Objective To observe the effect of Ginkgo biloba extract(GBE)on depression like behavior in post stroke depression(PSD)model rats,and explore the mechanism of regulating Toll like receptor 4/nuclear factor-κ B(TLR4/NF-κB)pathway to inhibit neuroinflammation.Methods Rats were randomly divided into 6 groups,sham,cerebral ischemia,PSD,paroxetine,low-dose Ginkgo biloba extract(GBE-L)and high-dose Ginkgo biloba extract(GBE-H)groups,10 rats in each group.Except for the sham group,middle cerebral artery occlusion(MCAO)was performed to prepare a left focal cerebral ischemia model.Except for the sham group and cerebral ischemia group,other groups were subjected to chronic unpredictable mild stress(CUMS)to establish PSD rat model for 8 weeks.After 4 weeks of CUMS,the paroxetine group,GBE-L,and GBE-H were treated with paroxetine 5 mg·kg-1,GBE 50 mg·kg-1,and GBE 100 mg·kg-1,respectively.The sham group,cerebral ischemia group,and PSD group were treated with the same volume of 0.9％NaCl and continuously administered by gavage for 28 d.After 4 weeks and 8 weeks of CUMS,the body weight and sugar preference test were measured.Levels of serum tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β)and levels of norepinephrine(NE),serotonin(5-HT),and dopamine(DA)in the cerebral cortex were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of Tlr4,Nfkb1,and nuclear factor κ B-kinase subunit β inhibitory factor(Ikbkb)in the hippocampus of rats were detected by polymerase chain reaction.The protein levels of NF-κB,nuclear factor κB inhibitory protein α(IKBα)and phosphorylation nuclear factor κB inhibitory protein α(p-IKB)in hippocampal tissue were detected by Western blot.Results The body weights of rats in the sham group,cerebral ischemia group,PSD group,paroxetine group,GBE-L group and GBE-H group were(427.10±6.36),(403.10±7.37),(310.10±9.71),(355.00±4.03),(347.90±9.88)and(391.90±5.07)g;sugar preference rate were(93.93±1.78)％,(91.57±1.03)％,(54.72±7.34)％,(88.35±4.36)％,(63.55±12.73)％and(81.04±4.31)％;the levels of NE in the cerebral cortex were(1 951.14±52.86),(1 827.27±23.63),(1 662.12±35.92),(2 033.58±72.28),(1 887.31±33.07)and(2 175.00±42.54)pg·mL-1;the levels of 5-HT in the cerebral cortex were(237.07±8.86),(226.15±10.27),(214.51±3.46),(297.13±5.79),(274.14±7.63)and(285.34±8.72)ng·mL-1;the levels of DA in the cerebral cortex were(1 531.11±47.26),(1 209.89±58.09),(1 143.15±36.31),(1 812.67±51.28),(1 651.56±31.82)and(1 853.33±20.42)pg·mL-1.Compared with the PSD group,GBE significantly increased the body weight of rats(P＜0.01)and increased the preference rate of sugar water in rats,showing the antidepressant like behavioral.GBE significantly reduced the levels of serum TNF-α,IL-1 β(all P＜0.01),increased the levels of NE,5-HT,and DA in the cerebral cortex(all P＜0.01),down regulate the mRNA levels of Tlr4,Nfkb1 and Ikbkb(P＜0.05,P＜0.01),reduced the expression of NF-κB(P＜0.01),and reduced the phosphorylation of IKBα(P＜0.01).Conclusion Ginkgo biloba extract can improve depression-like behavior in PSD model rats,and has antidepressant effect.Its mechanism is related to the inhibition of TLR4/NF-κB pathway,thus reducing neuroinflammation.

A high performance liquid chromatography (HPLC) method utilizing correction factors was established for the quantitative detection of related substances in flumazenil. Separation was achieved using an Agilent Pursuit XRs C18 column (250 mm × 4.6 mm, 5 μm) with an isocratic elution of dilute phosphoric acid, methanol, and tetrahydrofuran as the mobile phases. Correction factors calculated from a standard curve method were applied to determine the impurity content. The quantification of impurities in flumazenil was conducted using both external standard and correction factor methods, followed by validation and comparison of the two. For the identification of degradation products, a forced degradation approach was employed to prepare a flumazenil degradation solution, and the resulting impurities were confirmed by LC-MS analysis. The separation of flumazenil and its impurities was found to be efficient. The limits of quantification for impurities A, B, D, and E were established at 0.169 9, 0.314 7, 0.143 9, and 0.270 8 ng, respectively, with the limits of detection at 0.055 8, 0.096 9, 0.048 8, and 0.089 0 ng. These impurities demonstrated a strong linear relationship across the concentration ranges of 0.034 9-7.847 0, 0.038 7-8.710 7, 0.034 6-7.794 1, and 0.032 4-7.292 8 µg·mL^-1, respectively (n = 7). The method achieved average recoveries between 98.25% and 99.42%, with an RSD of less than 2.0% (n = 9), indicating high accuracy. The external standard and correction factor methods were used to determine the related substances in flumazenil, and the results of the two methods were consistent. The established HPLC method is characterized by its high accuracy, sensitivity, and repeatability, and is suitable for determining related substances in flumazenil.

Objective:To compare the aortic remodeling of the Fabulous stent system and standard thoracic aortic endovascular repair (TEVAR) on distal aorta type B aortic dissection (TBAD). Methods:The prospective data collected between Dec 2017 and Oct 2019 from 134 patients with type B aortic dissection (TBAD) who underwent treatment with the "Fabulous" stent system, and retrospective data from 159 TBAD patients receiving standard TEVAR from corresponding multicenter. By using propensity score matching analysis, we compared the prognosis and aortic remodeling outcomes in patients undergoing Fabulous and standard TEVAR treatments during a 1-year postoperative follow-up.Results:In this study, 62 patients in Fabulous group and 62 patients in standard TEVAR were included.There were no significant statistical differences in baseline characteristics between the two groups. In terms of aortic remodeling in bare stent region, Fabulous group had better change trends of diameter of true lumen [10.6 (4.4, 14.5) mm vs. 4.7 (0.9, 10.7) mm, P=0.001] and false lumen [-24.2 (-30.5, -4.9) mm vs. 0.7 (-11.8, 2.3) mm, P<0.001] than those in the standard TEVAR group. The rate of complete false lumen thrombosis was also higher in the Fabulous group (62.9% vs. 37.1%, P=0.042). Conclusion:The Fabulous stent system, when compared to standard TEVAR surgery, demonstrates good aortic remodeling outcomes in the distal aorta.

ObjectiveTo analyze the induction effect of Fusobacterium nucleatum （Fn） on endoplasmic reticulum stress-related proteins Glucose-regulating protein 78（GRP78） and X-box binding protein 1（XBP1） in esophageal squamous cell carcinoma （ESCC）， and to explore its potential mechanism and clinical significance. MethodsESCC cells KYSE150 and KYSE140 were infected with Fn for 12 h， 24 h and 48 h. The oxidative stress indexes （ROS， MDA and SOD） and the expression of GRP78 and XBP1 in each group were detected by oxidative stress index kit and Western blot. The experiment was divided into Fn groups， Fn+siNC1 groups， Fn+siGRP78 groups， Fn+siNC2 groups and Fn+siXBP1 groups； the oxidative stress indexes， paclitaxel （PTX） response efficacy， abilities of proliferation， invasion and metastasis in each group were compared. The infection of Fn and the expression of GRP78 and XBP1 in 234 ESCC and paracancerous tissues were detected by RNA scope and immunohistochemistry. The correlation between each factor and clinicopathological characteristics of patients was analyzed by Chi-square test. The influence of each factor on the survival of patients was compared by Kaplan-meier survival estimate. ResultsCompared with Fn uninfected KYSE150 and KYSE140 cells， the content of ROS and MDA was gradually increased， the activity of SOD was gradually decreased， and the expression of GRP78 and XBP1 was gradually increased in Fn infected groups （12 h， 24 h and 48 h） （P < 0.05）. Compared with Fn groups， Fn+siNC1 groups， and Fn+siNC2 groups， ROS and MDA contents were decreased， SOD activity was increased， PTX response efficacy was enhanced， and abilities of proliferation， invasion and metastasis were decreased in Fn+siGRP78 and Fn+siXBP1 groups （P < 0.05）. The rates of Fn， GRP78 and XBP1 in ESCC tissues were 43.16%， 69.66% and 60.68%， respectively. And the three indexes were significantly consistent （P < 0.05）. The patients with positive Fn infection and high expression of GRP78 and XBP1 were mostly males with a history of smoking and drinking， and the tumor differentiation degree was low， the invasion degree was deep， the lymph node metastasis rate was high， and the clinical stage was mostly stage Ⅲ/Ⅳ. The 5-year survival time of patients with above positive indexes was shortened （P < 0.05）. ConclusionsFn could induce endoplasmic reticulum stress by inducing the high expression of GRP78 and XBP1， and promote the malignant evolution of ESCC.

Objective:To evaluate the clinical efficacy and safety of Longmu Zhuanggu granule for the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency. Method:This multicenter stratified， block-randomized， double-blind， double-dummy， positive drug （pidotimod granule） parallel controlled， and non-inferiority trail intended to included 240 children patients and divided them into the experimental group （n=120） and the control group （n=120） at the ratio of 1∶1. Patients in both groups were treated for eight successive weeks and followed up for 12 months. The cure rates， numbers of respiratory infections， average courses of disease， curative effects of traditional Chinese medicine （TCM） syndrome， curative effects of individual symptoms， curative effects of immune indexes， and safety indexes between the two groups were observed and compared. Result:A total of 237 subjects were collected from 10 research centers， including 119 cases in the control group and 118 in the experimental group. There were 236 cases enrolled into the full analysis set （FAS）， 210 into the per-protocol set （PPS）， and 236 into the safety set （SS）. The baseline data of the two groups were not significantly different from each other， indicating that they were comparable. The cure rates of the experimental group and control group were 75.21% （88/117） and 73.95%（88/119）， respectively， with the 95% confidence interval （CI） of difference between the two groups being 1.26% （-9.85%，12.37%） for FAS and 3.81% （-6.28%，13.90%） for PPS. The 95% CI fell within the 10% non-inferiority margin， implying that non-infertility test of the cure rate in the treatment of endpoint disease was valid， and the conclusions of FAS and PPS analysis were consistent. There was no significant difference in the number or course of upper respiratory infection， bronchitis， and pneumonia. The difference in curative effects of TCM syndrome between the two groups after four weeks of treatment was not remarkable. After eight weeks of treatment， the total effective rate of the experimental group was 84.62%（99/117）， statistically higher than 78.15%（93/119） of the control group（χ²=-3.26，P<0.05）. There were no significant differences in the disappearance rates of individual symptoms between the two groups after four weeks of treatment. After eight weeks of treatment， the experimental group and control group exhibited the disappearance rates of 67.50%（54/80） and 47.37%（36/76） for shortness of breath and laziness to speak， 75.00%（54/72） and 53.33%（40/75） for poor appetite， 54.55%（60/110） and 37.84%（42/111） for hyperhidrosis， respectively， with obviously better outcomes observed in the experimental group （P<0.05，P<0.01）. The inter-group comparison revealed significant differences in immune indexes after eight weeks of treatment. As demonstrated by comparison with the situations before treatment， IgA， IgG， IgM， and CD4 did not change significantly after treatment. Except for CD8 in the experimental group (P<0.05), there was no significant difference in other immune indexes before and after treatment There was no significant difference in the incidence of adverse reactions. Conclusion:Longmu Zhuanggu granule is not inferior to pidomod granule in the treatment of children recurrent respiratory infection due to lung-spleen Qi deficiency， and it exhibits good safety， implying its promising clinical application value.

OBJECTIVE: To observe the protective effect of electroacupuncture (EA) at Neiguan (PC 6) on pulmonary function during one-lung ventilation (OLV) in patients with lobectomy, and explore its action mechanism. METHODS: Sixty patients with lobectomy were randomly divided into an observation group and a control group, 30 cases in each one. The patients in the control group were treated with general anesthesia, and OLV was given when surgery began; when the surgery finished, air was removed from the thoracic cavity and two-lung ventilation was performed. On the basis of the treatment in the control group, the patients in the observation group were treated with EA (disperse-dense wave, 2 Hz/100 Hz of frequency) at Neiguan (PC 6) 30 min before anesthesia induction until the end of the surgery. The pulmonary function indexes [arterial partial pressure of oxygen (PaO RESULTS: Compared with T CONCLUSION EA at Neiguan (PC 6) has protective effects on lung injury induced by OLV after lobectomy, and its mechanism may be related to the improvement of oxidative stress and inflammatory response.
Anesthesia, General ; Electroacupuncture ; Humans ; Lung ; Lung Injury ; One-Lung Ventilation

OBJECTIVE: To compare the orofacial pain sensitivity with operant test and mechanical hyperalgesia with von Frey filaments of two orofacial pain models (EOI: experimental occlusal interference; pIONX: partial infraorbital nerve transection). To investigate the operant and evoked characteristics of EOI-rats. METHODS: The orofacial operant behaviors were tested by Ugo Basile Orofacial Stimulation Test System. The mechanical thresholds of vibrissal pads were tested by von Frey filaments. Male Sprague-Dawley rats were randomly divided into eight groups: von Frey group: sham-EOI, EOI, sham-pIONX, pIONX (sham: sham-operated group); operant test group: sham-EOI, EOI, sham-pIONX, pIONX (sham: sham-operated group). The mechanical thresholds and orofacial operant behaviors were tested on pre-operation and post-operation days l, 3, 7, 10, 14 and 21. RESULTS: In pIONX of von Frey group, the mechanical withdrawal threshold decreased from days 1 to 21 (P<0.05), peaking from days 7 to 10, and lasted until the end of the experiment. There was no significant difference between the bilateral sides. In pIONX of operant test group, the total contact time decreased from days 10 to 21 (P<0.05), peaking from days 10 to 14, and lasted until the end of the experiment. In EOI of von Frey group, the mechanical withdrawal threshold decreased from days 3 to 21 (P<0.05), peaking on day 7, and lasted until the end of the experiment. There was no significant difference between the bilateral sides. In EOI of operant test group, the total contact time decreased from days 1 to 21 (P<0.05), peaking from days 7 to 10, and lasting until the end of experiment. CONCLUSION Orofacial operant test is a stable method to evaluate orofacial pain behaviors, which could discriminate the feature of neuropathic and EOI orofacial pain. In these two animal models, both of the operant behaviors and the mechanical hyperalgesia exhibited different time courses. Orofacial operant test provides a novel method for evaluating the orofacial pain sensitivity and studying the orofacial pain mechanism thoroughly.
Animals ; Disease Models, Animal ; Facial Pain ; Hyperalgesia ; Male ; Pain Threshold ; Rats ; Rats, Sprague-Dawley

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE: To investigate the effect of long-term resistance exercise of hindlimb on mechanical hyperalgesia of bilateral masseter muscle in rats with or without occlusal interference. METHODS: Six-teen male Sprague-Dawley rats (220-250 g) were randomly divided into four groups: the naive control group, naive exercise group, occlusal interference control group, and occlusal interference exercise group. The rats in occlusal interference groups (occlusal interference control group and occlusal interference exercise group) obtained occlusal interference with 0.4 mm-thick crowns bonded to the right maxillary first molars. The rats in exercise groups (naive exercise group and occlusal interference exercise group) performed squat-type resistance exercises for 30 minutes, once a day, 5 days/week, lasting for 14 weeks. Resistance exercise was recorded every day. Mechanical withdrawal thresholds of bilateral masseter muscle were tested per week by use of modified electronic von-frey anesthesiometer. The rats were weighed per week. After the 14-week exercise, the muscle strength of the hindlimb was tested with a grip strength meter. Muscle (gastrocnemius and soleus) weight of bilateral hindlimb and length of bilateral fibula of the rats were obtained. The muscle-mass/body-mass ratios and muscle-mass/fibula-length ratios were calculated. RESULTS: Between the naive control group and naive exercise group, there was no significant difference in the mechanical withdrawal thresholds of bilateral masseter muscle for the 0-4 weeks (P>0.05). During the 5-14 weeks, the mechanical withdrawal thresholds of the rats in the naive exercise group were higher than those in the naive control group (P<0.05). Between the occlusal interference control group and occlusal interference exercise group, there was no significant difference in the mechanical withdrawal thresholds of bilateral masseter muscle for the 0-6 weeks (P>0.05). During the 7-14 weeks, the mechanical withdrawal thresholds of rats in the naive exercise group were higher than those in the occlusal interference control group (P<0.05). After the 14week exercise, the body mass of the rats in nonexercise group (the naive control group and occlusal interference control group) were larger than those in exercise group [(462±6) g vs. (418±14) g, P<0.05]. And the muscle strength of hindlimb of the rats in exercise group were bigger than those in non-exercise group [(6.75±0.13) N vs. (5.41±0.15) N, P<0.01]. CONCLUSION long-term resistance exercise can increase mechanical withdrawal thresholds of the bilateral masseter muscle in rats with or without masseter muscle mechanical hyperalgesia.
Animals ; Humans ; Hyperalgesia ; Male ; Masseter Muscle ; Molar ; Rats ; Rats, Sprague-Dawley ; Resistance Training

BACKGROUND: To date, there is no report on the successful construction of a three-dimensional finite element model of maxillary premolar with wedge-shaped defect restored by fiber post.OBJECTIVE: To establish the three-dimensional finite element model of maxillary premolar with wedge-shaped defect restored by fiber post. METHODS: Micro-CT was used to obtain imaging information of the human maxillary first premolar sample. Then Mimics, Geomagic and Hypermesh were used to establish a clear-structured three-dimensional finite element model of pulp-exposed maxillary premolar with wedge-shaped defect restored by fiber post. RESULTS AND CONCLUSION: The three-dimensional finite element model of normal maxillary premolar had 180 119 units and 33 289 nodes. Compared with the real subject, the three-dimensional finite element model of maxillary premolar with wedge-shaped defect restored by fiber post had vivid appearance, good image quality and accurate grid partitioning with 237 496 units and 43 965 nodes in total, which could obtain good results in the aspects of geometry, boundary constraint and mechanical compatibility. Moreover, it could better simulate the mechanical stress distribution of diseased teeth under occlusion to further confirm the magnitude and distribution of forces, thereby providing a better basis for future biomechanical studies.