[Postauricular hairline plus temporal approach gasless full-endoscopic parotidectomy for tumors in deep lobe of parotid gland: a 16-case report].

To investigate the safety and feasibility of gasless total endoscopic resection of deep lobe parotid gland tumors via a postauricular hairline plus temporal approach. The approach was designed as: a 4 to 5 cm main incision was designed at the postauricular hairline, and a 0.5 cm auxiliary incision was designed in the temporal hairline. The operating cavity was established with the assistance of a special retractor. "Anterograde" dissection of the facial nerve was performed throughout the procedure, along with partial or total gland removal of the tumor. All 16 operations were successfully completed without conversion to open surgery. During the operation, the trunk and branches of the facial nerve were completely preserved, the tumor was completely removed, and the incision healed. Six patients had mild facial paralysis after operation, and recovered completely after 3 to 6 months. There was no salivary fistula, Frey syndrome, infection, or other complications. The postoperative incision was concealed and the aesthetic effect was good. The postauricular hairline plus temporal approach gasless total endoscopic parotidectomy is safe and feasible. This technique can achieve the complete dissection of the total trunk to the branches of the facial nerve, and has good access to the tumors located in any part of the parotid gland region. On the basis of radical resection of the tumor, it achieves minimally invasive and aesthetic improvement.

MicroRNA-802 promotes the progression of osteosarcoma through targeting p27 and activating PI3K/AKT pathway.

PURPOSE: Increasing evidences suggest dysfunctions of microRNAs (miRNAs) are playing important part in tumors. Therefore, the role of miR-802 in osteosarcoma (OS) was exploited. The object was to evaluate the effect of miR-802 and verify its influence on p27 Kip1 (p27) in OS. METHODS: RT-qPCR experiment was used to detect miR-802 and p27 expression in OS tissues and cells. We explored the function of miR-802 through Transwell assays. The phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase pathway and epithelial-mesenchymal transition (EMT) was detected by Western blot assays. Luciferase assay was used to testify the target of miR-802. RESULTS: MiR-802 expression was elevated in OS, which was related to poor clinical outcome in OS patients. MiR-802 overexpression promoted OS migration, invasion and EMT. Further, p27 is a direct target of miR-802. P27 elevation counteracted the promotion effect of OS on EMT, migration and invasion induced by miR-802. In addition, miR-802 overexpression inactivated PI3K/AKT pathway via targeting p27 in OS. CONCLUSION: MiR-802 promoted the progress of EMT, migration and invasion in OS via targeting p27. This newly identified miR-802/p27/PI3K/AKT axis may represent potential targets for OS.

[Effects of S(+)-ketamine combined with sufentanil for patient-controlled intravenous analgesia on the early recovery in elderly patients undergoing laparoscopic radical resection of rectal cancer].

Objective: To observe the efficacy and safety of S(+)-ketamine combined with sufentanil for patient-controlled intravenous analgesia (PCIA) in elderly patients undergoing laparoscopic radical resection of rectal cancer and explore its impact on patients' early recovery. Methods: One hundred and ten patients undergoing laparoscopic radical resection of rectal cancer in Affiliated Cancer Hospital of Zhengzhou University from December 2020 to March 2021, were divided into two groups (n=55) using a random number table: group S received PCIA, with continuous infusion of S(+)-ketamine combined with sufentanil, while group C received PCIA, with continuous infusion of sufentanil. PCIA was initiated at the end of the surgery, and the formulations were as follows: group S, S(+)-ketamine (1.44 mg/kg), sufentanil (1.05 µg/kg), ketorolac tromethamine (2.0 mg/kg) and tropisetron (5 mg), in 100 ml of normal saline; group C: sufentanil (1.50 µg/kg), ketorolac tromethamine (2.0 mg/kg) and tropisetron (5 mg), in 100 ml of normal saline. Postoperative visual analogue scale (VAS) and Ramsay sedation scale were recorded at 6, 12, 24, 36, 48 h after the surgery. The incidence of remedial analgesia, the effective compressions number of PCI during 48 h after the operation. Time to first ambulation, time to first anal exhaust, time to resume oral feeding were recorded. The occurrence of adverse effects was compared between the two groups. Results: A total of 10 patients were excluded during the study, including 4 cases of conversion to laparotomy, 3 cases of dropping out of the study, and 3 cases with operation time more than 4 hours. Finally, 50 cases in group S and 50 cases in group C completed the study. There were no significant differences in VAS scores and Ramsay sedation sores at all time points between two groups (all P>0.05). Likewise, there were also no significant differences in the number of remedial analgesia and effective compressions of PCIA during 48 h after the operation between the two groups (both P>0.05). The total dosage of sufentanil consumption in group S [(64±9) µg] was lower than that in group C [(95±12) µg] within 48 h of PCIA, with a statistically significant difference (P<0.001). Time to first ambulation in group S was (1.1±0.2) d, which was shorter than that in group C [(1.6±0.5) d], and the difference was statistically significant (P<0.001). Likewise, time to first anal exhaust in group S [(1.3±0.4) d] was shorter than that in group C [(1.8±0.6) d], with a statistically significant difference (P<0.001). Additionally, time to resume oral feeding in group S was (2.5±0.6) d, which was shorter than that in group C [(3.1±0.7) d], and there was a statistically significant difference (P<0.001). The incidence of nausea, vomiting and pruritus in group S were 4.0%, 2.0% and 0, which were lower than that in group C (16.0%, 10% and 8.0%, respectively), with statistically significant differences (all P<0.05). No case with psychiatric symptoms was found in both groups. Conclusion: When used for postoperative intravenous analgesia in elderly patients undergoing laparoscopic radical resection of rectal cancer, S(+)-ketamine combined with sufentanil can provide satisfactory analgesic effects, decrease total consumption of sufentanil and the incidence of adverse effects, and thus facilitate patients' early recovery.

[Clinicopathologic characteristics and causes of difficulty in locating the "difficult to locate" intractable epilepsy].

Objective: To summarize the clinicopathological characteristics of "difficult to locate" intractable epilepsy patients, and investigate the causes of difficulty in their location. Method: Retrospective analysis was performed on the clinical data of 58 patients who underwent resection of the epileptogenic zones after intracranial electroencephalography (iEEG) detection at the Department of Neurosurgery of the First Affiliated Hospital of Fujian Medical University from January 2010 to December 2018. Clinicopathological characteristics and lesion lobes of "difficult to locate" intractable epilepsy were summarized. The prognosis of patients was assessed according to Engel grading.Univariate and multivariate logistic regression analysis were used to investigate the relevant factors affecting the prognosis of patients with "difficult to locate" intractable epilepsy related to malformation of cortical development(MCD). Results: Among the 58 patients, there were 47 cases of MCD (12 cases with mild malformation of cortical development (mMCD), 35 cases with focal cortical dysplasia (FCD)), and 11 cases of other types. Among the 47 MCD cases, univariate analysis showed that patients with preoperative magnetic resonance imaging(MRI) positive and completed resection of the epileptogenic zones had better prognosis (P<0.05). Multivariate analysis indicated that completed resection of epileptogenic zones was an independent factor affecting the postoperative efficacy of MCD (P=0.013,Wald χ(2)=6.149, 95%CI: 0.07-0.56). And among the 47 MCD cases, 18 cases were with mono-lobar lesions and 29 cases were with multi-lobar lesions, however, there was no significant difference of the efficacy between the two groups (P=0.511). Conclusions: MCD, especially FCD, is the main pathological types of patients with "difficult to locate" intractable epilepsy. Multi-lobar pathological changes, especially multi-lobar MCD, are the main reasons of being difficult to locate, however, accurate locating of epileptogenic zones and functional areas via effective use of iEEG can achieve satisfactory efficacy in these patients after resection of the epileptogenic zones.

Randomized clinical trial of intraoperative dexmedetomidine to prevent delirium in the elderly undergoing major non-cardiac surgery.

BACKGROUND: Delirium is common in elderly patients after surgery and is associated with poor outcomes. This study aimed to investigate the impact of intraoperative dexmedetomidine on the incidence of delirium in elderly patients undergoing major surgery. METHODS: This was a randomized double-blind placebo-controlled trial. Elderly patients (aged 60 years or more) scheduled to undergo major non-cardiac surgery were randomized into two groups. Patients in the intervention group received a loading dose of dexmedetomidine 0·6 µg/kg 10 min before induction of anaesthesia followed by a continuous infusion (0·5 µg per kg per h) until 1 h before the end of surgery. Patients in the control group received volume-matched normal saline in the same schedule. The primary outcome was the incidence of delirium during the first 5 days after surgery. Delirium was assessed with the Confusion Assessment Method (CAM) for non-ventilated patients and CAM for the Intensive Care Unit for ventilated patients. RESULTS: In total, 309 patients who received dexmedetomidine and 310 control patients were included in the intention-to-treat analysis. The incidence of delirium within 5 days of surgery was lower with dexmedetomidine treatment: 5·5 per cent (17 of 309) versus 10·3 per cent (32 of 310) in the control group (relative risk (RR) 0·53, 95 per cent c.i. 0·30 to 0·94; P = 0·026). The overall incidence of complications at 30 days was also lower after dexmedetomidine (19·4 per cent (60 of 309) versus 26·1 per cent (81 of 310) for controls; RR 0·74, 0·55 to 0·99, P = 0·047). CONCLUSION: Intraoperative dexmedetomidine halved the risk of delirium in the elderly after major non-cardiac surgery. Registration number: ChiCTR-IPR-15007654 ( www.chictr.org.cn).

ANTECEDENTES: El delirio después de la cirugía es frecuente en los pacientes de edad avanzada y se asocia con malos resultados. El objetivo de este estudio fue investigar el impacto de la administración intraoperatoria de dexmedetomidina en la incidencia de delirio en pacientes mayores sometidos a operaciones de cirugía mayor. MÉTODOS: Se trataba de un ensayo aleatorizado, doble ciego y controlado con placebo. Un total de 620 pacientes mayores (60 años o más) fueron programados para ser sometidos a intervenciones (no cardiacas) de cirugía mayor y se aleatorizaron a dos grupos. Los pacientes en el grupo de intervención recibieron una dosis de carga de dexmedetomidina (0,6 µg/kg, 10 minutos antes de la inducción anestésica) seguida de una infusión continua (0,5 µg/kg/h) hasta 1 h antes de la finalización de la cirugía. Los pacientes del grupo control recibieron el mismo volumen de suero salino siguiendo la misma pauta. El resultado principal era la incidencia de delirio durante los primeros 5 días postoperatorios. Para la valoración del delirio se utilizó el método para la evaluación de la confusión (Confusion Assessment Method, CAM) en pacientes no intubados y el CAM-UCI para los pacientes intubados. RESULTADOS: En total, 309 pacientes que recibieron dexmedetomidina y 310 del grupo control se incluyeron en el análisis por intención de tratar. La incidencia de delirio durante los primeros 5 días tras la cirugía fue inferior en presencia de tratamiento con dexmedetomidina que en ausencia del mismo: 5,5% (17/309) versus 10,3% (32/310); riesgo relativo (RR) 0,53, i.c. del 95% 0,30-0,94, P = 0,026. La incidencia global de complicaciones a los 30 días excluyendo el delirio también fue inferior en presencia que en ausencia de tratamiento con dexmedetomidina (19,4% (60/309) versus 26,1% (81/301), RR 0,74, i.c. del 95% 0,55-0,99, P = 0,047). CONCLUSIÓN: La administración intraoperatoria de dexmedetomidina reduce la presencia de delirio en los pacientes mayores tras cirugía mayor no cardiaca.

Hypoxic preconditioning BMSCs-exosomes inhibit cardiomyocyte apoptosis after acute myocardial infarction by upregulating microRNA-24.

OBJECTIVE: To elucidate the regulatory effect of hypoxic preconditioning bone marrow mesenchymal stem cells (BMSCs)-exosomes on cardiomyocyte apoptosis in acute myocardial infarction (AMI) rats. MATERIALS AND METHODS: BMSCs-derived exosomes were extracted by Exoquick method. Expressions of exosome surface markers were determined by Western blot. The AMI model in rats was established by LAD ligation. Rats were randomly assigned into sham group, AMI group, AMI+H-exo group and AMI+N-exo group. MicroRNA-24 expression in rat myocardium was detected at different time points. Subsequently, hypoxic preconditioning or normoxic preconditioning BMSCs-exosomes were intramyocardially injected into rats. Infarct size was calculated through TTC (triphenyltetrazolium chloride) staining. Cardiomyocyte apoptosis was accessed with Terminal Deoxynucleotidyl Transferase dUTP Nick-end Labeling (TUNEL). Heart function of AMI rats was evaluated by echocardiography. Protein expressions of apoptotic genes in rat myocardium were detected by Western blot. RESULTS: The mRNA level of microRNA-24 was higher in H-exo group than N-exo group. Injection of hypoxic preconditioning BMSCs-exosomes markedly upregulated microRNA-24 level, reduced infarct size and improved cardiac function in AMI rats. Protein expressions of Bax, caspase-3 and cleaved-caspase-3 were downregulated by BMSCs-exosomes treatment. H9c2 cells showed upregulated microRNA-24 level and decreased apoptotic rate after incubation with hypoxic preconditioning BMSCs-exosomes. The above cellular performances were partially reversed by transfection of microRNA-24 inhibitor. CONCLUSIONS: Hypoxic preconditioning BMSCs-exosomes inhibit cardiomyocyte apoptosis in AMI rats by upregulating microRNA-24.

[Association between the morphological classification and prognosis of conservative treatment for vocal fold leukoplakia].

Objective:To explore the association between the morphological classification and prognosis of conservative treatment for vocal fold leukoplakia. Method:Patients with different types of vocal fold leukoplakia received conservative treatment first. Those who had failed response to conservative treatment or recurred received carbon dioxide laser resection. Then the efficacy and recurrence rate were compared among the three types of vocal fold leukoplakia. Result:Two hundred and thirty-six patients consisted of 78 flat and smooth cases, 146 bulge and smooth cases, and 12 rough cases. The complete response rate of conservative treatment for the three types was 80.8%, 65.1%, and 0%, respectively (P<0.01). Out of 158 patients who had complete response to conservative treatment, 10.1% cases recurred in 1 year (flat and smooth vs. bulge and smooth, 6.3% vs. 12.6%,P=0.283). Totally, 78 patients had no complete response to conservative treatment and 16 patients experienced recurrence, whose complete response rate of carbon dioxide resection was 89.5%, 85.7%, and 75.0%, respectively (P=0.53). The pathological results were significantly different among three types. The complete response rate of conservative treatment combined with surgery for three types was 97.4%, 93.8%, and 75.0%, respectively, and the complete response rate of flat and smooth type was significantly higher than that of rough type (P=0.002). Conclusion:The Conservative treatment could be based on the morphological classification of vocal fold leukoplakia. The treatment modality that conservative treatment combined with surgery had no impact on the prognosis of vocal fold leukoplakia.

[Prevalance of peri-anesthesia allergy and its related risk factor: a retrospective survey from 2012-2017].

OBJECTIVE: To investigate the incidence of peri-anesthesia allergy in a tertiary teaching hospital. METHODS: This was a retrospective cohort study. Patients who received anesthesia in operation rooms at Peking University First Hospital from January 2012 to April 2017 were enrolled. Researchers reviewed all the patients' electronic records and screened suspect allergy cases. Allergy was diagnosed according to the definition in Consensus on Management of Perioperative Allergy (China) and Scandinavian Clinical Practice Guidelines on the Diagnosis, Management and Follow-up of Anaphylaxis during Anesthesia. After obtaining the electronic records, two researchers began to screen and supplement missing data according medical records independently, then they checked out each other's data. The final data were reviewed by another two researchers. We collected the patients' basic characteristics, surgery type, anesthesia type, peri-anesthesia use of drugs, prognosis and other data. Univariate logistic regression was employed to screen potential factors of allergy. Factors with statistical significance (P<0.05) in univariate Logistic regression were entered into multivariate Logistic regression to identify independent risk factors of allergy. RESULTS: In the study, 106 074 patients entered final statistic analysis. The incidence of peri-anesthesia allergy was about 1.5/1 000 (156/106 074). The incidence of Grades I, II and III allergy was 64.1% (100/156), 30.1% (47/156), and 5.8% (9/156) respectively. Multivariate logistic regression showed 5 independent risk factors of allergy including history of allergy (OR=6.836, 95%CI: 4.461-10.474, P<0.001), intraoperative use of sufentanil (OR=1.993, 95%CI: 1.228-3.232, P=0.005), intraoperative use of cis-atracuronium (OR=2.495, 95%CI: 1.599-3.893, P<0.001), intraoperative infusion of antibiotics (OR=2.005, 95%CI: 1.375-2.924, P<0.001) and frozen fresh plasma (OR=3.055, 95%CI: 1.842-5.068, P<0.001). CONCLUSION: The incidence of peri-anesthesia allergy is high and further attempt is needed to establish standard operation process of diagnosis and treatment of allergy.

Physiological dissection revealed that both uptake and assimilation are the major components regulating different growth responses of two tobacco cultivars to nitrogen nutrition.

K326 and HD represent major tobacco cultivars in China, which required large N fertiliser input but at different application rates. To understand primary components affecting tobacco N use physiology, we adopted these two varieties as valuable genetic material to assess their growth response to N nutrition. We established a hydroponic culture system to grow plants supplied with different N regimes. Plant biomass, N, ammonium, nitrate, arginine, GS and NR activity, N transfer and use efficiency as well as root uptake were examined. Our data revealed the preference of K326 and HD to utilise nitrate or ammonium nitrate but not ammonium alone, with 2 mm N supply probably sufficient and economical to achieve good biomass production at the vegetative stage. Moreover, both varieties were very sensitive to ammonium, perhaps due to lack of or abnormal signalling related to nitrate and/or arginine rather than impairment of N acquisition and initial assimilation; this was supported by measurements of the plant content of N, ammonium and activities of GS and NR. Notably, short-term 15 N root influx studies identified differential uptake kinetics of K326 and HD, with distinct affinities and transport rates for ammonium and nitrate. The data suggest that the growth adaptation of K326 or HD to higher or lower N may be ascribed to different competences for effective N uptake/translocation and assimilation. Thus, our work provides valuable information to prompt deeper investigation of the molecular basis controlling plant N use efficiency.

TGF-ß1 attenuated branching morphogenesis of embryonic murine submandibular gland through Smad3 activation.

Transforming growth factor-ß1 (TGF-ß1) plays several crucial regulatory roles in multiple physiological and pathological processes. The aim of this work was to investigate the role of TGF-ß1 in branching morphogenesis of salivary gland. We harvested and cultured submandibular salivary glands (SMGs) from murine embryos, which were then treated with exogenous TGF-ß1, or its neutralized antibody, Smad3 inhibitor, or Smad3 small interfering RNA (siRNA). Our results suggested that TGF-ß1 attenuated branching morphogenesis of embryonic murine SMG via Smad3 activation, thus playing a negative regulatory role in salivary gland development.

Interferon-γ affects leukemia cell apoptosis through regulating Fas/FasL signaling pathway.

OBJECTIVE: Imbalance of hematopoietic cell proliferation and apoptosis is one of the major causes of leukemia. Enhanced cell proliferation and reduced apoptosis lead to hemocytes accumulation. Fas/FasL signaling pathway promotes cell apoptosis. This study investigated the impact of interferon γ (IFN-γ) on chronic myelogenous leukemia cell proliferation and apoptosis to elucidate its interaction with Fas/FasL signaling pathway. PATIENTS AND METHODS: Leukemia K562 cells were routinely cultivated and treated with 10 U/ml, 100 U/ml, and 1000 U/ml interferon for 12 h, 24 h, and 48 h, respectively. MTT assay was applied to test cell proliferation. TUNEL assay was adopted to determine cell apoptosis. Western blot was selected to detect Fas/FasL expression. RESULTS: Different concentrations of IFN-γ inhibited cell proliferation at various time points. IFN-γ at 1000 U/ml treatment for 48 h exhibited the strongest suppressive effect on cell proliferation (p < 0.05). IFN-γ intervention enhanced K562 cell apoptosis with concentration and time dependence (p < 0.05). Fas and FasL proteins expressions upregulated after treated by IFN-γ following dose elevation and time extension (p < 0.05). CONCLUSIONS: IFN-γ inhibits leukemia K562 cell proliferation and promotes cell apoptosis via facilitating Fas and FasL proteins expressions.

The dual roles of Armigeres subalbatus prophenoloxidase V in parasite melanization and egg chorion melanization in the mosquito Ar. subalbatus.

Phenoloxidases (POs) play key roles in various physiological functions in insects, e.g., cuticular sclerotization, wound healing, egg tanning, cuticle formation and melanotic encapsulaction of pathogens. Previously, we identified five POs, designated As-pro-PO I-V, from the mosquito Armigeres subalbatus and demonstrated that the functions of As-pro-PO I, II and III, were associated with filarial parasite melanization, blood feeding and cuticle formation, respectively. In the present study, we delineate the dual functions of As-pro-PO V. We found that the level of As-pro-PO V mRNA in mosquitoes was significantly increased after microfilaria challenge or blood feeding, and decreased to normal level after oviposition. Knockdown of As-pro-PO V by dsRNA resulted in significant decreases in the degree of microfilaria melanization, egg chronic melanization rates and egg hatching rates in Ar. subalbatus. Further transfection and electrophoretic mobility-shift assays verified the As-pro-PO V gene might regulated by both AP-1, a putative immune-related regulatory element and CdxA, a developmental regulatory element. The binding of AP-1 and CdxA motif with mosquito nuclear extracts was significantly enhanced after microfilaria challenge and blood-feeding in Ar. subalbatus, respectively. These results indicate that As-pro-PO V is a critical enzyme that is required for both an effective melanization immune response and egg chorion melanization in this mosquito.

Computed tomography versus magnetic resonance imaging for diagnosing cervical lymph node metastasis of head and neck cancer: a systematic review and meta-analysis.

Computed tomography (CT) and magnetic resonance imaging (MRI) are common imaging methods to detect cervical lymph node metastasis of head and neck cancer. We aimed to assess the diagnostic efficacy of CT and MRI in detecting cervical lymph node metastasis, and to establish unified diagnostic criteria via systematic review and meta-analysis. A systematic literature search in five databases until January 2014 was carried out. All retrieved studies were reviewed and eligible studies were qualitatively summarized. Besides pooling the sensitivity (SEN) and specificity (SPE) data of CT and MRI, summary receiver operating characteristic curves were generated. A total of 63 studies including 3,029 participants were involved. The pooled results of meta-analysis showed that CT had a higher SEN (0.77 [95% confidence interval {CI} 0.73-0.87]) than MRI (0.72 [95% CI 0.70-0.74]) when node was considered as unit of analysis (P<0.05); MRI had a higher SPE (0.81 [95% CI 0.80-0.82]) than CT (0.72 [95% CI 0.69-0.74]) when neck level was considered as unit of analysis (P<0.05) and MRI had a higher area under concentration-time curve than CT when the patient was considered as unit of analysis (P<0.05). With regards to diagnostic criteria, for MRI, the results showed that the minimal axial diameter of 10 mm could be considered as the best size criterion, compared to 12 mm for CT. Overall, MRI conferred significantly higher SPE while CT demonstrated higher SEN. The diagnostic criteria for MRI and CT on size of metastatic lymph nodes were suggested as 10 and 12 mm, respectively.

A systematic review and meta-analysis on the efficacy of low-level laser therapy in the management of complication after mandibular third molar surgery.

The successful reduction of postoperative discomfort is of great significance. This review aims to evaluate the efficacy of low-level laser therapy (LLLT) for the reduction of complication caused by impacted mandibular third molars extraction. An extensive literature search up to October 2013 for randomized controlled trials (RCTs) was performed through CENTRAL, PubMed, Embase, Medline, and CNKI. Six RCTs in which involves 193 participants are included in the meta-analysis. Among them, three RCTs exhibit a moderate risk of bias, while the other three show a high bias risk. Compared with placebo laser/control group, pain is significantly reduced with LLLT on the first day (mean difference [MD] = -2.63, 95% confidence interval [CI] -4.46 to -0.79, P = 0.005). The superiority of LLLT in pain control persists on the second day (MD = -2.34, 95% CI -4.61 to -0.06, P = 0.04) and the third day (MD = -3.40, 95% CI -4.12 to -2.68, P < 0.00001). Moreover, LLLT reduces an average of 4.94 mm (MD = 4.94, 95 % CI 1.53 to 8.34, P = 0.004) of trismus compared with placebo laser irradiation in the first 3 days. On the seventh day, the superiority of LLLT also persists (MD = 3.24, 95% CI 0.37 to 6.12, P = 0.03). In the first 3 days after surgery, extraoral irradiation (MD = -0.69, 95% CI -1.30 to -0.08, P = 0.03) and intraoral combined with extraoral irradiation (MD = -0.65, 95% CI -1.15 to -0.15, P = 0.01) reduced facial swelling significantly. On the seventh day, the intraoral combined with extraoral irradiation group (MD = -0.32, 95% CI -0.59 to -0.06, P = 0.02) still showed benefit in relieving facial swelling. However, because of the heterogeneity of intervention and outcomes assessment and risk of bias of included trials, the efficacy is proved with limited evidence. In the future, well-designed RCTs with larger sample size will be required to provide clearer recommendations.

Efficacy of low-level laser therapy in the management of orthodontic pain: a systematic review and meta-analysis.

This review aimed to identify the efficacy of low-level laser therapy (LLLT) in the management of orthodontic pain. This systematic review and meta-analysis was carried out in accordance with Cochrane Handbook and the PRISMA statement. An extensive literature search for RCTs, quasi-RCTs, and CCTs was performed through CENTRAL, PubMed, Embase, Medline, CNKI, and CBM up to October 2011. Risk of bias assessment was performed via referring to the Cochrane tool for risk of bias assessment. Meta-analysis was implemented using Review Manager 5.1. As a result, four RCTs, two quasi-RCTs, and two CCTs were selected from 152 relevant studies, including 641 patients from six countries. The meta-analysis demonstrated that 24% risk of incidence of pain was reduced by LLLT (RR = 0.76, 95% CI range 0.63-0.92, P = 0.006). In addition, compared to the control group, LLLT brought forward "the most painful day" (MD = -0.42, 95% CI range -0.74- -0.10, P = 0.009). Furthermore, the LLLT group also implied a trend of earlier end of pain compared with the control group (MD = -1.37, 95% CI range -3.37-0.64, P = 0.18) and the pseudo-laser group (MD = -1.04, 95% CI range -4.22-2.15, P = 0.52). However, because of the methodological shortcomings and risk of bias of included trials, LLLT was proved with limited evidence in delaying pain onset and reducing pain intensity. In the future, larger and better-designed RCTs will be required to provide clearer recommendations.

Enhanced SCN7A/Nax expression contributes to bone cancer pain by increasing excitability of neurons in dorsal root ganglion.

Bone pain is one of the most common complications in cancer patients with bone metastases, and has the most significant impact on quality of life for patients. Patients with bone cancer pain may be difficult to treat due to the poor understanding of the mechanisms; therefore, the mechanisms of bone cancer pain required elucidation for developing new therapeutics. Recent studies show that SCN7A/Nax channel serves as a sodium-level sensor of the body fluid that controls the Na-intake behavior by changing the excitability of neurons. In the current study, the expression of SCN7A/Nax and the excitability of primary sensory neurons in bone cancer pain rats were examined. The analgesic effects of knockdown SCN7A/Nax channel using RNAi lentivirus intrathecal treatment were evaluated with a behavioral test. The results showed that implantation of sarcoma induced ongoing and movement-evoked pain behaviors, whereas SCN7A/Nax knockdown prevented the onset of these hyperalgesia. Immunohistochemistry showed that SCN7A/Nax was located in the medium- to large-sized neurons in dorsal root ganglions (DRGs). The proportion of SCN7A/Nax-positive cells was significantly increased in DRGs ipsilateral to sarcoma implantation. Immunostaining results were further confirmed by Western blot and real time-polymerase chain reaction (RT-PCR) analyses. Recording from primary sensory neurons in excised rat dorsal root ganglias, we found that most of SCN7A/Nax-positive neurons exhibited subthreshold oscillations, depolarized resting membrane potential and more negative threshold of action potential. These electrophysiological changes of neurons increased ectopic spike discharge which was thought to be an important generator of chronic pain, however, the hyperexcitability was completely reversed by SCN7A/Nax knockdown. These results demonstrate that enhanced expression of SCN7A/Nax channel within distinct subpopulation of DRG neurons contributes to bone cancer pain by increasing the excitability of these neurons. These findings may lead to novel strategies for the treatment of bone cancer pain.

Relationship between apoptosis and proliferation in granulosa and theca cells of cystic follicles in sows.

To investigate the causes of the occurrence and persistence of porcine cystic follicles, we evaluated the apoptosis and proliferation of follicular cells in these cysts. Apoptotic frequencies were examined by TUNEL assay and the expression of apoptosis regulators (XIAP, bax, bc1-2 and caspase-3) by immunohistochemistry, Western blotting and real-time quantitative PCR; cell proliferation activity was evaluated by PCNA immunohistochemistry and proliferation of in vitro cultured granulosa and theca cells. The low apoptotic frequency and weak proliferative activity were found in cystic follicles. Low frequency of apoptosis might be associated with decreased amounts of apoptotic-related factors (bax and caspase-3) and increased amounts of anti-apoptotic factors (XIAP and bcl-2) in cystic follicles. Significantly lower proliferation activity was detected in granulosa and theca cells from cystic follicles, and lesser PCNA-positive cells were found in cystic follicles. Our results indicate that the programmed cell death and cell proliferation system were altered in cystic follicles. The disorder between apoptosis and proliferation was responsible for maintaining a static condition without degeneration, which leads to the long-term persistence of follicles. These findings provide important novel insights into the pathogenesis of follicular cysts in sows.

Comparative proteomic analysis of follicular fluids from normal and cystic follicles in sows.

Follicular fluid (FF) includes various biologically active proteins which can affect follicular growth and maturation. Certain proteins could reflect the physiological and pathological status of follicles. The aim of the present study was to explore the key proteins associated with pathogenesis of follicular cysts, some of which may be candidate biomarkers for the condition. We analysed the proteomes of FF from small, medium, large and cystic follicles by two-dimensional electrophoresis (2-DE) combined with mass spectrometry (MS). The protein components in FF were found to be significantly different among groups; about 300 proteins spots in each group were examined, and 32 differentially expressed proteins were identified from different groups. To further reveal the source of identified proteins, transcripts encoding two of these, transferrin and RBP-4, were detected in granulosa cells (GCs) by RT-PCR, as well as the proteins were detected in 24 h culture media of GCs by ELISA. High levels of RBP-4 were examined in FF of cystic follicles by 2-DE analysis, which were significantly different to those in large follicles (p < 0.05). In conclusion, the study enriches our understanding of the proteins of FF; RBP-4 and transferrin originate from passive transfer and follicular synthesized secretion, and RBP-4 might be a candidate biomarker for porcine follicular cysts. Combined with histological studies, these results further suggest that changes of the type and quantity of proteins in FF might be attributed to an abnormal metabolism of follicular cells and structure of follicular wall in cystic follicles. Our findings will contribute to further insight into the pathogenesis of follicular cysts.

Modeling the effects of estradiol and progesterone on the acute phase proinflammatory axis: variability in tumor necrosis factor-α, nitric oxide, and xanthine oxidase responses to endotoxin challenge in steers.

The severity of host response in some diseases differs between sexes, and this dimorphism has been attributed to the immunomodulating effects of reproductive steroid hormones. In females, susceptibility to disease stress has been associated with reproductive status and attributed to prevailing progesterone (P4) or estrogen concentrations during different estrous cycle phases. Our objective was to clarify and define the effect of P4 or 17ß-estradiol (E2) on the acute proinflammatory component of the innate immune system by administering these hormones to steers and evaluating initial and tolerance-associated concentration patterns of circulating proinflammatory immune response mediators after two consecutive lipopolysaccharide (LPS) challenges (LPS1 and LPS2, 6 d apart; 2.5 µg/kg BW, intravenously, Escherichia coli 055:B5). Plasma concentrations of the proinflammatory initiation cytokine tumor necrosis factor-α (TNF-α), nitrate+nitrite [NO(x), estimate of nitric oxide (NO) production], haptoglobin (HG; acute phase protein) and plasma xanthine oxidase activity (mediator of superoxide production) were measured. Crossbred steers (392 ± 7 kg) were fed a forage-concentrate diet (15% CP) to appetite and assigned to control (C; n = 7), P4 (n = 8), or E2 (n = 5) treatment. Jugular blood samples were obtained at 0, 1, 2, 3, 4, 7, and 24 h relative to each of the two LPS injections. For each proinflammatory biomarker, the area under the time by concentration curve (AUC) was used to evaluate and compare responses to the LPS challenge. Treatment with E2 disrupted LPS tolerance as observed in augmented plasma TNF-α (P < 0.01) and NO(x) (P < 0.01) responses to LPS2. Compared with C, P4 treatment decreased plasma NO(x) AUC after LPS2 (P < 0.05) and tended to reduce TNF-α AUC after LPS1 (P = 0.08). Plasma xanthine oxidase activity AUC was increased (P < 0.01) over C by E2 treatment after both LPS1 and LPS2. HG response to LPS1 within 24 h was not affected by any treatment. However, 6 d after LPS1 plasma HG concentration remained higher (P < 0.01) in steers treated with E2 than with C or P4. Results indicate that in cattle, P4 and E2, respectively, attenuate or amplify the response to LPS challenge at several points critical to the regulation of the progression of the proinflammatory cascade.

Gene therapy for cancer: bacteria-mediated anti-angiogenesis therapy.

Several bacterial species have inherent ability to colonize solid tumors in vivo. However, their natural anti-tumor activity can be enhanced by genetic engineering that enables these bacteria express or transfer therapeutic molecules into target cells. In this review, we summarize latest research on cancer therapy using genetically modified bacteria with particular emphasis on blocking tumor angiogenesis. Despite recent progress, only a few recent studies on bacterial tumor therapy have focused on anti-angiogenesis. Bacteria-mediated anti-angiogenesis therapy for cancer, however, is an attractive approach given that solid tumors are often characterized by increased vascularization. Here, we discuss four different approaches for using modified bacteria as anti-cancer therapeutics--bactofection, DNA vaccination, alternative gene therapy and transkingdom RNA interference--with a specific focus on angiogenesis suppression. Critical areas and future directions for this field are also outlined.