Activation of GABAergic neurons in the zona incerta accelerates anesthesia induction with sevoflurane and propofol without affecting anesthesia maintenance or awakening in mice / 南方医科大学学报

OBJECTIVE@#To explore the regulatory effects of GABAergic neurons in the zona incerta (ZI) on sevoflurane and propofol anesthesia.@*METHODS@#Forty-eight male C57BL/6J mice divided into 8 groups (n=6) were used in this study. In the study of sevoflurane anesthesia, chemogenetic experiment was performed in 2 groups of mice with injection of either adeno-associated virus carrying hM3Dq (hM3Dq group) or a virus carrying only mCherry (mCherry group). The optogenetic experiment was performed in another two groups of mice injected with an adeno-associated virus carrying ChR2 (ChR2 group) or GFP only (GFP group). The same experiments were also performed in mice for studying propofol anesthesia. Chemogenetics or optogenetics were used to induce the activation of GABAergic neurons in the ZI, and their regulatory effects on anesthesia induction and arousal with sevoflurane and propofol were observed; EEG monitoring was used to observe the changes in sevoflurane anesthesia maintenance after activation of the GABAergic neurons.@*RESULTS@#In sevoflurane anesthesia, the induction time of anesthesia was significantly shorter in hM3Dq group than in mCherry group (P < 0.05), and also shorter in ChR2 group than in GFP group (P < 0.01), but no significant difference was found in the awakening time between the two groups in either chemogenetic or optogenetic tests. Similar results were observed in chemogenetic and optogenetic experiments with propofol (P < 0.05 or 0.01). Photogenetic activation of the GABAergic neurons in the ZI did not cause significant changes in EEG spectrum during sevoflurane anesthesia maintenance.@*CONCLUSION@#Activation of the GABAergic neurons in the ZI promotes anesthesia induction of sevoflurane and propofol but does not affect anesthesia maintenance or awakening.

Effect of processing method on chemical constituents of Rehmanniae Radix: based on UHPLC-LTQ-Orbitrap MS / 中国中药杂志

This study aims to explore the chemical composition of Rehmanniae Radix braised with mild fire and compare the effect of processing method on the chemical composition of Rehmanniae Radix. To be specific, ultra-high performance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to screen the chemical constituents of Rehmanniae Radix. The chemical constituents were identified based on the relative molecular weight and fragment ions, literature information, and Human Metabolome Database(HMDB). The ion peak area ratio of each component before and after processing was used as the index for the variation. SIMCA was employed to establish principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) models of different processed products. According to the PCA plot, OPLS-DA plot, and VIP value, the differential components before and after the processing were screened out. The changes of the content of differential components with the processing method were analyzed. A total of 66 chemical components were identified: 57 of raw Rehmanniae Radix, 55 of steamed Rehmanniae Radix, 55 of wine-stewed Rehmanniae Radix, 51 of repeatedly steamed and sundried Rehmanniae Radix Praeparata, 62 of traditional bran-braised Rehmanniae Radix, and 63 of electric pot-braised Rehmanniae Radix. Among them, the 9 flavonoids of braised Rehmanniae Radix were from Citri Reticulatae Pericarpium. PCA suggested significant differences in the chemical composition of Rehmanniae Radix Praeparata prepared with different processing methods. OPLS-DA screened out 32 chemical components with VIP value >1 as the main differential components. Among the differential components, 9 were unique to braised Rehmanniae Radix(traditional bran-braised, electric pot-braised) and the degradation rate of the rest in braised(traditional bran-braised, electric pot-braised) or repeatedly steamed and sundried Rehmanniae Radix was higher than that in the steamed or wine-stewed products. The results indicated the chemical species and component content of Rehmanniae Radix changed significantly after the processing. The 32 components, such as rehmapicrogenin, martynoside, jionoside D, aeginetic acid, hesperidin, and naringin, were the most important compounds to distinguish different processed products of Rehmanniae Radix. The flavonoids introduced by Citri Reticulatae Pericarpium as excipient may be the important material basis for the effectiveness of braised Rehmanniae Radix compared with other processed products.

Recent progress in delivery systems for photosensitizers and anti-cancer photodynamic therapy / 药学学报

Photodynamic therapy (PDT) is a new modality for cancer therapy, which has been used in the clinical treatment for various tumors, such as skin cancer, bladder cancer and prostate cancer. Most photosensitizers have the disadvantages of hydrophobic, low bioavailability and the limited tumor targeting ability. The nanoscale delivery systems can improve the solubility of photosensitizers and enhance their accumulation at the tumor sites. The multifunctional nano-delivery systems are prepared in combination with other anti-tumor drugs to enhance the anti-tumor effect. In addition to addressing the issues of poor solubility and the insufficient tumor targeting ability, the nanoscale delivery systems need to improve the pharmacokinetic properties of photosensitizers, facilitating their rapid accumulation at the tumor sites and quick elimination in vivo, and reducing the skin phototoxicity. This review summarizes the recent clinical application of PDT of cancer, the development of photosensitizers, the delivery systems for photosensitizers and the combinatorial application with other therapeutic methods. The goal is to present an understanding of knowledge on the design of new types of photosensitizers and its clinical application in PDT of cancer.

Effect of obesity induced by high-fat diet and adipose exosomes on knee post-traumatic osteoarthritis caused by destabilization of medial meniscus surgery in young mice / 药学学报

Obesity is an important risk factor related to osteoarthritis, but it′s role in post-traumatic osteoarthritis on young people need to further study. The internal mechanism except the mechanical loading may be associated with adipose exosomes. To examine the effect of obesity induced by high fat diet and adipose exosomes on knee post-traumatic osteoarthritis caused by destabilization of medial meniscus (DMM) surgery in young mice, 20 6-week-old C57BL/6J mice were randomly assigned to the control diet group (CD, n = 5), the DMM group (n = 5), the high fat diet group (HFD, n = 5) and the HFD plus DMM group (HFD+DMM, n = 5). The CD and DMM group were fed with a control diet, and the HFD and HFD+DMM group were fed with a high fat diet. We did the DMM surgery and the sham surgery on the mice when it was 10 weeks old. Extract obese and normal adipose exosomes, identify exosomes in vitro, and proceed fluorescence imaging in vivo using DiR staining. DMM+HFD-Exo group and DMM+CD-Exo group were injected the exosomes from the tail vain once a week (100 μL per shot with a concentration of 1 μg·μL-1). Second, 15 6-week-old C57BL/6J mice were randomly assigned to the DMM group (n = 5), the DMM plus obese adipose exosomes group (DMM+HFD-Exo, n = 5), and the DMM plus control diet adipose exosomes group (DMM+CD-Exo, n = 5). Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Nanjing University (IACUC-D2204005). All mice were sacrificed at the age of 18 weeks, the knee joints of the mice were harvested and fixed. We used micro CT to examine the samples and measured the bone volume/tissue volume, trabecular thickness, trabecular number and trabecular separation. Then the samples were decalcified and embedded in paraffin, and 4 μm thickness sections were stained with H&E and safranin O/fast green to observe the histological changes of the knee joint. The results showed compared with the control diet group, high fat diet induced obesity can aggravate the pathological changes of the post-traumatic osteoarthritis caused by DMM surgery, which shows in having a higher Mankin score. The surface of knee articular cartilage in the HFD+DMM group was rough, and the subchondral bone has an increase in bone sclerosis. Compared with the DMM group, obese adipose exosomes can exacerbate the pathological changes of the knee articular cartilage, while not influencing the subchondral bone. In conclusion, high fat diet induced obesity can aggravate the post-traumatic osteoarthritis caused by DMM surgery in young mice. The obese adipose exosomes mainly affect the surface of the knee articular cartilage.

Dopaminergic Neurons in the Ventral Tegmental-Prelimbic Pathway Promote the Emergence of Rats from Sevoflurane Anesthesia / 神经科学通报·英文版

Dopaminergic neurons in the ventral tegmental area (VTA) play an important role in cognition, emergence from anesthesia, reward, and aversion, and their projection to the cortex is a crucial part of the "bottom-up" ascending activating system. The prelimbic cortex (PrL) is one of the important projection regions of the VTA. However, the roles of dopaminergic neurons in the VTA and the VTADA-PrL pathway under sevoflurane anesthesia in rats remain unclear. In this study, we found that intraperitoneal injection and local microinjection of a dopamine D1 receptor agonist (Chloro-APB) into the PrL had an emergence-promoting effect on sevoflurane anesthesia in rats, while injection of a dopamine D1 receptor antagonist (SCH23390) deepened anesthesia. The results of chemogenetics combined with microinjection and optogenetics showed that activating the VTADA-PrL pathway prolonged the induction time and shortened the emergence time of anesthesia. These results demonstrate that the dopaminergic system in the VTA has an emergence-promoting effect and that the bottom-up VTADA-PrL pathway facilitates emergence from sevoflurane anesthesia.

Development and validation of a predictive model for the risk of 30-day death in emergency department patients / 中华危重病急救医学

Objective:To explore the risk factors for 30-day death in emergency department patients, and then construct a prediction model and validate it using nomogram.Methods:A retrospective cohort study was conducted. The clinical data of 1 091 patients admitted to the emergency department of the First People's Hospital of Changde from January 1 to June 30, 2021 was collected, including 741 patients from January 1 to March 31 in the development group and 350 patients from April 1 to June 30 in the validation group. General information, first vital signs admitted to the emergency department, and laboratory results were collected, the modified early warning score (MEWS) was calculated, and 30-day outcomes were recorded. Univariate and multivariate Logistic regression analysis was used to screen out the risk factors of 30-day death. According to the results of multivariate analysis, the nomogram was used to construct a 30-day death prediction model. The receiver operator characteristic curve (ROC curve) was used to evaluate the consistency of the prediction model, the calibration of the prediction model was evaluated by the Hosmer-Lemeshow goodness of fit test.Results:A total of 1 091 patients were enrolled. There were 741 patients in the development group, including 356 males and 385 females, aged (51.42±17.33) years old, and the 30-day mortality was 28.88%. There were 350 patients in the validation group, including 188 males and 162 females, aged (52.88±16.11) years old, and the 30-day mortality was 24.00%. The results of the univariate analysis showed that age, primary diagnosis on admission, consciousness, respiratory rate (RR), systolic blood pressure (SBP), heart rate (HR), pulse oxygen saturation (SpO 2), MEWS score, erythrocyte sedimentation rate (ESR), procalcitonin (PCT) and body mass index (BMI) might be the risk factors for 30-day death in patients in the emergency department. The results of the multivariate analysis showed that the MEWS score [odds ratio ( OR) = 14.22, 95% confidence interval (95% CI) was 1.46-138.12], ESR ( OR = 46.71, 95% CI was 20.48-106.53), PCT ( OR = 4.97, 95% CI was 2.46-10.02), BMI (24.0-27.9 kg/m 2: OR = 37.82, 95% CI was 14.69-97.36; ≥28.0 kg/m 2: OR = 62.11, 95% CI was 25.77-149.72) were independent risk factors for 30-day death in the emergency department (all P < 0.05). Using the four variables with the results of multivariate analysis to construct a nomogram prediction model, the area under the ROC curve (AUC) was 0.974 (95% CI was 0.753-0.983) for the development group, and the AUC was 0.963 (95% CI was 0.740-0.975) for the validation group. The Hosmer-Lemeshow test showed no statistically significant difference between the predicted outcome of the nomogram prediction model and the actual occurrence ( χ2 = 1.216, P = 1.270). Conclusion:The prediction model developed by the MEWS score combined with BMI, ESR and PCT can scientifically and effectively predict the 30-day outcome of emergency department patients.

Neonatal mortality analysis of Chifeng city / 中国新生儿科杂志

Objective:To study the current neonatal mortality rate and causes of deaths in Chifeng city to further reduce neonatal mortality.Methods:From 2018 to 2019, neonatal mortality data of Chifeng, Inner Mongolia were reviewed. Neonatal mortality, causes of deaths, the distribution of mortality in different groups of neonates and different tiers of hospitals were analyzed.Results:A total of 172 neonatal deaths were included. The top five causes of deaths were asphyxia (23.8%), respiratory distress syndrome (RDS) (22.7%), severe congenital malformation (18.0%), infection (11.6%) and preterm birth (9.3%). Among the 172 neonates, 61 were full-term (35.5%). The leading causes of deaths were asphyxia (34.4%), severe congenital malformation (32.8%) and RDS (13.1%). 111 were premature infants (64.5%), including 16 infants (14.4%) with gestational age (GA)≤30 weeks died without treatment. The leading causes of deaths in premature infants receiving treatment were RDS (29.7%), asphyxia (18.0%) and infection (15.3%). 124 cases (74.0%) were early neonatal death (END) (death within 7 d after birth). The top 3 causes of END in preterm infants were RDS (43.1%), asphyxia (27.7%) and severe congenital malformations (12.3%). The top 3 causes of END in full-term infants were asphyxia (44.2%), severe congenital malformations (23.3%) and RDS (18.6%). 48 cases (26.0%) were late neonatal death (LND) (death after 7 d of age). The top 3 causes of LDN in preterm infants were infection (33.3%), RDS (10.0%) and severe congenital malformations (10.0%).The top 3 causes of LND in full-term infants were severe congenital malformations (55.6%), asphyxia (11.1%) and genetic diseases (11.1%). Compared with Tier II hospitals, the GA [(33.1±4.2) weeks vs. (35.0±5.1) weeks] and the birth weight (BW) [(2 000±480) g vs. (2 620±515) g] were lower in Tier Ⅲ hospitals ( P<0.05). For full-term infants, the proportion of asphyxia as the cause of deaths in Tier Ⅱ hospitals was significantly higher than Tier Ⅱ hospitals ( P<0.05). Conclusions:Neonatal deaths mainly occur within the first week after birth with asphyxia, prematurity, severe congenital malformations, infection and RDS as the leading causes. The causes of deaths of preterm and full-term infants are different at different postnatal ages. For full-term infants, the incidences of deaths due to asphyxia are higher in Tier Ⅱ hospitals than Tier Ⅲ hospitals.

PAK6: a potential anti-cancer target

p21-activated kinase 6 (PAK6) is a member of the PAK family of serine/threonine kinases that are known effectors of Rho GTPases Cdc42 and Rac. PAKs regulate a large number of complex cellular mechanisms, including cell motility, morphology, and tumor development. PAK6, initially cloned as an interacting partner of the androgen receptor (AR), is associated with an array of cellular processes implicated in tumor progression. However, the full biological implications of PAK6 activity during cancer remain poorly understood. In this review, we assess our current understanding of the physiological roles of classical PAK6 functionality in mammals, in addition to its emerging role in tumorigenesis.

Effect of Yinfupian and Yangfupian on Brown Adipose Tissue of Yang Deficiency Mice / 中国实验方剂学杂志

Objective:To observe the expression of brown adipose tissue (BAT), cells, proteins and corresponding genes in Yang deficiency model mice induced by Rhei Radix et Rhizoma suspension, and to explore the thermogenesis of processed products of Aconiti Lateralis Radix Praeparata with Jianchang faction characteristics. Method:Twenty mice, half male and half female, were randomly selected as the normal female and male groups. And the other 80 mice were administrated with Rhei Radix et Rhizoma suspension (the content of 0.25 g·mL-1) to establish Yang deficiency model, after the model was established, they were randomly divided into the model female and male groups, female and male groups of Shengfupian, female and male groups of Yinfupian, female and male groups of Yangfupian, 10 mice in each group. Mice were intragastric administrated with corresponding medical solution for two weeks (1.54 g·kg-1·d-1) according to groups. Normal group and model group were given equal volume distilled water. After administration, BAT of scapular region of mice was collected and the changes of BAT cells were observed by hematoxylin-eosin (HE) staining. The expression of uncoupling protein 1 (UCP1) and its mRNA were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Result:Compared with the normal group of the same sex, the proportion of BAT in the model group decreased significantly (P<0.01). Compared with the model group of the same sex, the proportion of BAT in female mice from Shengfupian and Yinfupian groups increased significantly (P<0.01), while there was no significant difference between each administration group and model group in the male mice. Compared with normal mice of the same sex, there were many scattered vacuoles in BAT cells of the model group, and fewer cells could be observed due to larger vacuoles. Compared with the model group of the same sex, BAT cells in mice from the Shengfupian group showed fewer vacuoles, smaller cells and tight arrangement, the density of BAT cells in mice from the Yangfupian group also increased significantly, while the vacuoles in BAT cells of mice from the Yinfupian group decreased relatively and the cells did not increase significantly. Compared with the same sex mice, the expression level of UCP1 in the model group and the normal group was statistically significant (P<0.05, P<0.01). In the female mice, the expression level of UCP1 in Yangfupian group was significantly higher than that in the model group (P<0.05), each administration group of male mice was significantly different from that of the model group of the same sex (P<0.05), of which Yangfupian was the most significant. The relative expression of UCP1 mRNA in the model group was significantly lower than that in the normal group of the same sex (P<0.05, P<0.01). In the female mice, compared with the model group, the relative expression levels of UCP1 mRNA in Yangfupian group, Shengfupian group and Yinfupian group increased significantly (P<0.05, P<0.01), compared with Yangfupian group, the relative expression levels of UCP1 mRNA in Shengfupian and Yinfupian were also significantly different (P<0.05). In the male mice, compared with the model group, the relative expression of UCP1 mRNA in Yangfupian group was significantly increased (P<0.01), but there was no significant difference in Shengfupian group and Yinfupian group, in addition, compared with Yangfupian group, the relative expression of UCP1 mRNA in Shengfupian group and Yinfupian group had significant difference (P<0.05). Conclusion:Shengfupian, Yinfupian and Yangfupian all have obvious improvement on Yang deficiency syndrome induced by Rhei Radix et Rhizoma suspension. The mechanism may be to promote the expression of UCP1 protein and its mRNA and enhance the activity of BAT. And the effect of Yangfupian is the best.

Moxibustion relieves abdominal hypersensitivity and diarrhea by regulating colonic 5-hydroxytryptamine signaling pathway in rats with diarrhea type irritable bowel syndrome / 针刺研究

OBJECTIVE: To observe the effect of moxibustion on visceral pain, diarrhea, colonic 5-hydroxytryptamine (5-HT) content, and expression of tryptophan hydroxylase 1 (TPH1), serotonin reup take transporter (SERT) and 5-hydroxytryptamine receptor 3 (5-HT3R) in colon tissue of rats with diarrhea irritable bowel syndrome (IBS-D), so as to reveal its underlying mechanisms in treating IBS-D. METHODS: Thirty male SD rats were randomly divided into blank control, model and moxibustion groups (n＝10 rats in each group). The IBS-D model was established by chronic restraint combined with gavage of Senna leaf solution. Moxibustion was applied to bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37) for 30 min, once a day for 7 days. After the treatment, the loose stool rate (number of loose stool/total number of feces granules X100%) and the minimum volume threshold of abdominal reflex (abdominal pain threshold) induced by rectal dilatation were observed. The content of colonic 5-HT was detected by using ELISA, and the expression of TPH1, SERT and 5-HT3R mRNAs and proteins were detected by using quantitative real time-PCR and Western blot, respectively. RESULTS: Compared with the blank control group, the minimum volume threshold of abdominal retraction reflex and the relative expression of SERT protein and mRNA were significantly decreased (P<0.01), and the loose stool rate, colonic 5-HT content, and relative expression of TPH1 and 5-HT3R proteins and mRNAs were notably increased in the model group (P<0.01). After moxibustion, both the decrease of minimum volume threshold and SERT protein and mRNA expressions and the increase of loose stool rate, colonic 5-HT content and TPH1 and 5-HT3R protein and mRNA expressions were reversed (P<0.01). CONCLUSION: Moxibustion of ST25 and ST37 can relieve abdominal hypersensitivity and diarrhea in IBS-D model rats, which is related to its effects in down-regulating colonic 5-HT content and expression of TPH1 and 5-HT3R proteins and mRNAs and in up-regulating expression of SERT protein and mRNA (regulating 5-HT/5-HT3R signaling)．.

Historical Evolution and Modern Research Progress of Processed Products of Aurantii Fructus / 中国实验方剂学杂志

The processing of Aurantii Fructus has a long history and many methods. In addition to the current mainstream varieties of raw products and stir-fried products with bran of Aurantii Fructus, other 17 processing methods, such as stir-fried with rice, processed with salt, honey and medicinal juice, are recorded in the literature of past dynasties. Through a comprehensive review and sorting out of ancient and modern literature, this paper clarifies the historical evolution of the processing of Aurantii Fructus, through clarifying the historical evolution of processing and analyzing the present situation of modern research on Aurantii Fructus, summarizes the modern research progress on processing in production place, processing technology, chemical compositions and pharmacological effects before and after being processed, and puts forward some ideas for the follow-up research on processing of Aurantii Fructus, in order to provide reference for screening the dominant varieties, standardizing the processing technology, explaining the scientific connotation of processing, and improving the utilization ratio of medicinal resources of Aurantii Fructus.

Treatment of recurrent café-au-lait spots with Q532 laser: a clinical study / 中华医学美学美容杂志

Objective To explore the clinical efficacy and side effects of Q 532 laser in the treatment of recurrent café-au-lait spots.Methods Collection period was from January 2018 to January 2019.Fifty-five patients with recurrent café-au-lait spots after 2-3 times of Q-switched 755 laser treatment were selected and then treated with Q-switched 532 laser.Treatment was given once every 3-6 months.The appropriate treatment parameters were selected according to the patient's condition.The effects of age,gender,size,morphology and margin of the lesion on the treatment were observed.Results Among the 55 patients treated with Q 532 laser after 2 to 5 treatments,19 cases were cured,13 cases markedly effective,15 cases moderately effective,8 cases invalid with a total effective rate of 85 ％.Conclusions Q 532 laser is an effective and safe treatment for recurrent Café-au-lait spots.

Efficacy of sevoflurane in preventing depression-like behavior in mice: the relationship with BDNF/TrkB signaling pathway / 中华麻醉学杂志

Objective To evaluate the efficacy of sevoflurane in preventing depression-like behavior in mice and the relationship with brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling pathway.Methods Forty-four clean-grade male C57BL/6 mice,weighing 18-22 g,aged 8-10 weeks,were divided into 2 groups (n =22 each) using a random number table method:control group (group C) and sevoflurane group (group S).Mice in group C inhaled oxygen for 30 min,and mice in group S inhaled 2.5％ sevoflurane for 30 min.The forced swimming test and novelty-suppressed feeding test were performed after the mice were fully awake.The brains were immediately removed under anesthesia at the end of inhalation of oxygen or sevoflurane,and the prefrontal cortex and hippocampus were isolated for detection of the expression of BDNF,TrkB and phosphorylated TrkB (p-TrkB) by Western blot.Results Compared to group C,the immobility time and feeding latency were significantly shortened,the expression of p-TrkB in the prefrontal cortex and hippocampus was up-regulated (P＜0.05),and no significant change was found in the feeding consumption or expression of BDNF and TrkB in the prefrontal cortex and hippocampus in group S (P＞0.05).Conclusion Sevoflurane produces a preventive effect on depression-like behavior in mice,and the mechanism is related to increased phosphorylation of TrkB in BDNF/TrkB signaling pathway.

Research progress of mast cells in the mechanism of intestinal injury caused by deep hypothermic circulatory arrest / 中国胸心血管外科临床杂志

@#Deep hypothermic circulatory arrest (DHCA) is an important assistant technique for complex cardiac surgery, which creates convenient operating conditions for surgery, and is also one of the measures to protect the brain during operation. However, the complications caused by this technique cannot be ignored, and it should be noticed that the occurrence of intestinal injury is relatively insidious, but brings great pain to patients and significantly reduces the quality of life after operation. Studies have shown that intestinal ischemia-reperfusion injury is induced by DHCA. It causes mast cells to activate and release many inflammatory mediators that destroy the intestinal mucosal epithelium barrier, and eventually lead to intestinal injury. This article reviewed the research progress of mast cells in the mechanism of DHCA-induced intestinal injury.

Effect and molecular mechanism of isorhamnetin extracted from Ginkgo biloba on the differentiation of RAW264.7 cells into osteoclasts / 口腔疾病防治

Objective @#To investigate the effect and potential molecular mechanisms of isorhamnetin (ISO) extracted from Ginkgo biloba on the differentiation of osteoclasts.@*Methods@#Osteoclast precursor RAW264.7 cells were induced with RANKL to differentiate into mature osteoclasts. Different concentrations of ISO were added to RAW264.7 cells to determine its effect on osteoclast differentiation. CCK8 was used to evaluate the effect of ISO on cytotoxicity. The impact of ISO on the osteoclast differentiation process was investigated by analyzing tartrate resistance and bone resorption lacuna. Real-time PCR was performed to analyze the levels of differentiation marker genes, including tartrate resistant acid phosphatase (Trap), cathepsin K (Ctsk), and matrix metalloproteinase 9 (MMP-9); differentiation-related transcription factors, including the proto-oncogene protein c-Fos, nuclear factor of activated T-cells cytoplasmic 1(NFATc1); and the levels of downstream NF-κB p65 signaling pathway phosphorylation. Using the above-described method, we verified that ISO exerted an inhibitory effect on osteoclast differentiation and explored related molecular mechanisms. @*Results @#Different concentrations of ISO (1-10 μM) had no cytotoxic effects on RAW264.7 cells, inhibited TRAP activity and decreased the number of bone resorption lacuna during osteoclast differentiation. When applied at a concentration of 10 μM, its inhibitory effect was significant. In addition, ISO significantly reduced the expression levels of Trap, Ctsk, MMP-9, c-Fos, NFATc1 and NF-κB p65 mRNA. @*Conclusion@# ISO extracted from Ginkgo biloba extract exerted an inhibitory effect on osteoclast differentiation, and the mechanism underlying its activity may involve the inhibition of the classical NF-κB pathway.

Sequential method for determining the maximum dose of mivacurium continuously infused for intraoperative neuromonitoring in thyroid surgery / 南方医科大学学报

OBJECTIVE@#To determine the maximum dose of continuously infused mivacurium for intraoperative neuromonitoring and observe its adverse effects in thyroid surgery.@*METHODS@#Twenty-eight patients undergoing thyroid surgery with intraoperative neuromonitoring received continuous infusion of mivacurium at the initial rate of 5.43 μg?kg?min, and the infusion rate for the next patient was adjusted based on the response of the previous patient according to the results of neurological monitoring. The depth of anesthesia was maintained with sevoflurane and remifentanil during the surgery. The LD50 and 95% of mivacurium were calculated using Brownlee's up-and-down sequential method.@*RESULTS@#The LD50 of continuously infused mivacurium was 8.94 μg?kg?min (95% : 8.89- 8.99 μg?kg?min) during thyroid surgery, which did not affect neurological function monitoring. Transient chest skin redness occurred after induction in 9 patients (32.1%). None of the patients experienced intubation difficulties or showed intraoperative body motions during the surgery.@*CONCLUSIONS@#In patients undergoing thyroid surgery under anesthesia maintained by inhalation and intravenous infusion, the LD50 of mivacurium was 8.94 μg?kg?min (95% : 8.89-8.99 μg?kg?min) for continuous infusion, which does not cause serious adverse effects during the operation.

Expression of phosphoglycerate kinase 1 in endometrial carcinoma and its association with patients' outcome / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of phosphoglycerate kinase 1 (PGK1) and its prognostic value in endometrial carcinoma (EC).</p><p><b>METHODS</b>The expression of PGK1 was detected immunohistochemically in 30 normal endometrium and 130 EC specimens. The relationship between PGK1 protein expression and the clinicopathological features of the patients was evaluated.</p><p><b>RESULTS</b>Immunohistochemical analysis revealed low PGK1 expression in 55.4% (72/130) and high PGK1 expression in 44.6% (58/130) of the EC specimens, as compared with the rates of 90% (27/30) and 10% (3/30) in normal endometrium, respectively (P<0.001). PGK1 expression was significantly correlated with FIGO stage (P<0.001), histological grade (P=0.002) and lymph node metastasis (P<0.001). Kaplan-Meier survival analysis indicated that patients with a high PGK1 expression had a shorter overall survival rate than those with a low PGK1 expression (P<0.001). Multivariate analysis showed that a high PGK1 expression was not the independent predictor of the prognosis of EC (P=0.077).</p><p><b>CONCLUSION</b>A high expression of PGK1 is associated with aggressive and metastatic behaviors of EC, and detection of PGK1 provides assistance in evaluating the prognosis of patients with EC.</p>

Clinicial efficacy and prognosis of bevacizumab combined with chemotherapy in retreated advanced non-squamous non-small cell lung cancer / 中国肿瘤临床

Objective:To investigate the efficacy and safety of bevacizumab combined with chemotherapy in patients with retreated advanced non-squamous non-small cell lung cancer (NSNSCLC) and analyze its prognostic factors. Methods:Forty-one patients with previously treated advanced NSNSCLC in Beijing Chest Hospital from February 2013 to June 2017 were recruited. Clinical data of the patients were retrospectively analyzed. There were 38 cases of adenocarcinoma and 3 cases of other pathological types. Bevacizumab combined with chemotherapy served as second-line treatment for 19 patients, and it served as beyond second-line therapy for 22 pa-tients. Eighteen patients harbored epidermal growth factor receptor (EGFR) gene mutations, while the other 23 patients harbored wild-type EGFR gene. The efficacy and safety of bevacizumab combined with chemotherapy were evaluated. To evaluate the prognos-tic factors, single and multiple factor analyses were conducted. Results:All patients received bevacizumab combined with chemothera-py and could be evaluated for response. The mean number of cycles of chemotherapy and chemotherapy combined with bevacizumab were 3.1 and 5.0, respectively. The objective response rate (ORR) of all recruited patients was 12.2％. The disease control rate (DCR) was 82.9％. Regarding the effect of second-line and beyond second-line therapy in patients, data were similar. The ORRs were 10.5％and 13.6％, respectively (P=0.572), and DCRs were 89.5％and 77.3％, respectively, without significantly statistical difference (P=0.271). The median progression-free survival (PFS) and overall survival (OS) were 4.6 months [95％confidence interval (CI) 3.619-5.581] and 11.9 months (95％CI 9.797-14.003), respectively. In the single factor analysis, patients with EGFR mutations, those who received>4 cy-cles of bevacizumab administration, and women had longer OS (χ2=19.673, P=0.000;χ2=6.820, P=0.009;andχ2=6.374, P=0.012;respec-tively). The Cox regression analysis showed that EGFR mutation status and number of cycles of bevacizumab administration were inde-pendent prognostic factors [hazard ratio (HR)=0.129, P=0.001 and HR=0.336, P=0.012;respectively]. The common adverse reactions in-clude bone marrow suppression, bleeding, hypertension, and proteinuria. Most of them were grade 1-2. Conclusions:Bevacizumab combined with chemotherapy provides good efficacy and controllable safety in patients with retreated advanced NSNSCLC. Patients with EGFR mutations and>4 cycles of bevacizumab administration have superior prognosis.

Etiology and clinical features of drug-induced liver injury diagnosed by liver biopsy / 解放军医学杂志

Objective To investigate the etiology and clinical features of drug-induced liver injury (DILI).Methods A total of 194 DILI in patients,who underwent liver biopsy in our hospital from January 2015 to December 2015,were enrolled in the study.The etiology,laboratory markers (such as alanine transaminase,aspartate aminotransferase,total bilirubin,gammaglutamyl transferase and alkaline phosphatase),and the pathological features were analyzed retrospectively.Then,all of the patients were followed up every 3 or 6 months,with a mean of 34.5 months.The risk factors associated with relapse,which was defined as liver enzymes (such as ALT or TBIL) rising at least 2 times of its upper limit of normal value (ULN),were analyzed with a logistic regression model.Results In terms of etiology,Traditional Chinese medicine (TCM) was the most common cause of DILI,which accounted for 46.9％ of patients,in return followed by acetaminophen-containing drugs (14.4％),antibiotics (9.3％),environmental toxins (4.6％),antidepressant (4.6％),dietary supplement (3.1％),lipid-lowering drugs (3.1％),chemotherapeutic agents (2.6％,and others unknown (11.3％).Of 194 DILI patients,hepatocellular type was observed in 78(40.2％) patients,cholestatic type in 63(32.5％),and mixed type in 53(27.3％).Histological findings showed that 70(36.1％) patients had an acute injury,124(63.9％) chronic damages,which composed by G0(9.8％),G,(19.1％),G2(21.6％),G3(9.8％),and G4(3.6％) in terms of inflammation level.Twenty-seven cases (21.8％) relapsed after discharge from hospital,multivariate analysis showed that cholinesterase is an independent risk factor which might predict the relapse of DILI patients.Conclusions The incidence of DILI is increasing,especially induced by TCM,therefore clinicians should master the clinical features of the disease in order to achieve correct diagnosis and establish the optimal treatment strategy.

Primary culture and identification of cells from human aldosterone-producing adenoma / 基础医学与临床

Objective To establish the primary culture of aldosterone-producing adenoma cells. Methods The tumor tissue was digested by collagen type I and cultured in complete DMEM/F12 medium. Aldosterone concentra-tion in culture medium was detected by radioimmunoassay. The expression of aldosterone synthase in the culture cells was detected by immunofluorescence. Results Aldosterone-producing adenoma cells grew adherently in a round or approximately round shape. The cells were positively immunostained for aldosterone synthase. The aldoste-rone concentration in the culture medium at the 5th culture day was (30.0±8.9)nmol/L. During the primary cul-ture,aldosterone secretion was the strongest at the first day,and decreased afterwards. It kept stable from day 4 to 11. Conclusions We successfully established the primary culture of aldosterone-producing adenoma cells, which are important for the future studying on the mechanism and function of aldosterone-producing adenoma.