Depression is one of the common and serious complications after stroke. Post-stroke depression (PSD) is associated with poor outcomes and increased mortality. The American Heart Association/American Stroke Association guidelines for the early management of patients with acute ischemic stroke recommend that pharmacological therapy should be administered to patients with PSD. This article reviews the pharmacological therapy for PSD.

【Objective】 To explore the risk of Alzheimer′s disease (AD) transmitted by blood transfusion. 【Methods】 There were 10 APP/PS1 mice of 3, 6 and 9 months old, half female and half male, and the cognitive and behavioral abilities of C57 mice of the same age were measured, and the blood of the oldest APP/PS1 mice with no behavioral changes were collected to detect the contents of Aβ40 and Aβ42. The polymers Aβ40 and Aβ42 were prepared and Western blotting analysis was conducted. Kunming mice aged from 6 to 7 months were randomly divided into 6 groups (10 mice/ group, half male and half female). The blood of APP/PS1 mice was injected intravenously in experimental group 1-2(100 μL/mouse) with high frequency injection (3 times/week) and low frequency injection (1 time/week), respectively. In experimental group 3-4, Aβ40 and Aβ42 polymerized mixture (100 μL/mouse) were injected in high frequency and low frequency, respectively. The control group 1-2 was injected with the same amount of normal saline, with high frequency and low frequency, respectively. The above groups were injected for 4 weeks, and the cognitive and behavioral abilities were tested and analyzed one week after injection. Finally, the contents of Aβ40 and Aβ42 in blood of Kunming mice were detected. 【Results】 Change in cognitive and behavioral ability showed in 9 months old APP/PS1 mice, but not in 3 and 6 months old APP/PS1 mice. The contents of Aβ40 and Aβ42 (pg/mL) in blood of 6-7 months old APP/PS1 mice were 418.40±2.18 and 15.68±0.20, respectively. Except for monomers, most of the polymerized mixtures of Aβ40 and Aβ42 were dimers and trimers. In both high frequency and low frequency, Kunming mice transfused with blood of APP/PS1 mice (experimental group 1-2) showed a certain degree of anxiety-like behavior and short-term memory shortening in open-field test and conditioned fear test, but without significant difference. There was no significant difference in open field test, new object recognition, Barnes maze and cognitive behavior analysis of conditioned fear between experimental group 3-4 and the control group. The levels of blood Aβ40 and Aβ42(pg/mL) of Kunming mice detected by ELISA were 10.30±0.08 and 3.360±0.005, respectively, and there was no significant difference between the two groups. 【Conclusion】 Blood transfusion of APP/PS1 mice and the mixture of Aβ40 and Aβ42 have no significant effect on the cognitive function of healthy Kunming mice in a short time, and the risk of AD transmission is relatively low.

OBJECTIVE To analyze the patterns and characteristics of drug-related administrative penalty cases with medical institutions as parties from 2020 to 2022 in order to further improve drug management in medical institutions. METHODS A retrospective statistical analysis was used to summarize the drug-related administrative penalty decisions with medical institutions as parties， and to match them with the provisions of the Drug Administration Law （2019 version） for statistical analysis. RESULTS There were 144 complete administrative penalty decisions with medical institutions as parties. Analyzed by cause， 126 cases of administrative punishment for inferior drugs accounted for 87.50%， of which expired drugs accounted for more than 50.00% of the inferior drug cases； 15 cases （10.42%） were for purchasing drugs from enterprises or individuals not qualified to operate drugs. Analyzed by the range of punishment amount of the cases， 34 cases （23.61%） resulted in lighter penalties， while 81 cases （56.25%） resulted in reduced penalties. CONCLUSIONS There are extremely few medical institutions that have received administrative penalties for drug management violations. Medical institutions should strengthen the awareness of law-abiding， and know the red line of drug management and the illegal behavior that is easy to occur， so as to better strengthen drug quality management.

Objective:To investigate whether silencing signal transducer and activator of transcription 6 (STAT6) with siRNA can inhibit eosinophilic inflammation of sinonasal mucosa in a mouse model of eosinophilic chronic rhinosinusitis (ECRS).Methods:The study was conducted from March to September in 2022. Forty-eight female BALB/c mice were randomly divided into four groups: the control group, the Vehicle (transfection reagent)-treated group, the Scramble siRNA (Control siRNA)-treated group, and the STAT6 siRNA-treated group, with twelve mice in each group. An ovalbumin (OVA)-staphylococcal enterotoxin B (SEB)-induced ECRS murine model was established. SiRNA prepared in Lipofectamine was locally administered to the nasal cavity. After administration, samples of the peripheral blood and sinonasal mucosa were collected. Eosinophils in peripheral blood were detected by hematology analyzer. Total and OVA-specific IgE (OVA-sIgE) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Mucosal levels of cytokines and chemokines, including interleukin (IL)-5, IL-17A, interferon-γ (IFN-γ) and eotaxin-1, were also measured using ELISA. Mucosal histological changes of eosinophil infiltration were examined using hematoxylin, and eosin staining, and tissue eosinophil count was performed using a microscope under a high-power field (HPF). Tissue expression of STAT6 and phosphorylated STAT6 (p-STAT6) was detected with the western blot method. Immunofluorescence staining was used to localize the expression of p-STAT6 in sinonasal mucosa. Statistical analysis was conducted using SPSS 18.0 software.Results:Peripheral blood eosinophil count, percentage of peripheral blood eosinophil, total serum IgE level, and serum OVA-sIgE level in the STAT6 siRNA-treated group [(0.318±0.045)×10 3/μl, (3.667±0.479)%, (102.070±13.205) ng/ml, and (38.870±7.352) ng/ml] were significantly different from those of the Vehicle-treated group [(0.532±0.049)×10 3/μl, (6.710±1.061)%, (203.102±29.653) ng/ml, and (74.575±6.432) ng/ml, Z value was -2.56, -2.24, -2.40, and -2.56, respectively, all P<0.05] and Scramble siRNA-treated group [(0.493±0.036)×10 3/μl, (5.858±0.872)%, (189.964±30.042) ng/ml, and (80.935±8.358) ng/ml, Z value was -2.17, -2.08, -2.24, and -2.72, respectively, all P<0.05]. Besides, IL-5 and eotaxin-1 levels in the STAT6 siRNA-treated group [(312.279±34.281) pg/ml and (25.297±4.323) pg/ml] were significantly lower than those in the Vehicle-treated group [(689.667±31.905) pg/ml and (68.278±6.485) pg/ml, Z value was -2.73 and -2.88, respectively, both P<0.01] and Scramble siRNA-treated group [(661.783±42.094) pg/ml and (63.015±7.416) pg/ml, Z value was -2.72 and -2.81, respectively, both P<0.01]. Tissue eosinophil count in sinonasal mucosa was (29.132±4.163)/HPF in the STAT6 siRNA-treated group, and were significantly less than those in the Vehicle-treated group [(78.050±7.912)/HPF, Z=-2.88, P<0.01] and Scramble siRNA-treated group [(73.864±8.671)/HPF, Z=-2.72, P<0.01]. The expression level of STAT6 protein (0.105±0.021) was significantly decreased in the mice treated with STAT6 siRNA compared with PBS, Vehicle, and Scramble siRNA (0.232±0.037, 0.243±0.039, and 0.228±0.032, Z value was -2.25, -2.49, and -2.56, respectively, all P<0.05). Corresponding, p-STAT6 protein level (0.292±0.038) was markedly decreased by the introduction of STAT6 siRNA, the difference was statistically significant as compared with the Vehicle-and Scramble siRNA-treated groups (0.613±0.046 and 0.641±0.050, Z value was -2.81 and -2.88, respectively, both P<0.01). Immunofluorescence staining showed that p-STAT6 was mainly located in the nucleus of nasal epithelial cells and inflammatory cells. The green fluorescence of p-STAT6 expression in sinonasal mucosa in the STAT6 siRNA-treated group was weaker than that in the Vehicle-and Scramble siRNA-treated groups. Conclusion:Intranasal administration of STAT6 siRNA can significantly downregulate STAT6 expression, decrease p-STAT6 level, and prohibit the development of Th2-skewed ECRS.

【Objective】 To investigate the effect of intravenous immunoglobulin(IVIG) with different Aβ antibody content on the cognitive function of Alzheimer′s disease model mice. 【Methods】 IVIG from 8 domestic blood products companies were selected. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of Aβ40/42 antibody. Three kinds of IVIG with high, middle and low Aβ42/40 antibody levels were selected to treat 3xTg-AD mice. Forty 3-month-old 3xTg-AD mice were randomly divided into 4 groups with 10 mice in each group(half male and half female). Three treat groups were intraperitoneally injected with three kinds of IVIG with 1g·kg^-1 for 12 weeks(twice a week). The controls were injected with the same volume of saline. Behavioral tests were performed immediately by using the mouse behavior analysis system after a total of 24 injections. 【Results】 The concentrations of antibodies(μg/mL) against Aβ40 monomer in IVIG ranged 0.7±0.05 to 3.1±0.05, concentrations of antibodies against Aβ40 oligomer ranged 11.7±0.7 to 32.0±2.2, concentrations of antibodies against Aβ42 monomer ranged 1.8±0.1 to 27.9±0.3, and concentrations of antibodies against Aβ42 oligomeric ranged 2.3±0.1 to 49.4±2. High(IVIG-1), medium(IVIG-8) and low(IVIG-6) IVIG were selected for mice study. In the open field test, the time of four groups of mice entering the central area(s) was 0.5±0.9, 23.4±6.1(P<0.0001), 4.6±2.8 and 2.6±2.3, respectively; the number of feces(grains) was 1.6±0.7(P<0.0001), 1.2±0.4(P<0.0001), 2.4±0.5(P<0.001) and 3.8±0.8, respectively. In the novel object recognition test, the scores of exploring new objects were 71.3±29.5(P<0.05), 71.8±20.5(P<0.05), 75.9±26.9(P<0.01) and 25.6±23.7, respectively. In the Barnes maze test, the time of exploring the target hole in the IVIG-8 group was significantly longer than that in the control on the 6^th day(50.3±19.3 vs 21±14.6, P<0.05) and the 13^th day(58.2±20.9 vs 19.2±15.9, P<0.005), but there was no significant difference between the IVIG-1, 6 groups and the control. 【Conclusion】 There is a significant difference in the level of Aβ40/42 antibody among 8 kinds of domestic IVIG. Domestic IVIG could improve the cognitive function of 3-month-old 3xTg-AD mice after continuous intervention for 3 months. The improvement effect, however, was related to the Aβ antibody in IVIG, but not to the antibody concentration.

Objective To investigate the effect of curcumin on proliferation and apoptosis of human nasopharyngeal carcinoma (NPC) cell line CNE-2.Methods The CNE-2 cells were treated by by different concentrations (0,10,20,40,60 μmol/L) of curcumin.The proliferation activity of CNE-2 cells was detected by MTT assay,the cell cycle and apoptosis rate of CNE-2 were detected by using the flow cytometry (FCM),and the apoptosis was observed by Hoechest33258 fluorescence staining.Results Curcumin could significantly inhibit the proliferation of CNE-2 cells,moreover which was increased with curcumin concentration increase,the inhibitory rate of CNE-2 cells showed an increasing trend (P＜0.05),the half inhibitory concentrations (IC50) of curcumin acting on CNE-2 cells at 24,48,72 h were (23.54 ± 0.36),(18.31 ± 0.42) and (8.56 ± 0.37) μmol/L respectively.Curcumin could significantly inhibit the proliferation effect of CNE-2 cells,showing the apparent concentration and time dependence.The FCM detection results showed that in treating CNE-2 cells by 0,10,20,40,60 μmol/L of curcumin,the apoptosis rate was increased with the curcumin concentration increase;the fluorescence staining results showed that CNE-2 cells without curcumin treatment were round or oval,the cell nucleis were uniform in size,chromatin distribution showed the homogeneous light blue fluorescence;after 24 h of 10 μmol/L curcumin treatment,the CNE-2 cell body was shrunk and cell nuclear chromatin was condensed,showing granular bright blue fluorescence;after 24 h of 20 μmol/L curcumin treatment,the cell body was shrunk,nuclear was condensed,chromatin was uneven,apoptotic bodies appeared,and even the nuclear fragmentation appeared;after 24 h of 40 μmol/L and 60 μmol/L curcumin treatment,the number of apoptotic cells was increased,a large number of nuclear fragmentation appeared.Conclusion Curcumin has a significant inhibitory effect on the proliferation of NPC cell line CNE-2,moreover promotes the apoptosis of CNE-2 cells.

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

Objective:To explore the feasibility of inguinal subcutaneous immunotherapy for allergic rhinitis ( AR ) in mice. Methods:36 female BALB/c mice were divided randomly into six groups( n=6 per group) including the control A,the model A, the treatment A groups,and the control B,the model B,the treatment B groups(inguinal subcutaneous immunotherapy for group A, cervical back subcutaneous immunotherapy for for group B). AR model was established with ovalbumin. At 25 to 55 days,ovalbumin im-munotherapy were performed in treatment groups,once two days,15 times totally. After intranasal rechallenge was performed at 56 to 62 days the AR symptom scores were documented. The eosinophils(EOS)in the nasal mucosa were measured by chromotropic acid 2R staining. Ovalbumin-specific IgE( OVA-sIgE) in the serum and expression of interferon-γ and interleukin-4 in the nasal lavage were measured by enzyme-linked immunosorbent assay meanwhile the ratio of interferon-γ and interleukin-4 was calc μlated. SPSS17. 0 software was used to analyze the data. Results:Before treatment ,the AR symptom scores of the model and treatment groups were more than 5. After treatment,the treatment A group were less than 5. The EOS count of the control A,model A,treatment A groups and the control B,model B, treatment B groups was 0. 78 ± 0. 31, 21. 60 ± 2. 90, 10. 43 ± 2. 56, 0. 83 ± 0. 46, 22. 44 ± 3. 39, 23. 40 ± 4. 24, respectively. The EOS count of the treatment A group was significantly lower than those in model A group ( P<0. 05 ) . There was no significant difference between treatment B and model B group ( P>0. 05 ) . OVA-sIgE expressed was negative in control groups and positive in other groups. The ratio of interferon-γ and interleukin-4 was 10. 75 ± 3. 38,10. 38 ± 3. 08,3. 02 ± 0. 69,2. 71 ± 0. 89,2. 52 ± 0. 30,5. 45±1. 41,respectively. The ratio in treatment A group was significantly higher than those in model A group(P<0. 05). There was no significant difference between treatment B and model B group ( P>0. 05 ) . Conclusion: Inguinal subcutaneous immunotherapy has a good effect on this disease. It spends short time ,has simple operation and good feasibility,which is a novel treatment method for AR in mice.

Objective To investigate the effects of simultaneous multi-level surgery for moderate to severe obstructive sleep apnea hypopnea syndrome (OSAHS). Methods A retrospective analysis was made on surgical cases of one hundred and thirty seven patients with moderate to severe OSAHS diagnosed by polysomnography (PSG). They were divided into multi-level group (n = 95) and UPPP group (n = 42). The two groups were compared in terms of postoperative complications as well as the related indicators of PSG , calgary sleep apnea quality of life index (SAQLI), epworth sleepiness scale (ESS), snore scales (SS) before operation and after operation. Results Just one patient in the multi-level group had difficulties in respiration and was rescued by timely tracheotomy. The AHI, LSaO2, TS90%, the total score and the scores on the four dimensions of SAQLI, ESS score, SS score in the multi-level group were significantly improved as compared both to the results after operation (P < 0.01) and to the UPPP group (P < 0.05). But only the AHI, LSaO2 and TS90% in the UPPP group were improved (P < 0.05). Conclusions The multi-level surgery is a safe and feasible therapy or moderate to severe OSAHS. The evaluation in subjective and objective ways can be more accurate in comprehensive reflecting the surgical efficacy and effects of OSAHS on patients′ of life quality.

OBJECTIVETo investigate the effect and explore its possible mechanisms of epidermal growth factor receptor(EGFR) expression in macrophages on the anti-cancer effect of berberine (BER) on the growth of colorectal cancer.

METHODSMice with EGFR gene defects in macrophages (Egfr(fl/fl) LysM-Cre) and with EGFR gene expression in macrophages (LysM-Cre) (control group) were treated with azoxymethane (AOM) to establish colorectal tumor models. These models were treated with or without berberine (BER) intervention. The number of colorectal tumors and the gut length in the two groups were measured. The proliferation of tumor cells was detected by Ki-67 immunohistochemistry and apoptosis was detected by annexin V-FITC fluorescence labeling. Western blot was used to detect the expression of cleaved-caspase-3 protein.

RESULTSAfter treated with AOM, the colorectal tumor number was 10.26 ± 1.43 in the LysM-Cre group and 7.62 ± 1.05 in the Egfr(fl/fl) LysM-Cre group, showing a significant difference (P = 0.021). The gut length was (6.04 ± 1.06) cm in the LysM-Cre group and (6.39 ± 0.92) cm in the gfrfl/flLysM-Cre group, with a non-significant difference between the two groups (P = 0.075). After treated with AOM plus BER intervention, the colorectal tumor number of the LysM-Cre group was 8.35 ± 1.22 and that in the Egfr(fl/fl) LysM-Cre group was 2.66 ± 0.38, showing a very significant difference between the two groups (P = 0.006). The gut length of the LysM-Cre group was (7.34 ± 1.16) cm and that of the Egfr(fl/fl) LysM-Cre group was (10.01 ± 1.72) cm (P = 0.028). After treated with AOM, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (78.31 ± 3.43)% and that in the Egfr(fl/fl) LysM-Cre group was (75.85 ± 2.92)% (P = 0.282). After AOM plus BER treatment, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (42.43 ± 3.09)% and that in the Egfr(fl/fl) LysM-Cre group was significantly lower (29.65 ± 2.47)% (P = 0.018). The ratio of annexin V-positive tumor cells was (0.95 ± 0.13)% in the LysM-Cre group, not significantly different from (1.13 ± 0.16)% in the Egfr(fl/fl) LysM-Cre group (P = 0.175). After AOM plus BER treatment, the ratio of annexin V-positive tumor cells in the LysM-Cre group was (32.10 ± 1.97)%, significantly lower than the (47.08 ± 2.83)% in the Egfr(fl/fl) LysM-Cre group (P = 0.010). The level of cleaved-caspase-3 protein expression was 235.92 ± 19.73 in the Egfr(fl/fl) LysM-Cre group, significantly higher than the 119.71 ± 12.87 in the LysM-Cre group (P = 0.012).

CONCLUSIONSThe growth of colorectal cancer cells in mice can be inhibited by BER treatment, and this anti-cancer effect of BER can be further enhanced by EGFR gene knockout in macrophages. The mechanisms may be related to the inhibition of proliferation and promotion of apoptosis in colorectal cancer cells.

Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; Berberine ; pharmacology ; therapeutic use ; Caspase 3 ; Colorectal Neoplasms ; drug therapy ; Genes, erbB-1 ; physiology ; Immunohistochemistry ; Macrophages ; metabolism ; Mice