Comparison of mouse models of depression induced by different modeling methods / 生理学报

The present article was aimed to compare the effectiveness of different induction methods for depression models. Kunming mice were randomly divided into chronic unpredictable mild stress (CUMS) group, corticosterone (CORT) group, and CUMS+CORT (CC) group. The CUMS group received CUMS stimulation for 4 weeks, and the CORT group received subcutaneous injection of 20 mg/kg CORT into the groin every day for 3 weeks. The CC group received both CUMS stimulation and CORT administration. Each group was assigned a control group. After modeling, forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to detect the behavioral changes of mice, and the serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT) and CORT were detected with ELISA kits. Attenuated total refraction (ATR) spectra of mouse serum were collected and analyzed. HE staining was used to detect morphological changes in mouse brain tissue. The results showed that the weight of model mice from the CUMS and CC groups decreased significantly. There was no significant change in immobility time of model mice from the three groups in FST and TST, while the glucose preference of model mice from the CUMS and CC groups was significantly reduced (P < 0.05). The serum 5-HT levels of model mice from the CORT and CC groups were significantly reduced, while the serum BDNF and CORT levels of model mice from the CUMS, CORT, and CC groups showed no significant changes. Compared with their respective control groups, the three groups showed no significant difference in the one-dimensional spectrum of serum ATR. The difference spectrum analysis results of the first derivative of the spectrogram showed that the CORT group had the greatest difference from its respective control group, followed by the CUMS group. The structures of hippocampus in the model mice from the three groups were all destroyed. These results suggest that both CORT and CC treatments can successfully construct a depression model, and the CORT model is more effective than the CC model. Therefore, CORT induction can be used to establish a depression model in Kunming mice.

Effect of different administration methods of methoxamine on body temperature of patients undergoing off-pump coronary artery bypass grafting / 中国医师进修杂志

Objective:To observe the different administration methods of methoxamine on the body temperature protection of patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods:The clinical data of 278 patients underwent OPCABG from January 2019 to December 2021 in Jinzhou Central Hospital were retrospectively analyzed, and the patients were used the methoxamine during the operation. Among them, 157 cases were given methoxamine by continuous intravenous infusion (continuous intravenous infusion group), and 121 cases were given methoxamine by fractional intravenous infusion in stages (fractional intravenous infusion group). The changes of mean arterial pressure (MAP) and heart rate during operation were recorded, and the fluctuation rate of MAP was calculated. The dosage of methoxamine, use time of variable temperature blanket, time from the end of operation to waking up and occurrence of adverse reactions such as hypothermia, rigors, coagulation disorders and renal insufficiency were recorded.Results:During anesthesia, the fluctuation rate of MAP in continuous intravenous infusion group was significantly lower than that in fractional intravenous infusion group: (16.62 ± 3.17)% vs. (23.53±3.69)%, and there was statistical difference ( P<0.05). The MAP and heart rate of continuous intravenous infusion group were more stable at each time point than that of fractional intravenous infusion group. The use time of variable temperature blanket, and incidences of hypothermia, rigors in continuous intravenous infusion group were significantly lower than those in fractional intravenous infusion group: (86.17 ± 19.66) min vs. (146.72 ± 29.37) min, 2.55% (4/157) vs. 9.92% (12/121) and 1.91% (3/157) vs. 8.26% (10/121), and there was statistical difference ( P<0.01 or <0.05); there were no statistical differences in dosage of methoxamine, time from the end of operation to waking up and incidence of coagulation disorders between two groups ( P>0.05); Renal insufficiency did not occur in both groups. Conclusions:Continuous intravenous pumping of methoxamine can obviously reduce the heat loss of human body, enhance the insulation effect of other insulation measures, and reduce the incidence of hypothermia in patients underwent OPCABG.

Optimization of large-scale production process for human prothrombin complex concentrates / 中国输血杂志

【Objective】 To determine the optimal process conditions for efficiently extracting human prothrombin complex concentrates from human plasma. 【Methods】 Using human plasma as the materials and the yield of prothrombin complex concentrates as the evaluation standard, the preparation process parameters were studied and optimized through design of exporement(DOE), orthogonal experiments, and single factor experiments. 【Results】 The optimal process conditions were as follows: DEAE Sephadex A50 gel was selected, which balanced to pH 7.6, and then the amount of 1.7-2.5 g/L of plasma weight is added into the cryoprecipitate supernatant for adsorption for 40 minutes; Washing solution (0.15-0.175 mol/L sodium chloride) with 3 times the volume of gel was washed 3 times, and eluent (0.5-2.0 mol/L sodium chloride) was washed 3 to 5 times; Add stabilizer (heparin 35 IU, sodium chloride 0.1 mol/L) for ultrafiltration dialysis. 【Conclusion】 By using the optimized process mentioned above, the yield(measured by human coagulation factor IX)can reach 620 000 to 630 000 IU/ton of plasma, which is suitable for large-scale production.

Clinical characteristics and prognosis of posterior reversible encephalopathy syndrome with spinal cord involvement / 中华神经科杂志

Objective:To investigate the clinical manifestations, imaging features and prognosis of posterior reversible encephalopathy syndrome with spinal cord involvement (PRES-SCI).Methods:The clinical data of 1 patient with PRES-SCI admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University in November 2021 were analyzed, and the data of 38 patients with PRES-SCI reported in domestic and foreign databases and this patient were collected for pooled analysis.Results:The main clinical manifestations of 39 PRES-SCI patients (including this patient) included headache (79.5%, 31/39), visual disturbance (79.5%, 31/39), vomiting (46.2%, 18/39), disturbance of consciousness (38.5%, 15/39), limb weakness (28.2%, 11/39) and seizure (23.1%, 9/39). There were up to 97.4% (38/39) of patients who had significantly elevated blood pressure. The imaging feature was long-segment spinal cord lesion involving central gray matter. Approximately 89.7% (35/39) of the spinal cord lesions originated from the junction of the medulla oblongata and the cervical spinal cord. The median number of abnormal spinal cord segments corresponding to the vertebral body was 9 (the shortest was 4 and the longest was the entire spinal cord). Thirty-eight patients had brain lesions, and the most frequently involved sites were medulla oblongata (82.1%, 32/39), occipital lobe (46.2%, 18/39), pons (43.6%, 17/39), parietal lobe (41.0%, 16/39), and cerebellum (38.5%, 15/39). Among 38 patients completing the follow-up, 31 patients (81.6%) were clinically recovered.Conclusions:Posterior reversible encephalopathy syndrome could involve the spinal cord. For patients with long-segment spinal cord lesions and significantly increased blood pressure or other risk factors, PRES-SCI should be considered. Timely identification and treatment could make most patients recovery.

A multiomics comparative study on the intervention of fecal microbiota transplants of Fengshining on rheumatoid arthritis / 药学学报

The study aims to investigate the mechanism of Fengshining fecal microbiota transplants in the intervention of rheumatoid arthritis by ultra-performance liquid chromatography-quadrupole/electrostatic field obitrap high-resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). All animal welfare and experimental procedures followed the regulations of the Medical Ethics Committee of Shanxi University of Chinese medicine. The rats were randomly divided into normal group, model group, fecal microbiota transplantation group and Tripterygium wilfordii polyglycoside group, and the collagen induced arthritis (CIA) was established. The changes of body weight and metatarpodal lesions of rats were evaluated. The serum of rats in each group was analyzed by liquid chromatography-mass spectrometry and metagenomic technology for differential metabolites and microflora. The protein expression levels of Toll-like receptors (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor of kappa B (NF-κB p65) were detected by Western blot. A total of 13 different metabolites, including arachidonic acid, docosahexaenoic acid, 13S-hydroxyoctadecanodienoic acid and L-phenylalanine were screened from serum. Three metabolic pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and arachidonic acid metabolism were identified through pathway enrichment. Metagenomic analysis showed that the abundance of g_Bacteroides, g_Prevotella and p_Actinobacteria in CIA group was higher. The abundance of c_Clostridia, g_Akkermansia and s_Akkermansia_muciniphila in fecal microbiota transplantation group is higher. The hierarchical cluster heat map showed that Akkermansia was negatively correlated with L-phenylalanine; while positively correlated with docosahexaenoic acid. Prevotella was positively correlated with L-phenylalanine. Fecal microbiota transplantation group could significantly inhibit the expression of TLR4, MyD88 and p65 proteins in the synovium of rats (P < 0.01). The anti-rheumatoid arthritis effects of fecal microbiota transplantation group is closely related to the intervention of the metabolism of phenylalanine and arachidonic acid, through Akkermansia, Prevotella and other microorganisms, inhibition the TLR4/MyD88/NF-κB pathway.

Prevalence and trends of anemia among pregnant women in eight provinces of China from 2016 to 2020 / 中华预防医学杂志

This study analyzed the anemia status and change trend of 219 835 pregnant women in eight provinces from 2016 to 2020 in the Maternal and Newborn Health Monitoring Program(MNHMP). The results showed that from 2016 to 2020, the anemia rate of pregnant women in eight provinces was 41.27%, and the rates of mild, moderate and severe anemia were 28.56%, 12.59% and 0.12% respectively; the anemia rates in eastern, central and western regions were 41.87%, 36.09% and 44.63% respectively, and the anemia rates in urban and rural areas were 39.87% and 42.23%. From 2016 to 2020, the anemia rate of pregnant women decreased from 44.93% to 38.22%, with an average annual decline of 3.86% (95%CI:-5.84%, -1.85%). The anemia rate among pregnant women of the eastern region (AAPC=-6.16%, 95%CI:-9.79%, -2.38%) fell faster than that among pregnant women of the central region (AAPC=0.71%, 95%CI:-6.59%, 8.57%) and western region (AAPC=-1.53%, 95%CI:-5.19%, 2.28%). From 2016 to 2020, the moderate anemia rate in pregnant women decreased from 14.98% to 10.74%, with an average annual decline of 8.72% (95%CI:-12.90%, -4.34%), with a statistically significant difference (P<0.05); AAPC for mild and severe anemia in pregnant women was 1.56% (95%CI: 3.44%, 0.36%) and 18.86% (95%CI: 39.88%, 9.52%), respectively, without statistically significant difference (P>0.05).

New outlook on safety of traditional Chinese medicine: concept and practice / 中国中药杂志

Profound changes have taken place in human disease spectrum, constitution spectrum, and drug use behavior, and the safety of traditional Chinese medicine(TCM) faces new trends and problems. In particular, serious adverse reactions/events such as liver injury and kidney injury caused by non-toxic TCM have been frequently reported, overturning people's understanding of TCM safety, and even shaking the public's confidence in the development of TCM. In the new era of globalization, correctly understanding the situation and problems of TCM safety and addressing the dilemmas in safety evaluation and risk prevention of TCM are the key missions to be undertaken by TCM practitioners. This paper suggests that the situation and problems of TCM safety should be viewed objectively and dialectically, and the use standard of TCM should be advanced with the times. Furthermore, this paper puts forward the new conception and methodology of TCM safety(including one innovative understanding, two types of evaluation modes, tri-elements injury hypothesis; four-quadrant risk decision processes, and five-grade safety evidence body) for the first time, hoping to provide new theories, new strategies, new methods and successful examples for solving the safety problems of TCM.

Interpretation on Consensus on drug-induced liver injury by CIOMS Working Group:liver injury attributed to herbal and dietary supplements / 中国中药杂志

With the increase in the medical level, the improvement of adverse drug reaction(ADR) monitoring systems, and the enhancement of public awareness of safe medication, drug safety incidents have been frequently reported. Drug-induced liver injury(DILI), especially liver injury attributed to herbal and dietary supplements(HDS), has globally attracted high attention, bringing great threats and severe challenges to the people for drug safety management such as clinical medication and medical supervision. Consensus on drug-induced liver injury had been published by the Council for International Organizations of Medical Sciences(CIOMS) in 2020. In this consensus, liver injury attributed to HDS was included in a special chapter for the first time. The hot topics, including the definition of HDS-induced liver injury, epidemiological history, potential risk factors, collection of related risk signals, causality assessment, risk prevention, control and management were discussed from a global perspective. Based on the previous works, some experts from China were invited by CIOMS to undertake the compilation of this chapter. Meanwhile, a new causality assessment in DILI based on the integrated evidence chain(iEC) method was widely recognized by experts in China and abroad, and was recommended by this consensus. This paper briefly introduced the main contents, background, and characteristics of the Consensus on drug-induced liver injury. Significantly, a brief interpretation was illustrated to analyze the special highlights of Chapter 8, "Liver injury attributed to HDS", so as to provide practical references for the medical staff and the researchers who worked on either Chinese or Western medicine in China.

Establishment and clinical validation of an artificial intelligence YOLOv51 model for the detection of precancerous lesions and superficial esophageal cancer in endoscopic procedure / 中华肿瘤杂志

Objective: To construct the diagnostic model of superficial esophageal squamous cell carcinoma (ESCC) and precancerous lesions in endoscopic images based on the YOLOv5l model by using deep learning method of artificial intelligence to improve the diagnosis of early ESCC and precancerous lesions under endoscopy. Methods: 13, 009 endoscopic esophageal images of white light imaging (WLI), narrow band imaging (NBI) and lugol chromoendoscopy (LCE) were collected from June 2019 to July 2021 from 1, 126 patients at the Cancer Hospital, Chinese Academy of Medical Sciences, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, ESCC limited to the mucosal layer, benign esophageal lesions and normal esophagus. By computerized random function method, the images were divided into a training set (11, 547 images from 1, 025 patients) and a validation set (1, 462 images from 101 patients). The YOLOv5l model was trained and constructed with the training set, and the model was validated with the validation set, while the validation set was diagnosed by two senior and two junior endoscopists, respectively, to compare the diagnostic results of YOLOv5l model and those of the endoscopists. Results: In the validation set, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the YOLOv5l model in diagnosing early ESCC and precancerous lesions in the WLI, NBI and LCE modes were 96.9%, 87.9%, 98.3%, 88.8%, 98.1%, and 98.6%, 89.3%, 99.5%, 94.4%, 98.2%, and 93.0%, 77.5%, 98.0%, 92.6%, 93.1%, respectively. The accuracy in the NBI model was higher than that in the WLI model (P<0.05) and lower than that in the LCE model (P<0.05). The diagnostic accuracies of YOLOv5l model in the WLI, NBI and LCE modes for the early ESCC and precancerous lesions were similar to those of the 2 senior endoscopists (96.9%, 98.8%, 94.3%, and 97.5%, 99.6%, 91.9%, respectively; P>0.05), but significantly higher than those of the 2 junior endoscopists (84.7%, 92.9%, 81.6% and 88.3%, 91.9%, 81.2%, respectively; P<0.05). Conclusion: The constructed YOLOv5l model has high accuracy in diagnosing early ESCC and precancerous lesions in endoscopic WLI, NBI and LCE modes, which can assist junior endoscopists to improve diagnosis and reduce missed diagnoses.

MiR-4484 regulates the expression of integrin α 6 in gastric cancer tissues and its significance / 中华肿瘤杂志

Objective: To investigate the relationship between the expression of integrin α 6 (ITGA6), miR-4484 and the pathologic stage of gastric cancer. Methods: Gastric cancer tissues and normal gastric mucosa tissues adjacent to cancer (>5 cm from tumor margin) of 30 patients with primary gastric cancer who underwent direct surgical resection without adjuvant therapy from June to September 2017 in West China Hospital of Sichuan University were selected. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression levels of miR-4484 and ITGA6, western blot was used to detect the expression level of ITGA6 protein, dual luciferase reporter gene was used to verify the relationship between ITGA6 and miR-4484. Spearman's correlation analysis was used to determine the relationship between miR-4484 and ITGA6 expression levels in gastric cancer tissues. Results: The expression level of ITGΑ6 in gastric cancer (32.30±13.47) was higher than that in matched normal gastric tissues (24.55±10.25, P=0.015), the area under the receiver operating characteristic (ROC) curve was 0.660 and the diagnostic sensitivity and specificity were 43.3% and 96.7%, respectively. The expression level of miR-4484 in gastric cancer (4.11±2.87) was lower than that of matched normal gastric tissues (5.75±2.80, P=0.029), the area under the ROC curve was 0.690 and the diagnostic sensitivity and specificity were 30.0% and 86.7%, respectively. The expression level of miR-4484 was negatively correlated with ITGA6 in gastric cancer tissues (r=-0.621, P<0.001). The expression level of ITGA6 protein in gastric cancer tissues (0.65±0.19) was higher than that in normal adjacent tissues (0.26±0.12, P<0.001). Compared with ITGA6 3'UTR wild-type+ miR-NC group, ITGA6 3'UTR wild-type+ miRNA mimics group had lower luciferase activity (50.69±5.10, 34.00±1.19, P<0.001), while the luciferase activity of ITGA6 3'UTR wild-type+ ASO miR-4484 group was higher than that of ITGA6 3'UTR wild-type+ miR-NC group (82.44±6.37, 50.69±5.10, P<0.001), indicated that ITGA6 was the direct target gene of miR-4484. The expression levels of miR-4484 in T1, T2, T3 and T4 (4a and 4b) gastric cancer tissues were 9.98±2.24, 5.28±2.03, 2.92±2.04 and 4.11±2.87, respectively, with statistical significance (P<0.001). The expression levels of ITGA6 in N0, N1, N2 and N3 gastric cancer tissues were 29.55±8.32, 21.71±3.75, 24.60±8.79 and 40.69±15.83, respectively, with statistical significance (P=0.022). The expression levels of miR-4484 in N0, N1, N2 and N3 gastric cancer tissues were 5.01±3.52, 5.48±2.76, 5.88±1.83 and 2.30±1.56, respectively, with statistical significance (P=0.032). The expression levels of ITGA6 in M0 and M1 gastric cancer tissues were 26.28±7.66 and 52.08±8.12, respectively, with statistical significance (P<0.001). The expression levels of miR-4484 in M0 and M1 gastric cancer tissues were 4.95±2.74 and 1.34±0.80, respectively, with statistical significance (P<0.001). Conclusions: ITGA6 is upregulated in gastric cancer tissues, while miR-4484 is downregulated in the gastric cancer group, and its expression level is related to the clinicopathological features of gastric cancer. ITGA6 is the direct target gene of miR-4484, implicates that miR-4484 may inhibit the invasion and metastasis of gastric cancer by regulating the expression of ITGA6. Both miR-4484 and ITGA6 may be the new prognostic markers and potential therapeutic targets of gastric cancer.

CHINA PH ARMACY Volume 33，Number 13，July 15，2022 Semimonthly Table of Contents Discussion on development difficulties and countermeasures of complex preparations in China / 中国药房

OBJECTIVE To discuss the difficulties in t he development of complex preparations and puts forward solutions ，in order to provide some reference for the development and preparation of complex preparations. METHODS Based on the development status of complex preparations ，the challenges faced by the development of complex preparations were analyzed ，and the countermeasures for the development of complex preparations were proposed. RESULTS & CONCLUSIONS The development of complex preparations required high quality of personnel ，and was limited by pharmaceutical excipients ，delivery devices and pharmaceutical equipment. The preparation process was complex ，there were many quality control parameters and patent barriers. Complex preparation development enterprises need to pay more attention to talents ，pharmaceutical excipients ，delivery devices and pharmaceutical equipment ，and clarify the impact of key technology on preparation production and quality characteristics ；in addition，they need to strengthen independent research and development ，crack the patent layout of original research enterprises and protect their own innovative achievements. Domestic complex preparation development enterprises can combine imitation and innovation to develop complex preparation products with independent brands to better meet the needs of patients.

Clinical significance of monitoring parathyroid hormone in drainage fluid and serum after total thyroidectomy / 中华内分泌外科杂志

Objective:To observe the effect of different clinical factors on the level of parathyroid hormone (PTH) and to predict the possibility of permanent hypothyroidism (PHP) after total thyroidectomy (TT) by monitoring the levels of PTH in serum and drainage fluid after TT.Methods:Retrospective analysis was made on 150 patients who underwent TT for papillary thyroid carcinoma (PTC) in the Department of Thyroid Head and Neck Surgery in Jilin Cancer Hospital from Jan. 2020 to Aug. 2021. The changes of serum PTH were recorded at 1, 3, 7, 30 days and 6 months after surgery. The risk factors of postoperative hypoparathyroidism (HP) were investigated by single factor and multi factor methods. The impairment of parathyroid function was predicted combined with the level of PTH in the drainage fluid 1 day after operation.Results:After TT, serum PTH returned to normal value in most patients 1 month after operation. The proportion of PHP was 3.33% (5/150). Univariate analysis showed that bilateral central lymph node dissection, Hashimoto’s thyroiditis, tumor diameter ≥2 cm and intraoperative selective parathyroid autologous transplantation were risk factors for temporary hypoparathyroidism (THP). Multivariate analysis showed that BCND ( OR=0.322, P=0.001) , intraoperative selective parathyroid autograft ( OR=5.442, P=0.001) and tumor diameter ≥2 cm ( OR=2.247, P=0.003) were independent risk factors for THP. ROC curve was used to compare the predictive effect of postoperative serum and drainage PTH levels on postoperative PHP. The statistical results showed that the highest predictive effect of postoperative PHP was found on the first day of drainage PTH level within 1 week after operation (AUC 0.81) . 54 cases whose serum PTH was lower than normal value on the first day after operation were divided into 4 groups according to the level of PTH in drainage fluid from high to low. The results showed that the lower the level of PTH in drainage fluid, the greater the possibility of PHP ( P<0.05). Conclusions:Most of the patients with low PTH one month after operation develop PHP, while bilateral central lymph node dissection, intraoperative selective parathyroid transplantation, tumor diameter ≥2 cm are risk factors for THP after TT. If the serum PTH is lower than the normal value on the first day after operation, there is a possibility of PTH. The lower the PTH in the drainage fluid, the greater the possibility of PHP, which should be paid attention to in clinical practice.

Application and Prospect Analysis of Preparation Technology in Improving Antibacterial Activity of Traditional Chinese Medicine / 中国实验方剂学杂志

Pathogenic bacterial infection is one of the main clinical symptoms. Antibiotics are widely used in clinical practice to inhibit or kill the bacteria， fungi and other pathogenic microorganisms. However， with the massive use of antibiotics， drug-resistant strains continue to appear that make the antibacterial situation is becoming increasingly severe. Due to the advantages of multiple targets， multiple pathways and multiple components， traditional Chinese medicine （TCM） have gradually attracted more attention and were used in antibacterial treatment. However， some antimicrobial TCM have problems such as low solubility， poor stability， and low bioavailability. Improving and enhancing the antibacterial activity of TCM through preparation technology is one of the effective solutions. Based on this， two aspects of unilateral antibacterial TCM preparation technology and combination antibacterial preparation technology are introduced， including inclusion technology， nanotechnology， electrospinning， 3D printing and others. Distinctive features and specific application effects of these preparation technologies are explained firstly， and then their advantages and disadvantages are compared and analyzed. The review can be a useful reference for improving the antibacterial activity of TCM.

Occupational Health Risk Assessment of Benzene, Toluene, and Xylene in Shanghai / 生物医学与环境科学（英文）

Objective@#This study was designed to conduct a retrospective and systematic occupational health risk assessment (OHRA) of enterprises that used benzene, toluene, and xylene (BTX) in Shanghai, China.@*Methods@#All data for the study were obtained from 1,705 occupational health examination and evaluation reports from 2013 to 2017, and a semiquantitative model following Chinese OHRA guidelines (GBZ/T 298-2017) was applied for the assessment.@*Results@#The selected enterprises using BTX were mainly involved in manufacturing of products. Using the exposure level method, health risk levels associated with exposure to BTX were classified as medium, negligible, or low. However, the risk levels associated with benzene and toluene were significantly different according to job types, with gluers and inkers exhibiting greater health risks. For the same job type, the health risk levels assessed using the comprehensive index method were higher than those using the exposure level method.@*Conclusion@#Our OHRA reveals that workers who are exposed to BTX still face excessive health risk. Additionally, the risk level varied depending on job categories and exposure to specific chemicals. Therefore, additional control measures recommended by OHRA guidelines are essential to reduce worker exposure levels.

Objective Quantitation of EGFR Protein Levels using Quantitative Dot Blot Method for the Prognosis of Gastric Cancer Patients

Purpose@#An underlying factor for the failure of several clinical trials of anti-epidermal growth factor receptor (EGFR) therapies is the lack of an effective method to identify patients who overexpress EGFR protein. The quantitative dot blot method (QDB) was used to measure EGFR protein levels objectively, absolutely, and quantitatively. Its feasibility was evaluated for the prognosis of overall survival (OS) of patients with gastric cancer. @*Materials and Methods@#Slices of 2×5 μm from formalin-fixed paraffin-embedded gastric cancer specimens were used to extract total tissue lysates for QDB measurement. Absolutely quantitated EGFR protein levels were used for the Kaplan-Meier OS analysis. @*Results@#EGFR protein levels ranged from 0 to 772.6 pmol/g (n=246) for all gastric cancer patients. A poor correlation was observed between quantitated EGFR levels and immunohistochemistry scores with ρ=0.024 and P=0.717 in Spearman's correlation analysis. EGFR was identified as an independent negative prognostic biomarker for gastric cancer patients only through absolute quantitation, with a hazard ratio of 1.92 (95% confidence interval, 1.05–3.53; P=0.034) in multivariate Cox regression OS analysis. A cutoff of 208 pmol/g was proposed to stratify patients with a 3-year survival probability of 44% for patients with EGFR levels above the cutoff versus 68% for those below the cutoff based on KaplanMeier OS analysis (log rank test, P=0.002). @*Conclusions@#A QDB-based assay was developed for gastric cancer specimens to measure EGFR protein levels absolutely, quantitatively, and objectively. This assay should facilitate clinical trials aimed at evaluation of anti-EGFR therapies retrospectively and prospectively for gastric cancer.

Comparative study on metastatic lymph node radio and pathological lymph node stage in prognosis evaluation of patients with gastric cancer after radical resection / 中华内分泌外科杂志

Objective:To study the value of metastatic lymph node radio (rN) and pathological lymph node stage (pN) in evaluating the prognosis of patients after radical gastric cancer.Methods:The clinicopathological data of 491 patients who underwent radical gastrectomy in Tantai Yantaishan Hospital from Jan. 2013 to Dec. 2017 were retrospectively analyzed. X-tile software was used to group the metastatic lymph node radio by rN. According to the number of lymph node metastasis, pN stage was performed. The correlation between metastatic lymph node radio and other clinicopathological factors was assessed. The metastatic lymph node radio and the pathological lymph node stage in evaluating the prognosis of patients after radical gastric cancer were compared.Results:(1) X-tile analysis showed that the best cut-off values for the metastatic lymph node radio in this study were 0.14 (14%) and 0.63 (63%) . (2) According to the cut-off value, the 491 patients included in the study were divided into rN1 (256 cases) , rN2 (160 cases) , and rN3 (75 cases) three subgroups. The results of the analysis of differences showed that there were significant differencesbetween the groups in terms of tumor diameter, tumor location, surgical resection range, stage, lauren classification, degree of differentiation, pT, pN, vascular cancer emboulus, nerve invasion, and pathological TNM staging groups. (3) Comparison of rN and pN staging in evaluation of the prognosis of patients after radical gastric cancer: ①Kaplan-Meier survival analysis results showed that rN was better than pN. ② Both single factor and multivariate cox analysis showed that rN was an independent risk factor for the prognosis of gastric cancer. In univariate analysis, rN group HR=3.18 (95% CI 2.63-3.84, P<0.001) , pN stage HR=1.88 (95% CI 1.66-2.15, P<0.001) ; rN group HR=2.21 in multivariate analysis (95% CI 1.73-2.82, P<0.001) , pN staging HR=1.31 (95% CI 0.95-1.79, P=0.095) . ③The time-dependent ROC analysis showed that the prognostic ability of rN was better than pN staging before 52 months of postoperative follow-up, and pN staging was more advantageous after 52 months. ④The Lauren classification was used as a stratification factor for stratified analysis. The Kaplan-Meier survival curve indicated that rN was better than pN staging in intestinal, mixed and diffuse gastric cancer, and the AUC curve showed the prediction of rN in patients with mixed and diffuse gastric cancer was better than pN staging, while pN staging performance was slightly better in patients with intestinal gastric cancer. Conclusions:rN is an independent factor affecting the prognosis of patients after radical gastric cancer surgery. When judging the prognosis of patients within 52 months after radical gastric cancer, rN has a better prognostic value than pN. In patients with mixed and diffuse gastric cancer in the Lauren classification, rN shows better prognostic value.

Improvement Effects of Chelidonine on CCl 4-induced Hepatic Fibrosis Model Rats and Its Mechanism / 中国药房

OBJECTIVE：To study the improvement eff ects and p otential mechanism of chelidonine on CCl 4-induced hepatic fibrosis model rats. METHODS ：According to the random number table method ，a total of 48 rats were randomly divided into normal control group ，model group ，chelidonine low-dose ，middle-dose and high-dose groups （0.125，0.25，0.50 mg/kg），positive control group （Liver-protecting tablet ，0.42 g/kg），with 8 rats in each group. Except for normal control group ，other groups were given CCl 4-olive oil solution intraperitoneally for 8 weeks to induce hepatic fibrosis model. From the fifth week of modeling ， normal control group and model group were given water intragastrically ；administration groups were given relevant medicine intragastrically，once a day ，for consecutive 10 weeks. After last intragastric administration ，hepatic index of rats was calculated. The levels of aspartate aminotransferase （AST），alanine aminotransferase （ALT）and hyaluronic acid （HA）in serum and the level of hydroxyproline （Hyp）in liver tissue were determined. The staining of collagen fibrin in rat liver was observed. The protein expression of α-smooth muscle actin （α-SMA），microtubule-associated protein 1 light chain 3（LC3）and p 62 as well as the phosphorylation level of phosphoinositide 3 kinase（PI3K），protein kinase B （Akt）and mammalian target of rapamycin （mTOR）in liver tissue were determined ；mRNA expression corresponding to above protein were also determined. RESULTS ：Compared with normal control group ，the hepatic index ，the serum levels of AST ，ALT，HA and Hyp ，the percentage of positive staining area for collagen fibrin ，the mRNA and protein expression of α-SMA and LC 3- Ⅱ were increased significantly （P＜0.05）. Protein expression of p 62，phosphorylation levels of PI 3K，Akt and mTOR as well as mRNA expression of p 62，PI3K，Akt and mTOR were significantly down-regulated （P＜0.05）. Compared with model group ，phosphorylation levels of PI 3K and mTOR were decreased significantly in chelidonine low-dose group （P＜0.05）. The changes of above indexes in chelidonine middle-dose and high-dose groups （except for liver index ， HA level in middle-dose group ） were reversed significantly （P＜0.05）. CONCLUSIONS：Chelidonine can attenuate CCl 4-induced liver fibrosis in rats ；the mechanism of it may be associated with activating PI 3K/Akt/mTOR signaling pathway and inhibiting autophagy.

The molecular mechanism of ginkgolide B regulating the expression of long-chain fatty acid metabolism-related proteins and antioxidant therapy for non-alcoholic fatty liver disease / 药学学报

This study investigated the effects of ginkgolide B on the long-chain fatty acid metabolism-related enzyme protein peroxisome proliferators-activated receptors α (PPARα), long-chain specific acyl-CoA dehydrogenase (LCAD), carnitine palmitoyl transterase-1 (CPT-1), and acyl coenzyme A oxidase 1 (ACOX1) expression in the liver of rats with non-alcoholic fatty liver disease (NAFLD). All the animal welfare and experimental procedures are in accordance with the regulations of the Animal Ethics Committee of Yunnan University of Traditional Chinese Medicine. After successfully building the rat model of non-alcoholic abnormal liver disease, the rats were divided into the model group, the simvastatin group, and the low-dose, middle-dose, and high-dose groups of ginkgolide B according to random number method, and were given corresponding drug treatment 4 weeks. We detected liver pathological indicators and determined blood lipids, transaminase and anti-oxidation indexes. Western blot and RT-PCR assays were used to detect the protein and mRNA levels of PPARα, LCAD, CPT-1, and ACOX1 in livers. The results showed that: ① the liver histopathology showed that the liver slices of the model group had obvious structural disorder, the nucleus was squeezed, and there were obvious fat vacuoles. The treatment groups improved significantly compared with the model group; ② compared with the normal group, the liver function and blood lipid indexes of the model group increased significantly, while the anti-oxidation indexes decreased significantly. Compared with the model group, each treatment groups were significantly improved; ③ compared with the normal group, the protein and mRNA expression levels of PPARα, ACOX1, CPT-1, and LCAD in the model group were significantly reduced, compared with the model group, those indexes in the treatment groups were significantly up-regulated. This study found that ginkgolide B could regulate the expression of long-chain fatty acid metabolism-related proteins PPARα, ACOX1, CPT-1, and LCAD, meanwhile improve the body's antioxidant capacity, thereby reduce blood lipids, further improve liver function and protect the liver.

Immunomodulatory effects of flazin from Crassostrea sikamea on splenic lymphocytes of Sprague-Dawley rats / 中国天然药物

Crassostrea sikamea (C.sikamea) is an important edible and medicinal seafood in China. In the present study, a compound named flazin was separated and identified from the ethyl acetate extract of C.sikamea (EAECs) for the first time. In addition, the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra zolium (MTS) assay revealed that EAECs and flazin inhibited the transformation of splenic lymphocytes in vitro. Moreover, flazin (20 μg·mL

Landscape of Hepatobiliary Adverse Drug Reactions Related to Preparations Containing Psoraleae Fructus and Its Application in Pharmacovigilance / 中国结合医学杂志

OBJECTIVE@#To analyze clinical feature and information of medication to explore the risk signals of preparations containing Psoraleae Fructus (BGZP) related with hepatobiliary adverse drug reactions (ADR), in order to reinforce pharmacovigilance.@*METHODS@#A retrospective study was conducted based on hepatobiliary ADR related with BGZP from the China Adverse Drug Reaction Monitoring System in years from January 2012 to December 2016. Serious and general ADRs were analyzed and assessed.@*RESULTS@#There were 355 cases of hepatobiliary ADR related to BGZP. Both the amount of cases and the proportion of serious ADR showed an increasing growth by years (P<0.05). It was found that 10.43% of 355 cases may be involved with irrational drug use, including overdose, repeated medication, and combination of multiple drugs. There were 190 cases which used BGZP (non-combination), and they were mainly for common in diseases caused by abnormal immune activation (accounting for 40.53% of the total cases). Especially at the age group with the most cases with age of 41-50 years, the cases associated with immunological diseases of female were obviously more than that of male (P<0.05). The latency of hepatobiliary ADR related to BGZP ranged from 1 to 386 days, and the median latency was 27.5 days, along with the range of cumulative dose (0.45-520.02 g) as well as the daily dose (0.09-2.64 g/d) after the conversion.@*CONCLUSIONS@#Cases of hepatobiliary ADR related to BGZP showed significant individual differences, and there was no correlation between drug usage duration and dosage and the occurrence of hepatobiliary ADR. It may be similar with idiosyncratic drug-induced liver injury, and recommended that BGZP should be used with more caution under monitoring liver function, especially in female patients with immunological diseases.