BACKGROUND:Shujin Jiannao Prescription is an empirical formula for the treatment of cerebral palsy in Dongzhimen Hospital,Beijing University of Chinese Medicine,with clear clinical efficacy,but the specific mechanism needs to be elucidated. OBJECTIVE:To explore the possible mechanism of Shujin Jiannao Prescription in treating cerebral palsy. METHODS:Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into a normal group(n=12)and a model group(n=52).An animal model was established by the Rice-Vannucci method.After successful modeling,52 model rats were randomly divided into control model group(n=12),minocycline group,and the low-,medium-,and high-dose groups of the Shujin Jiannao Prescription(n=10 per group).Rats in the minocycline group were given 40 mg/kg·d minocycline by gavage;rats in the low-,medium,and high-dose groups were given 4,8,and 16 g/kg·d Shujin Jiannao Prescription granules by gavage,respectively;and rats in the normal group and control model group were given an equal dose of normal saline by gavage.Medication in each group was given once a day for 1 week.The rats in each group were evaluated behaviorally using suspension test,abnormal involuntary movement score,and Bederson score.The pathological changes of the cerebral cortex were observed by hematoxylin-eosin staining.The levels of tumor necrosis factor α,interleukin 1β,and interleukin 10 in the cerebral cortex were determined using ELISA.The positive expressions of Janus kinase 2(JAK2),phosphorylated Janus kinase 2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3)in the cerebral cortex were detected using immunohistochemistry.The protein expression levels of JAK2,p-JAK2,and p-STAT3 were detected using western blot. RESULTS AND CONCLUSION:Compared with the normal group,the suspension test score and involuntary movement score were decreased in the control model group(P＜0.01 or P＜0.05).The pathological results showed structural disruption of nerve cells,formation of large numbers of vacuoles,cell swelling,and increased intercellular space in the control model group.In addition,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were significantly increased(P＜0.01),the expression of interleukin 10 was decreased(P＜0.05),and the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly increased(P＜0.01)in the control model group compared with the normal group.Compared with the model group,minocycline and Shujin Jiannao Prescription at each dose could improve the behavioral indexes of rats(P＜0.01 or P＜0.05)and ischemic-hypoxic pathological changes were attenuated,with only a small amount of necrotic nerve cells and a few vacuoles,and reduced intercellular space.Moreover,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were decreased in each drug group compared with the control model group(P＜0.05),while the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly decreased(P＜0.01).The most obvious improvement was observed in the high-dose Shujin Jiannao Prescription group.To conclude,Shujin Jiannao Prescription can inhibit inflammation in the cerebral cortex of rats with hypoxic-ischemic brain injury.The mechanism may be related to the regulation of the JAK2/STAT3 signaling pathway.

BACKGROUND:Perinatal hypoxic-ischemic brain injury is one of the most common causes of cerebral palsy.Shujin Jiannao Prescription is an experienced formula for treating cerebral palsy and improving blood supply to the brain developed by the Dongzhimen Hospital,Beijing University of Chinese Medicine. OBJECTIVE:To explore the possible mechanism of Shujin Jiannao Prescription in treating hypoxic-ischemic cerebral palsy. METHODS:Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into six groups.There were 12 rats in each of the control and model groups as well as 10 animals in each of the minocycline group,and the low-,medium-,and high-dose groups of Shujin Jiannao Prescription.The neonatal rat ischemic-hypoxic cerebral palsy model was established in all groups except for the control group.After successful modeling,rats in each drug group were respectively gavaged with minocycline and Shujin Jiannao Prescription at a dose of 4,8,and 16 g/kg per day for 1 week.Body mass of rats was measured and behavioral changes were detected before and after drug administration.Hematoxylin-eosin staining was used to observe the histomorphology of hippocampal CA1 region of rat brain tissue,and immunohistochemistry and western blot were used to detect the expression levels of Bcl-2,Bax,and Caspase-3 in the brain tissue of rats. RESULTS AND CONCLUSION:Compared with the model group,medium-and high-dose Shujin Jiannao Prescription significantly increased the body mass of rats(P<0.05).Compared with the model group,minocycline effectively prolonged the suspension time of ischemic-hypoxic cerebral palsy rats(P<0.05),while medium-and high-dose Shujin Jiannao Prescription significantly prolonged the suspension time,shortened the inclined plane test time,and increased the Longa score of rats(P<0.05).The pathological results showed that after drug intervention,only a small number of neuronal cells in the brain tissue of rats were necrotic,the cells were more neatly arranged,the cell structure was more complete,and only part of the cell nuclei became smaller.Compared with the model group,minocycline and medium-and high-dose Shujin Jiannao Prescription reduced the expression of Bax Caspase-3(P<0.05),medium-and high-dose Shujin Jiannao Prescription increased the expression of Bcl-2(P<0.05),and Bcl-2/Bax protein expression was increased in minocycline and three Shujin Jiannao Prescription groups(P<0.05).In addition,the protein expression was increased in a dose-dependent manner after intervention with Shujin Jiannao Prescription,and there was no significant difference between the minocycline and three Shujin Jiannao Prescription groups(P>0.05).To conclude,the mechanism by which Shujin Jiannao Prescription treats ischemic-hypoxic cerebral palsy in rats may be to enhance the expression of anti-apoptotic protein Bcl-2,inhibit the expression of pro-apoptotic protein Bax,and reduce the expression of Caspase-3,ultimately inhibiting the apoptosis of hippocampal neuronal cells in rats with cerebral palsy.Within a certain range,the higher dose of Shujin Jiannao Prescription indicates the better therapeutic effect,and the high-dose Shujin Jiannao Prescription is as effective as minocycline.

Objective:To investigate the effects of hyperbaric oxygen therapy (HBOT) on neurological function, Th17/Treg levels, and TLR2/NF-κB pathway in children with viral encephalitis (VE).Methods:A total of 76 children with VE admitted to the Dadukou People’s Hospital between April 2017 and April 2019 were selected as the research subjects and randomly assigned to two groups ( n=38) by the random number table method. The children in the control group received conventional treatment, and those in the HBOT group additionally received HBOT. The clinical treatment effects, the results of electroencephalogram (EEG) examination, the mini-mental state examination(MMSE), the serum inflammatory factors, the central nerve specific protein (S100β), the neuron-specific enolase (NSE), the peripheral blood Th17/ regulatory T cells (Treg), and TLR2/NF-κB pathway levels were compared. There were no significant differences in those indicators between the two groups before treatment ( P>0.05). Results:The time period for the clinical symptoms to disappear in the HBOT group was significantly shorter than that in the control group ( P<0.05). The times of seizure onset in the HBOT group were significantly less than those in the control group ( P<0.05). After treatment, the proportions of moderate and severe EEG abnormalities in the HBOT group were significantly lower than those in the control group ( P<0.05), the proportion of EEG returning to normal state was significantly higher than that in the control group ( P<0.05), and the recovery time period of EEG in the HBOT group was significantly shorter than that in the control group ( P<0.05). After treatment, the MMSE score of the HBOT group was higher than that of the control group [(28.16±8.29)>(20.21±4.40), P<0.05]. The levels of IL-1, CRP, S100β, and NSE in the HBOT group were significantly lower than those in the control group ( P<0.05). After treatment, the level of Th17 in the HBOT group was significantly lower than that in the control group [(0.024±0.004)% vs. (0.028±0.01)%, P<0.05], and the level of Treg was significantly higher than that in the control group [(0.016±0.003)% vs. (0.014±0.004)%, P<0.05]. The levels of TLR2, Myd88, and NF-κB protein in the HBOT group were significantly lower than those in the control group ( P<0.05). No HBOT-related adverse reaction was found in the HBOT group. Conclusion:The treatment combined with HBOT can improve the curative effect in the children with VE, reduce the times of seizure onset, and protect brain. This may be related to the role of HBOT in inhibiting TLR2/NF-κB pathway and regulating the balance of Th17/Treg.

Objective:To investigate the effects of hyperbaric oxygen therapy (HBOT) on neurological function, Th17/Treg levels, and TLR2/NF-κB pathway in children with viral encephalitis (VE).Methods:A total of 76 children with VE admitted to the Dadukou People’s Hospital between April 2017 and April 2019 were selected as the research subjects and randomly assigned to two groups ( n=38) by the random number table method. The children in the control group received conventional treatment, and those in the HBOT group additionally received HBOT. The clinical treatment effects, the results of electroencephalogram (EEG) examination, the mini-mental state examination(MMSE), the serum inflammatory factors, the central nerve specific protein (S100β), the neuron-specific enolase (NSE), the peripheral blood Th17/ regulatory T cells (Treg), and TLR2/NF-κB pathway levels were compared. There were no significant differences in those indicators between the two groups before treatment ( P>0.05). Results:The time period for the clinical symptoms to disappear in the HBOT group was significantly shorter than that in the control group ( P<0.05). The times of seizure onset in the HBOT group were significantly less than those in the control group ( P<0.05). After treatment, the proportions of moderate and severe EEG abnormalities in the HBOT group were significantly lower than those in the control group ( P<0.05), the proportion of EEG returning to normal state was significantly higher than that in the control group ( P<0.05), and the recovery time period of EEG in the HBOT group was significantly shorter than that in the control group ( P<0.05). After treatment, the MMSE score of the HBOT group was higher than that of the control group [(28.16±8.29)>(20.21±4.40), P<0.05]. The levels of IL-1, CRP, S100β, and NSE in the HBOT group were significantly lower than those in the control group ( P<0.05). After treatment, the level of Th17 in the HBOT group was significantly lower than that in the control group [(0.024±0.004)% vs. (0.028±0.01)%, P<0.05], and the level of Treg was significantly higher than that in the control group [(0.016±0.003)% vs. (0.014±0.004)%, P<0.05]. The levels of TLR2, Myd88, and NF-κB protein in the HBOT group were significantly lower than those in the control group ( P<0.05). No HBOT-related adverse reaction was found in the HBOT group. Conclusion:The treatment combined with HBOT can improve the curative effect in the children with VE, reduce the times of seizure onset, and protect brain. This may be related to the role of HBOT in inhibiting TLR2/NF-κB pathway and regulating the balance of Th17/Treg.

OBJECTIVE：To struc turally modify shikimic acid ，and to investigate the reversal effects of its derivatives on paclitaxel-resistant human breast cancer cells MCF- 7/PTX. METHODS ：Using shikimic acid as the lead structure ，1-position carboxyl group was structurally modified to synthesize a series of shikimic acid derivatives through esterification ，amidation， hydrogenation and reduction ，etc. Using non-drug resistant cells MCF- 7 as reference ，MTT assay was used to screen derivatives with inhibitory activity as well as half-inhibitory concentration （IC50）and reversal index （RI）of derivatives to MCF- 7/PTX. With the drug resistance-related transgelin 2 as the target ，the molecular docking of the active derivatives with the drug resistance-related protein was carried out by using Glide 1.0 computer-aided design software. RESULTS ：Totally 15 derivatives were obtained （T1-T15）， of which T 4-T15 were obtained for the first time. MTT assay showed that （3R， 4S， 5R） -N-benzyl-3， 4， 5-trihydroxy-1-cyclohexene-1-formamide（T7），（3R，4S，5R）-N-（3，4，5-trihydroxy-1-cyclohexenylmethyl）-benzylamine（T14）， （3R，4S，5R）-3，4-O-isopropyl-5-O-acetyl-1-cyclohexene-1-methyl formate （T15）inhibited MCF- 7 and MCF- 7/PTX cells to a certain extent ；IC50 values of T 7，T14 and T 15 combined with pacliaxel to MCF- 7/PTX cells were significantly lower than that in negative control （Paclitaxel alone ）group（P＜0.05）. RIs of T 14 and T 15 were higher ，and RIs of the highest dose were 8.8 and 9.3， which were equivalent to positive control verapamil （10.8）. Th e results of molecular docking showed that the hydroxyl groups at positions 3，4 of T 7 could form multiple hydrogen bonds with ； Arg625 and Asp 627 in the catalytic region of transgelin 2. In addition to the hydrogen bond mentioned above at T 7，the mail：batistuta28@126.com secondary amine side chain at position 1 of T 14 could also form hydrogen bond with Glu 657 of transgelin 2. When the hydroxyl group on the T 15 mother nucleus was derived from the donor group ，the binding of the hydroxyl group to transgelin 2 was closer and the inhibition was enhanced. CONCLUSIONS ： The derivatives T 7，T14 and T 15 have certain reverse activity to paclitaxel-resistant human breast cancer cells. The polyhydroxy structure of the mother nucleus is the main structural region of the hydrogen bond between shikimic acid and its derivatives and transgelin 2. The derivation of its power supply group or the introduction of secondary amines and hydrophobic groups into the 1-carboxyl group of shikimic acid is benifit for enhancing the drug resistance reversal effect of derivative .

As one of the most common pathogens in aquatic animals, Aeromonas hydrophila exhibits a wide range of pathogenicity. Due to factors like unreasonable use of antibiotics and horizontal gene transfer mediated by plasmids, many resistant strains of Aeromonas hydrophila were isolated from ready-to-eat seafood products in retail markets, supermarkets and restaurants. These strains carry many resistance genes. Therefore, it is essential to explore the key control points, and seek for prevention and control strategies so as to effectively alleviate antibiotic resistance. We review here the prevalence of drug resistance of Aeromonas hydrophila in China, and its main infection and resistance mechanisms, and the main means and strategies for reducing and preventing drug resistance. We also address further research directions and focus on drug resistance in Aeromonas hydrophila of the aquatic product.
Aeromonas hydrophila ; drug effects ; Animals ; Anti-Bacterial Agents ; pharmacology ; China ; epidemiology ; Drug Resistance, Bacterial ; Fish Diseases ; epidemiology ; microbiology ; Fisheries ; Fishes ; Gram-Negative Bacterial Infections ; epidemiology ; microbiology ; Research

The paper introduced the theory of the standard score and its application in instructional supervision and analyzed the difference between the standard score and original score in instructional supervision recording and revealed the reasons behind the difference.Besides,the paper pointed out the advantages which included scientificity and stability,providing information of the grade level,being suitable for longitudinal comparison and the crosswise comparison,and disadvantages such as complex calculation and depending on the distribution of original records.Finally,the paper put forward some recommendations on using standard score in instructional supervision:keeping the stability of the supervision expert team,insurance of supervision times,carrying out classified supervision and viewing the scores in its entirety.

Objective To investigate the real-life experience of young patients with gynecological tumor before chemotherapy, and provide evidence for targeted interventions. Methods A total of 11 patients with gynecological tumor who would receive chemotherapy were selected as the research object, and qualitative research was used to analyze the data and refine the theme from physiology, psychology and society three aspects. Results Six themes were drawn by analyzing, sorting and refining, and they were:physical discomfort, negative emotions on chemotherapy, sense of uncertainty and insecurity about the future, burden of self-feeling, strong demand for knowledge and information related to chemotherapy, and active coping style. Conclusions Young patients with gynecological tumor will have physical discomfort and negative emotions before chemotherapy, so they need support from hospital, family and society. Nursing staff should understand their physiological and psychological response at this stage, and provide targeted nursing interventions and psychological counseling.

Objective To observe the clinical effects of modified Shengxian decoction in the treatment of thyroid cancer postoperative hypothyroidism patients.Methods 60 patients of thyroid cancer postoperative hypothyroidism due to deficiency of spleen and kidney were randomly divided into a control group and a treatment group.The control group (28 cases) was by levothyroxine sodium tablets conventional treatment,while the treatment group (32 cases) was treated with Shengxian decoction based on thecontrol group.The changes of the symptom integral and HAMD-17 were observed between two groups before and after treatment.Results After treatment,the total effective rate was 87.5％ in the treatment group and 64.3％ in the control group,the clinical effect of treatment group was significantly better than the control group (x2=4.499,P＜ 0.05).After treatment,the total score of HAMD-17 was 6.8±2.3 in the treatment group and 15.8±2.1 in the control group,both significantly improved than that before the treatment (which were 19.4±1.45 and 18.9± 1.32 respectively).Compared with the control group,the treatment group improved significantly (P＜ 0.01).Conclusion Shengxian decoction plus western medicine has remarkable curative effect in the treatment of thyroid cancer postoperative hypothyroidism,it can improve the depressive state of patients and improve the quality of life.

Objective To investigate the significance of cortactin in primary liver cancer. Methods Fiftythree paraffin embedded primary liver cancer specimens were collected at General Hospital of Air Force of PLA from January 2002 to May 2008. The expression of cortactin was detected by immunohistochemistry, and the relationship between cortactin expression and clinicopathologic parameters was analyzed. All data were analyzed via Wilcoxon rank sum test and Spearman rank correlation analysis. Results There was a significant difference in cortactin expression among tumor capsule integrity, TNM staging, portal vein tumor thrombus and extrahepatic metastasis (u =2. 19, 3. 584, 2. 796, P ＜ 0.05 ). There was a positive correlation between tumor invasion and cortactin expression ( r = 0. 5794, P ＜ 0.05 ). Conclusions Overexpression of cortactin may be one of the factors enhancing the invasion of primary liver cancer. The level of cortactin expression can be used in evaluating the invasive potential of primary liver cancer.