during the perioperative period, including 6 cases (3.3%, 6/182) of intraoperative hemorrhage, 5 cases (2.7%, 5/182) of intraoperative amniotic fluid leakage into the pelvic cavity, 5 cases (2.7%, 5/182) of premature rupture of membrane 72 hours after the operation, 1 case (0.5%, 1/182) of inevitable abortion, and 1 case (0.5%, 1/182) of infection. The analysis of related risk factors found that maternal complications were only related to BMI before pregnancy, and the BMI of TTTS pregnant women with complications was lower than that of those without complications, the difference was statistically significant (P<0.01). The hemoglobin level, hematocrit and albumin level of TTTS pregnant women were significantly decreased at 4-6 hours and 24 hours after FLP respectively, compared with those before surgery (P<0.01), and there were no significant correlations with the amount of amniodrainage during surgery (P>0.05 for all). Conclusions: The overall incidence of perioperative maternal complications in the treatment of TTTS by FLP is not high, among which the serious complications mainly include pulmonary edema and pulmonary embolism. Timely correction of maternal hemodilution that may occur in TTTS pregnant women could achieve a good prognosis after FLP.

CircRNA UBAP2 facilitates the progression of colorectal cancer by regulating miR-199a/VEGFA pathway.

OBJECTIVE: The aim of this study is to explore the regulatory mechanism of circRNA UBAP2 (circUBAP2) in colorectal cancer (CRC). PATIENTS AND METHODS: The expression levels of circUBAP2, miR-199a, and VEGFA in tissues and cell lines were detected by RT-qPCR. The cell proliferation was examined by CCK-8 and colony formation assays. The migration and invasion abilities were evaluated by wound healing and transwell assays, respectively. Bioinformatics analysis and Luciferase activity assay were applied to determine the interaction between genes. RESULTS: The expression of circUBAP2 was upregulated in CRC tissues and cell lines, and depletion of circUBAP2 suppressed the cell proliferation, migration, and invasion of CRC. Furthermore, miR-199a inhibitor abrogated the suppressive effect of circUBAP2 knockdown on CRC progression. Vascular endothelial growth factor A (VEGFA) was identified as a downstream target gene of miR-199a, and overexpression of VEGFA rescued the tumor phenotypes attenuated by circUBAP2 knockdown or miR-199a overexpression. CONCLUSIONS: Our findings demonstrated that circUBAP2 facilitated CRC progression by sponging miR-199a to upregulate VEGFA. These findings implied that circUBAP2 may be a potential therapeutic biomarker for CRC.

Lipoxin A4 alleviates lung injury in sepsis rats through p38/MAPK signaling pathway.

The aim of the study was to explore the effect of lipoxin A4 (LXA4) on lung injury in sepsis rats through the p38/mitogen-activated protein kinase (MAPK) signaling pathway. Sprague-Dawley rats were used for the study. The rat model of sepsis-induced acute lung injury was established via cecal ligation (Sepsis group, n=20). LXA4 (0.1 mg/kg) was injected at 6 h after modeling (Treatment group, n=20), and a The Control group (n=20) was also set up. The 7-day survival rate was 100% in The Control group, and LXA4 raised the survival rate of rats in the Sepsis group from 40% to 60% (P<0.01). Alveolar fluid clearance (AFC) significantly declined and the wet/dry weight (W/D) ratio of lung tissues rose remarkably in the Sepsis group compared with those in the Control group, while LXA4 restored AFC and reduced the W/D ratio of lung tissues (P<0.05), suggesting that LXA4 treatment reduces lung fluids and partially enhances AFC, thus lowering the W/D ratio of lung. The total cell count, polymorphonuclear neutrophils (PMN) percentage and concentration of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) were obviously increased in the Sepsis group compared with those in the Control group, while they were markedly decreased in the Treatment group (P<0.05). The activity of myeloperoxidase (MPO) in lung tissue homogenate was evidently higher in the Sepsis group than that in The Control group, while it was notably lower in the Treatment group than that in the Sepsis group after LXA4 treatment (P<0.05). Moreover, it was observed microscopically that the morphology of lung tissues was intact in the Control group. Finally, the results of Western blotting manifested that the p-p38/ MAPK protein expression was remarkably increased in the Sepsis group, indicating the activation of the p38/MAPK pathway, while it was remarkably decreased in the Treatment group, indicating the inhibited activity of the pathway (P<0.05). LXA4 has an anti-inflammatory effect on sepsis rats with lung injury, and such effect is related to the p38/MAPK signaling pathway.

[Effect of fragmented sleep on postoperative cognitive function and central neuroinflammation].

Objective: To investigate the effect of sleep fragmentation on perioperative neurocognitive disorders (PND) and central neuroinflammation by simulating sleep patterns of postoperative patients with sleep fragmentation in aged mice. Methods: Thirty-two elderly ICR mice were randomly divided into four groups (n=8): normal group (C), surgery group (S), fragmented sleep group (F), and surgery+fragmented sleep group (D). Fragmented sleep was conducted after internal fixation of tibia fractures, cognitive function was evaluated by novel object recognition (NOR) and fear conditioning (FC) test, and changes in expression of inflammatory cytokines in hippocampus were detected by ELISA. Results: NOR test: the recognition index (RI) of mice in group C, group S, group F and group D was 0.69±0.07, 0.48±0.07, 0.54±0.10 and 0.50±0.12, respectively. The RI of mice in group S, group F and group D was significantly lower than that in group C (t=4.885, 3.521 and 4.433, all P<0.01). There was no significant difference in RI between group S and group D (t=0.967 1, P>0.05). Contextual FC test: the freezing time of mice in group C, group S, group F and group D was(21.34±6.48), (13.83±4.26), (11.50±6.25) and (6.17±4.77) s, respectively. The freezing time of mice in group S, group F and group D was significantly lower than that in group C (t=2.722, 3.566, 5.496, P<0.05 or P<0.01). The freezing time of mice in group D was significantly lower than that in group S (t=2.774, P<0.05). Cue FC test: the freezing time of mice in group C, group S, group F and group D was (74.36±17.09), (43.91±9.71), (46.34±13.43) and (24.90±14.21) s, respectively. The freezing time of mice in group S, group F and group D was significantly lower than that in group C (t=4.393, 4.043 and 7.136, all P<0.01). The freezing time of mice in group D was significantly lower than that in group S (t=2.743, P<0.05). The levels of TNF-α, IL-6 and IL-1ß in hippocampus of mice in group S, F and D were significantly higher than those in group C, while the levels of TNF-α and IL-6 in hippocampus of mice in group D were significantly higher than those in group S, with statistically significant differences (P<0.05 or P<0.01). Conclusion: Postoperative fragmented sleep aggravates postoperative cognitive impairment and increases the hippocampal neuroinflammation in aged mice.

[Effect of standardized surgical treatment and multidisciplinary treatment strategy on the prognosis of gastric cancer patients: report of a single-center cohort study].

Objective: To explore the effect of standardized surgical treatment and multidisciplinary treatment strategy on the treatment outcomes of gastric cancer patients. Methods: A single-center cohort study was carried out. Clinicopathological and long-term follow up data of primary gastric cancer patients were retrieved from the database of Surgical Gastric Cancer Patient Registry (SGCPR) in West China Hospital of Sichuan University. Finally, 4516 gastric cancer patients were included and were divided into three groups according to time periods (period 1 group: exploration stage of standardized surgical treatment, 2000 to 2006, 967 cases; period 2 group: application stage of standardized surgical treatment, 2007 to 2012, 1962 cases; period 3 group: optimization stage of standardized surgical treatment and application stage of multidisciplinary treatment strategy, 2013 to 2016, 1587 cases). Differences in clinical data, pathologic features, and prognosis were compared among 3 period groups. Follow-up information was updated to January 1, 2020. The overall follow-up rate was 88.9% (4016/4516) and median follow-up duration was 51.58 months. Survival curve was drawn by Kaplan-Meire method and compared with log-rank test. Univariate and multivariate analyses were performed by Cox proportional hazards model. Results: There were significant differences among period 1, period 2 and period 3 groups in the rates of D2/D2+ lymphadenectomy [14.4%(139/967) vs. 47.2%(927/1962) vs. 75.4%(1197/1587), χ(2)=907.210, P<0.001], in the ratio of proximal gastrectomy [19.8%(191/967) vs. 16.6%(325/1962) vs. 8.2%(130/1587), χ(2)=100.020, P<0.001], and in the median intraoperative blood loss (300 ml vs. 100 ml vs. 100 ml, H=1126.500, P<0.001). Besides, the increasing trend and significant difference were also observed in the median number of examined lymph nodes among period 1, period 2 and period 3 groups (14 vs. 26 vs. 30, H=987.100, P<0.001). Survival analysis showed that the 5-year overall survival rate was 55.3% in period 1, 55.2% in period 2 and 62.8% in period 3, and significant difference existed between period 3 and period 1 (P=0.004). The Cox proportional hazards model analysis showed that treatment period (period 3, HR=0.820, 95%CI: 0.708 to 0.950, P=0.008), postoperative chemotherapy (HR=0.696, 95%CI: 0.631 to 0.768, P<0.001) and mid-low gastric cancer (HR=0.884, 95%CI: 0.804 to 0.973, P=0.011) were good prognostic factors. Whereas old age (≥65 years, HR=1.189, 95%CI: 1.084 to 1.303, P<0.001), palliative resection (R1/R2, HR=1.538,95%CI: 1.333 to 1.776, P<0.001), large tumor size (≥5 cm, HR=1.377, 95%CI: 1.239 to 1.529, P<0.001), macroscopic type III to IV (HR=1.165, 95%CI: 1.063 to 1.277, P<0.001) and TNM stage II to IV(II/I:HR=1.801,95%CI:1.500~2.162,P<0.001;III/I:HR=3.588, 95%CI: 3.028~4.251, P<0.001; IV/I: HR=6.114, 95%CI: 4.973~7.516, P<0.001) were independent prognostic risk factors. Conclusion: Through the implementation of standardized surgical treatment technology and multidisciplinary treatment model, the quality of surgery treatment and overall survival increase, and prognosis of gastric cancer patients has been improved.

Adjuvant chemotherapy for patients with gastric neuroendocrine carcinomas or mixed adenoneuroendocrine carcinomas.

BACKGROUND: The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G-NECs) or mixed adenoneuroendocrine carcinomas (G-MANECs). METHODS: The study included patients with G-NECs or G-MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan-Meier method. RESULTS: In total, 804 patients with resectable G-NECs or G-MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no-chemotherapy group. Among patients with G-NECs, survival in the fluorouracil (5-FU)-based chemotherapy group and the non-5-FU-based chemotherapy group was similar to that in the no-chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G-NECs. Among patients with G-MANECs, OS in the non-5-FU-based chemotherapy group was worse than that in the no-chemotherapy group. Patients with G-MANECs did not have better OS when platinum-based chemotherapy was used. CONCLUSION: There was no survival benefit in patients who received adjuvant chemotherapy for G-NECs or G-MANECs.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G-NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G-MANECs). MÉTODOS: Se incluyeron pacientes con G-NECs y G-MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan-Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento. RESULTADOS: En total, se incluyeron en el estudio 804 pacientes con G-NECs y G-MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G-NECs, la supervivencia en los grupos con quimioterapia basada en 5-FU (fluorouracilo) y de quimioterapia sin 5-FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G-NECs. En pacientes con G-MANECs, la OS del grupo con quimioterapia sin 5-FU fue peor que la del grupo sin quimioterapia. Los pacientes con G-MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos. CONCLUSIÓN: La administración de quimioterapia adyuvante en pacientes con G-NECs y G-MANECs no mejoró la supervivencia.

Long-term comparison study of philtral ridge morphology with two different techniques of philtral reconstruction.

Cleft lip and/or cleft palate are the most common congenital craniofacial anomalies. Philtral ridge morphology is an important aesthetic component of unilateral cleft lip (UCL) repair. To this end, we have developed two techniques of philtral ridge reconstruction: (1) asymmetric mattress muscle sutures, and (2) overlapping mattress muscle sutures. The objective of this retrospective cohort study was to compare their outcomes in UCL repairs. Group I patients (n=30) underwent UCL repair before August 2003, including philtral ridge reconstruction by asymmetric mattress muscle sutures. Group II patients (n=30) underwent UCL repair after August 2003, including philtral ridge reconstruction by overlapping mattress muscle sutures. Philtral morphology was evaluated by ultrasonographic and three-dimensional photographic measurements, examining cleft side philtral projection and philtral ridge symmetry. These demonstrated that group II patients had better philtral column symmetry and projection on the cleft side when compared to group I. Overlapping mattress muscle sutures produced better philtral morphology in UCL repairs than asymmetric mattress muscle sutures.

[Modified memory sub-test of Syndrom Kurz test in middle-aged and elderly Chinese].

Objective: To investigate the applicability of the modified memory sub-test of syndrom kurz test (SKT-M) in middle-aged and elderly Chinese. Methods: Between March 1, 2017, and October 31, 2017, at HwaMei Hospital, 132 patients receiving elective great saphenous vein high ligation and stripping operation and 96 their accompanying dependents, 55-75 years old, were randomly divided into the SKT-M group (n=121) and auditory verbal learning test -huashan version (AVLT-H) group (n=107) using random numeral method. The two groups underwent two corresponding neuropsychological tests respectively on the day before surgery and the second day after surgery. Results: There was no significant difference in the baseline characteristics and all the neuropsychological indices at the two time points between patients and dependents (P>0.05). As a consequence, the data of the patients and dependents were integrated to compare the applicability of SKT-M and AVLT-H. The "low-score" ratio of SKT-M immediate recall (2.4%) was lower than that of AVLT-H test (12.1%) (χ(2)=8.138, P<0.01). Besides, the "low-score" ratio of SKT-M delayed recall (5.7%) was also lower than that of AVLT-H test (20.5%) (χ(2)=11.167, P<0.01). The influence factors of SKT-M were less than that of AVLT-H test. However, the learning effect of SKT-M immediate recall was more significant, for its first testing sore (23.1±5.4) was significantly higher than the second one (21.9±5.1) (t=-3.971, P<0.001). Conclusion: The SKT-M has better applicability to 55-75 years old Chinese than AVLT-H test, but its learning effect should be noted.

[Application of digital mandibular movement record and masticatory muscle electromyography in the evaluation of stomatognathic function in patients with mandibular tumor].

OBJECTIVE: To study the clinical characteristics of mandibular movement and masticatory muscle function in preoperative and postoperative patients with unilateral mandibular tumors in the region of mandibular body and ramus by combining digital mandibular movement records with electromyography, and to preliminarily explore the relationship and mechanism between movement and masticatory muscle function. METHODS: Six preoperative patients with tumor in unilateral body and ramus of mandible were included, and three postoperative patients with unilateral segmental resection and reconstruction of mandibular bone were included. The mandibular movement recording system and surface electromyography system were used to collect the movement trajectory of the patients' mandibular marginal movement and chewing movement, and the surface electromyography of bilateral masseter and temporalis was recorded concurrently. The surface electromyography of bilateral masseter and temporalis was collected when the patients were at relaxation and at maximal voluntary clenching (MVC). The motion trajectory was observed on the digital virtual model, and the motion amplitude and direction of mandibular marginal movements were analyzed. The characteristics of masticatory electromyogram (EMG) activity in affected and unaffected sides at relaxation, MVC and bilateral mastication were analyzed, and the asymmetry indexes and activity indexes were calculated. RESULTS: The preoperative mean maximum opening of the patients was (35.20±6.87) mm. Three patients had mild mouth opening limitation, and all the patients' mouth opening trajectory was skewed to the affected side. During lateral movements, the mean range of motion of the affected side [(10.34±1.27) mm] and that of the healthy side [(6.94±2.41) mm] were significantly different. The maximum opening of the postoperative patients was (30.65±17.32) mm, and the mandibular marginal movement characteristics were consistent with those of the patients before surgery. During MVC in the preoperative patients, the median EMG activities of the masseter muscle [44.20 (5.70, 197.90) µV] and the temporalis muscle [42.15 (22.90, 155.00) µV] on the affected side were slightly lower than those of the masseter [45.60 (7.50, 235.40) µV] and the temporalis muscle [63.30 (44.10, 126.70) µV] on the healthy side. In the postoperative patients, individualized changes occurred. Some patients suffered from weakened electromyographic activity on the affected side, while some other ones showed hyperelectromyographic activity on the affected side. CONCLUSION: Both benign and malignant tumors as well as their surgery can cause abnormal mandibular movements and change of electromyographic activity of bilateral masseter and temporalis muscles.

[Effects of remifentanil gradual withdrawal on remifentanil induced postoperative hyperalgesia].

Objective: To explore the effects of remifentanil gradual withdrawal on remifentanil induced postoperative hyperalgesia. Methods: Ninety patients from January to June 2018 undergoing elective laparoscopic hysterectomy under general anaesthesia at Ningbo NO.2 hospital, ASA Ⅰ or Ⅱ grade, aged 20-60, were enrolled in this study and randomly assigned to 3 groups (n=30): Group L (low dose remifentanil), Group H (high dose remifentanil) and Group G (high dose remifentanil with gradual withdrawal). Mechanical pain thresholds (MPT), visual analogue scale (VAS) and additional analgesics were recorded at 6 and 24 hours after the operation. Results: There was no significant difference among the VAS and additional analgesics in three groups at 6 and 24 hours after operation (P>0.05). There was no significant difference among the MPT in three groups before operation (P>0.05). The MPT of group L, group H and group G were (49.8±12.2), (35.5±13.0) and (48.6±11.4) g at 6 hours after surgery, and (51.4±14.3), (36.9±11.1) and (48.8±11.5) g at 24 hours after surgery, respectively, with statistically significant differences (F=12.6, 11.668, both P<0.01). The MPT of group H at 6 h and 24 h after surgery was lower than that of group L (all P<0.01), while the MPT of group G at 6 h and 24 h after surgery was significantly higher than that of group H (all P<0.01). No correlation was observed between MPT and VAS scores or additional analgesics at 6 and 24 hours postoperatively (P>0.05). Conclusion: Remifentanil gradual withdrawal significantly alleviated intraoperative administration of remifentanil induced postoperative hyperalgesia in laparoscopic hysterectomy patients.

[The effect of berberine on ameliorating chronic inflammatory pain and depression].

Objective: To explore the effect of berberine on chronic inflammatory pain and the comorbid depression and the associated mechanisms. Methods: Forty healthy male ICR mice (2 months, 25-30 g) were used in the present study. The chronic inflammatory pain was induced by intraplantar injection of complete freund's adjuvant (CFA) to the hind paws. All animals were divided into 4 groups (n=10 for each group) according to random number table: the saline group (group A), the chronic pain group (group B), the saline+ berberine group (group C) and the chronic pain+ berberine group (group D). The baseline data of pain and depressive performance were measured on the day before any drug treatment.On d1, mice of B and D groups received intraplantar injections of 50 µl CFA emulsion (1∶1 diluted with saline); mice of A and C groups received intraplantar injections of the same volume of saline. During d15-d21, mice of C and D groups received intraperitoneal injections of berberine (50 mg/kg, daily for 7 days); mice of A and B groups received the equal volume of saline. The Hargreaves tests and the Von Frey tests were conducted before the injection of CFA and on d7, d14, d17 and d21 to measure the thermal and mechanical pain thresholds. The forced swimming tests and novelty-suppressed feeding tests were performed before the injection of CFA and on d21 to measure the depressive performance. After the behavioral tests, the levels of inflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) at the lumbar (L4-L5) spinal cord were examined by enzyme-linked immunosorbent assay(ELISA). The mRNA level of chemokine C-C motif ligand 2 (CCL2) in the lumbar spinal cord was examined by quantitative real-time polymerase chain reaction(qRT-PCR). Results: Compared with group A, the thermal withdrawal latency of group B mice on d7, d14, d17, d21 was declined[(3.40±0.67)s vs (10.55±1.58)s, (7.49±1.04)s vs (11.47±1.92)s, (6.46±0.56)s vs (11.60±1.86)s, (6.04±0.54)s vs (10.33±1.59)s, all P<0.01], and the mechanical threshold was also decreased[(0.15±0.03)g vs (0.78±0.24)g, (0.23±0.12)g vs (0.60±0.16)g, (0.30±0.12)g vs (0.72±0.25)g, (0.40±0.00)g vs (0.72±0.19)g, all P<0.01], on d21 the immobility time was increased[(161.60±35.79)s vs (88.92±53.24)s , P<0.05]and the time of feeding latency was decreased[(227.40±57.5)s vs (77.25±26.45)s, P<0.01], suggesting that CFA could induce hyperalgesia and depression. After berberine treatment (daily for 7 days), compared with group B, the thermal withdrawal latency of group D mice was increased[(9.99±2.68)s vs (6.04±0.54)s, P<0.01], the mechanical threshold was elevated[(0.80±0.21)g vs (0.40±0.00)g, P<0.01], the immobility time was decreased[(92.97±44.31)s vs (161.60±35.79)s, P<0.05], and the feeding latency was declined[(105.00±50.00)s vs (227.40±57.5)s, P<0.01]. Compared with group A, the concentrations of spinal IL-1ß, IL-6 and TNF-α in group B were increased[(29.90±4.87)pg/ml vs (21.00±5.46)pg/ml, (131.10±26.12)pg/ml vs (60.68±23.47)pg/ml, (21.54±4.93)pg/ml vs (11.39±3.66) pg/ml , all P<0.01], the mRNA level of CCL2 was upregulated[(2.21±0.60) vs (1.00±0.37), P<0.01]. After berberine treatment (daily for 7 days), compared with group B, the concentrations of IL-1ß, IL-6 and TNF-α in group D were decreased[(19.44±4.83)pg/ml vs (29.90±4.87) pg/ml , (57.82±32.28)pg/ml vs (131.10±26.12)pg/ml , (9.29±2.46)pg/ml vs (21.54±4.93) pg/ml, all P<0.01], the mRNA level of CCL2 was downregulated[(1.33±0.40)vs (2.21±0.60), P<0.05]. Conclusion: Berberine can reverse chronic inflammatory pain induced by CFA and alleviated the comorbid depression. Its anti-nociceptive and anti-depressive effects may associate with downregulation of the spinal levels of the inflammatory cytokines and mRNA transcription of CCL2.

[Brain derived neurotrophic factor enhances the role of mesenchymal stem cells in inhibiting follicular helper T cells].

Objective: To investigate the effect of brain derived neurotrophic factor (BDNF) on mesenchymal stem cells (MSC) inhibiting follicular helper T cells (Tfh cells). Methods: The contents of indoleamine 2,3-dioxygenase (IDO), IL-10, TGF-ß and IL-21 in MSC culture supernatant were detected by ELISA; The peripheral blood of healthy volunteers were collected, and lymphocyte in peripheral blood was separated by human lymphocyte separation solution; Co-cultures of MSC and lymphocyte were performed by Transwell chamber, and the proportion of CD4(+)CXCR5(+) Tfh cells and their subtypes were detected by flow cytometry. Results: ①The concentrations of IL-10, TGF-ß, and IDO in the supernatant of BDNF group (BDNF-stimulated MSC) were higher than those of the control ones (adding PBS with the same volume) [IL-10: (42.1±4.4) ng/ml vs (19.3±2.1) ng/ml, t=4.761, P=0.009; TGF-ß: (13.9±1.7) ng/ml vs (5.3±0.6) ng/ml, t=5.129, P=0.008; IDO: (441.3±56.9) ng/ml vs (226.7±37.6) ng/ml, t=3.130, P=0.035]; ②The comparisons between BDNF (co-culture of lymphocyte and BDNF-stimulated MSC) and MSC groups (co-culture of lymphocyte and MSC) were detailed as of follows: the proportion of CD4(+) CXCR5(+)Tfh cells were lower [(3.37±0.21)% vs (6.51±0.27)%, t=9.353, P<0.001], the proportion of CD4(+) CXCR5(+)CXCR3(+) CCR6(-) Tfh cells were higher [(41.14±2.04)% vs (26.72±2.57)%, t=4.383, P=0.012], CD4(+)CXCR5(+)CXCR3(-)CCR6(-) Tfh2 cells and CD4(+)CXCR5(+)CXCR3(-)CCR6(+) Tfh17 cells were lower [Tfh2: (30.16±5.38)% vs (43.26±4.11)%, t=4.426, P=0.012; Tfh17: (15.61±1.52)% vs (22.32±0.72)%, t=4.202, P=0.014], the proportion of CD4(+)CXCR5(+)Foxp3(+) Tfr cells were higher [(4.95±0.22)% vs (2.32±0.16)%, t=10.241, P<0.001], the concentration of IL-21 in the lymphocyte supernatant was lower [(0.28±0.03) ng/ml vs (0.85±0.08) ng/ml, t=6.675, P=0.003]. Conclusion: BDNF could enhance the inhibitory effect of MSC on Tfh cells through inhibiting the increasing of Tfh cells and the differentiations of Tfh2 and Tfh17 cells.

[Effects of lappaconitine on intraoperative administration of remifentanil induced postoperative hyperalgesia in general anaesthesia patients].

Objective: To explore the effects of lappaconitine on intraoperative administration of remifentanil induced postoperative hyperalgesia in general anaesthesia patients. Methods: One hundred and twenty patients from March to October 2016 undergoing elective thyroid operation under general anaesthesia at Ningbo NO.2 hospital, American Society of Anesthesiologists(ASA) Ⅰ or Ⅱ grade, aged 20-60, were enrolled in this study and randomly assigned to 3 groups (n=40). Remifentanil was intraoperatively infused at 0.1 µg·kg(-1)·min(-1) (Group S) or 0.3 µg·kg(-1)·min(-1) (Groups L and G), and patients in group G received lappaconitine 8 mg 30 minutes before the ending of surgery. Mechanical pain thresholds, visual analogue scale (VAS) and additional analgesics were recorded at 2, 6 and 24 hours after the operation. Results: There was no significant difference among the VAS and additional analgesics in three groups at 2, 6 and 24 h after operation (all P>0.05). There was no significant difference among the mechanical pain thresholds in three groups before and 2 h after operation (all P>0.05). The mechanical pain thresholds of group S, L and G was (45.7±15.6), (35.8±15.0), (47.6±16.4)g at 6 h and (50.7±17.0), (33.7±14.0), (49.7±13.9 )g at 24 h after operation. There was significant difference among the mechanical pain thresholds in group S, L and G at 6 h and 24 h after operation (F=6.586, 16.089, all P<0.01). Compared to group S, the mechanical pain thresholds significantly decreased in group L at 6 h and 24 h after operation (q=2.837, 5.045, all P<0.01). While there was a significantly increase in pain thresholds at 6 h and 24 h postoperatively in group G, as compared with the group L (q=3.384, 4.770, all P<0.01). Conclusion: Lappaconitine significantly alleviated intraoperative administration of remifentanil induced postoperative hyperalgesia in general anaesthesia patients.

[Influence of aluminum chloride exposure on embryonic development of zebrafish and neurobehavior of juvenile fish].

Objective: To investigate the influence of aluminum chloride (AlCl(3)) solution on the embryon-ic development of zebrafish and neurobehavior of juvenile fish. Methods: The embryos of zebrafishat 6 hours after fertilization were exposed to AlCl(3) solution at a concentration of 0, 55.0, 60.5, 66.6, 73.5, 80.5, or 100.0 mg/L, and embryonic hatching rates at 48 and 72 hours after fertilization were calculated. The embryos of zebrafishat 6 hours after fertilization were exposed to AlCl(3) solution at a concentration of 0, 60.0, 72.0, 86.4, 103.7, or 124.4 mg/L, and the embryonic mortality rates at 12, 24, 48, 72, and 96 hours after fertilization were calculat-ed. The embryos of zebrafish at 6 hours after fertilization were exposed to AlCl(3) solution at a concentration of 0, 50, 100, 200, 400, or 800 µg/L, and the changes in the neurobehavior of juvenile fish were observed after hatching, including touch-escape reaction at 72 hours after fertilization and autonomic movement and panic es-cape reflex at 7 days after fertilization. Results: Compared with the 0 mg/L group, the≥66.6 mg/L group had a sig-nificant reduction in embryonic hatching rate at 48 and 72 hours after fertilization, and the ≥72.0 mg/L group had a significant increase in embryonic mortality rate at 96 hours after fertilization (P<0.05) . Compared with the 0 µg/L group, the≥100 µg/L group had a significant reduction in the number of times of touch-escape reaction (P<0.05) .Compared with the 0 and 50 µg/L groups, the 100-800 µg/L groups had significant reductions in total movement distance and average speed (P<0.05) . Compared with the dark period before illumination, all groups had a significant increase in movement speed during the light period of the panic escape reflex test (i.e., the third minute) (P<0.05) ; within 2 minutes after the light was turned off, there was no significant change in movement speed in the 0-200 µg/L groups (P>0.05) ; the 400 and 800 µg/L groups had a significant increase in movement speed (P<0.05) . Conclusion: AlCl(3) exposure may cause embryonic developmental disorder in zebrafish and ab-normal neurobehavior in juvenile fish.

NF-κB/P65 signaling pathway: a potential therapeutic target in postoperative cognitive dysfunction after sevoflurane anesthesia.

OBJECTIVE: This study aimed to explore the role of NF-κB/P65 signaling pathway in postoperative cognitive dysfunction (POCD) after sevoflurane anesthesia. MATERIALS AND METHODS: A total of 120 male Sprague-Dawley (SD) rats were selected and assigned into five groups (24 rats in each group): the control, sevoflurane, sevoflurane + splenectomy, pyrrolidine dithiocarbamate (PDTC, a specific inhibitor of NF-κB), and sevoflurane + splenectomy + PDTC groups. Electrocardiogram (ECoG) and behavior changes of rats were monitored before and after anesthesia/operation. Ionized calcium-binding adapter molecules 1 (Iba-1) in the hippocampal zones were observed by immunofluorescence staining. Blood-brain barrier (BBB) permeability was determined by immunohistochemistry. The mRNA and protein expressions of NF-κB/P65 signaling pathway-related proteins and inflammatory cytokines were detected by qRT-PCR assay and Western blotting. RESULTS: During the anesthesia/operation, the vital signs of rats were stable, but the ECoG in the sevoflurane and sevoflurane + splenectomy groups mainly presented slow waves. The ECoG arousal response in the sevoflurane + splenectomy + PDTC group was observed. At 24 h after the anesthesia/operation, the expressions of NF-κB and P65 in the hippocampal zone, the expressions of IκBα and inflammatory cytokines (IL-1ß, IL-6 and TNF-α), the expression of Iba-1 in rat hippocampal dentate gyrus (DG) zone and CA3 zone, and the permeability of BBB were significantly increased and the behavior of rats changed dramatically (all p < 0.05), while PDTC treatments could eliminate these changes induced by the anesthesia/operation (all p < 0.05). No changes were observed in the expressions of NF-κB, P65, IκBα, Iba-1 and inflammatory cytokines (IL-1ß, IL-6 and TNF-α), and the permeability of BBB and the behavior of rats in the sevoflurane and the PDTC groups (all p > 0.05). CONCLUSIONS: These results suggest that the inhibition of NF-κB/P65 signaling pathway may relieve POCD after sevoflurane anesthesia.