OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

Solid dispersion technology is an advanced technology to improve the solubility and bioavailability of poorly soluble drugs.Inhibition of the recrystallization and amorphous phase separation of amorphous solid dispersion (ASD) active pharmaceutical ingredients are important to ensure product stability,so the characterization of ASD phase separation is essential.Based on the principle of phase separation,this paper analyzed and summarized the advantages,disadvantages and applicability of the various characterization techniques,in order to provide an efficient reference for the characterization and stability study of ASD.

Objective To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids(PHSTF)for rheumatoid arthritis(RA).Methods Twenty-five male SD rats were randomly divided into normal control group,RA model group,PHSTF treatment(45 and 90 mg/kg)groups,and Tripterygium glycosides(TPG)tablet(10 mg/kg)group(n=5).Except for those in the normal control group,all the rats were subjected to collagen-induced arthritis(CIA)modeling using a secondary immunization method,after which PHSTF and TPG were administered via gavage once daily for 4 weeks.After the treatments,serum levels of TNF-α and IL-1β were measured using ELISA,and ankle joint pathologies were assessed with HE staining;the expression of citrullinated histone H3(Cit-H3),a neutrophil extracellular trap(NET)marker,in the ankle joints was evaluated with immunohistochemistry.In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester(PMA),the effects of PHSTF(100 and 200 μg/mL)on the expressions of Cit-H3,peptidylarginine deiminase 4(PADI4),neutrophil elastase(NE),and myeloperoxidase(MPO)were examined with Western blotting;immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.Results In the CIA rat models,PHSTF significantly alleviated ankle swelling,decreased serum levels of TNF-α and IL-1β,improved histopathological changes in the ankle joints,and reduced Cit-H3 expression in both the serum and ankle joint cartilage.In the isolated rat neutrophils,PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.Conclusion PHSTF can alleviate RA by inhibiting the formation of NETs.

Objective:To construct a multi-sequence MRI radiomics combined with KRAS mutation nomogram model to predict the efficacy of pathological complete response (pCR) in patients with rectal cancer after neoadjuvant chemoradiotherapy.Methods:This study was a case-control study. A total of 126 patients with rectal cancer who were treated with neoadjuvant chemoradiotherapy in the Second Affiliated Hospital of Harbin Medical University from June 2020 to December 2023 were retrospectively collected. The pathological response of the postoperative specimens was graded, with 64 cases of pCR and 62 cases of non-pCR. KRAS gene detection was performed on the pathological tissues before neoadjuvant chemoradiotherapy. Among the patients, 34 cases had KRAS mutants and 92 cases had KRAS wild-types. The 126 patients were randomly divided into a training set and a validation set at a ratio of 8∶2 by the random number method, with 101 and 25 cases, respectively. The difference in KRAS mutation status between the pCR group and the non-pCR group was compared by the χ2 test. The radiomic features were extracted from the baseline T 2WI, diffusion-weighted imaging, and apparent diffusion coefficient images of the patients. The optimal radiomic features were screened out to establish the radiomics model. The radiomics-KRAS joint model was constructed by logistic regression, and a nomogram was drawn. The application efficiency of the model was evaluated by the receiver operating characteristic curve and calibration curve. Results:There was a statistically significant difference in KRAS mutation between the pCR group and the non-pCR group in the training set ( χ2=4.69, P=0.032). Ten radiomics features were screened out in MRI images to establish the radiomics model. In the training set and validation set, the areas under the curve (AUC) of KRAS mutation, radiomics model and radiomics-KRAS nomogram model for evaluating pCR after neoadjuvant chemoradiotherapy were 0.665 (95% CI 0.592-0.757), 0.746 (95% CI 0.651-0.895) and 0.818 (95% CI 0.742-0.934), respectively, and the AUCs of the validation set were 0.613 (95% CI 0.582-0.755), 0.738 (95% CI 0.627-0.839) and 0.833 (95% CI 0.768-0.961), respectively. The results of DeLong test showed that the AUC of radiomics-KRAS nomogram model was higher than that of KRAS mutation and radiomics model, and the difference was statistically significant ( Z=0.58, 0.63, P=0.024, 0.022 in the training set; Z=0.54, 0.61, P=0.018, 0.035 in the validation set). The calibration curve showed that the predicted probability of the radiomics-KRAS nomogram model was consistent with the actual probability. Conclusions:The multi-sequence MRI radiomics combined with the KRAS mutation nomogram model has the best efficacy in predicting pCR in patients with rectal cancer after neoadjuvant chemoradiotherapy, and has good practical application value.

Objective To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids(PHSTF)for rheumatoid arthritis(RA).Methods Twenty-five male SD rats were randomly divided into normal control group,RA model group,PHSTF treatment(45 and 90 mg/kg)groups,and Tripterygium glycosides(TPG)tablet(10 mg/kg)group(n=5).Except for those in the normal control group,all the rats were subjected to collagen-induced arthritis(CIA)modeling using a secondary immunization method,after which PHSTF and TPG were administered via gavage once daily for 4 weeks.After the treatments,serum levels of TNF-α and IL-1β were measured using ELISA,and ankle joint pathologies were assessed with HE staining;the expression of citrullinated histone H3(Cit-H3),a neutrophil extracellular trap(NET)marker,in the ankle joints was evaluated with immunohistochemistry.In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester(PMA),the effects of PHSTF(100 and 200 μg/mL)on the expressions of Cit-H3,peptidylarginine deiminase 4(PADI4),neutrophil elastase(NE),and myeloperoxidase(MPO)were examined with Western blotting;immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.Results In the CIA rat models,PHSTF significantly alleviated ankle swelling,decreased serum levels of TNF-α and IL-1β,improved histopathological changes in the ankle joints,and reduced Cit-H3 expression in both the serum and ankle joint cartilage.In the isolated rat neutrophils,PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.Conclusion PHSTF can alleviate RA by inhibiting the formation of NETs.

OBJECTIVE To conduct the removal of K+ in traditional Chinese medicine decoction of Shenshuai Recipe by using the medicinal cation exchange resin(sodium polystyrene sulfonate). METHODS The concentration of K+ and Na+ in the decoction were determined by the ICP-MS method. And the UPLC method was established to determined the impact of K+ removal technique on indicative compounds in the decoction. After investigating the resin properties, static adsorption of cation exchange resin was applied in the study. It was preliminarily determined that the factors affecting K+ removal was temperature, resin amount and adsorption time. The single factor experiment was conducted to investigated the influence of these three factors on K+ adsorption in decoction. RESULTS The appropriate process conditions were determined as follows: the temperature was 25 ℃, the amount of resin was decoction︰resin (15 mL︰1 g), and the adsorption time was 1 min. The removal rate of K+ was > 80% in decoction of Shenshuai Recipe. The removal rate of K+ was 62.5%-80.3% in other decoction of renal disease prescription. This technology was greatly reduced the intake of K+through decoction in patients with renal failure. In addition, it was found that the adsorption effect of this medicinal resin on K+ was greatly affected by the ion environment, and this kind of resin was also selective for the adsorption of different indicative component. CONCLUSION The establishment of this process of K+ removal can well reduce K+ in the decoction of Shenshuai Recipe.

Water content determination is an important aspect of quality research in the whole process of pharmaceutical development, production, storage and use.Therefore, it is significant to develop an accurate and robust method for the determination of water content in the quality control of pharmaceuticals.In this article, the selection and strategy for the study of water determination methods are explained on the basis of general water determination principles and application examples in Chinese and foreign pharmacopoeias, together with the analysis of sample structure, solubility and water content.This article aims to provide basis for the development of moisture testing methods and formulation of proper quality standards for pharmaceuticals.

OBJECTIVE：To establish UPLC fin gerprint of 32 compatible herb pairs with Polygonum multiflorum as the core ， and to conduct multivariate statistical analysis. METHODS ：UPLC method was adopted. Using P. multiflorum and single decoction pieces of compatible herb as reference ，UPLC fingerprints of 32 compatible herb pairs of P. multiflorum were drawn. Common peaks were confirmed by relative retention time and UV absorption spectrum. Non-supervised PCA and supervised OPLS-DA were conducted by using SPSS 19.0 software and SIMCA 13.0 software. RESULTS ：There were totally 12 common peaks in UPLC fingerprints of 32 compatible herb pairs of P. multiflorum . The results of non-supervised PCA showed that the accumulative variance contribution rate of primary 6 principal components was 84.633％. The results of cluster analysis of PCA comprehensive score showed that single decoction piece of P. multiflorum ，compatible herb pairs of P. multiflorum with Lycium barbarum ，Rehmannia glutinosa，Paeonia lactiflora ，Codonopsis pilosula ，Eclipta prostrate ，Angelica sinensis ，Glycyrrhiza uralensis ，Astragalus membranaceus and Ophiopogon japonicus were clustered into one category ；others were clustered into one category. Results of supervised OPLS-DA analysis showed that eigen values of 4 principal components were 2.32，2.61，1.58 and 0.90，respectively. There were differences in the contents of 12 common components in the compatibility of P. multiflorum with tonic medicine and non-tonic medicine. The changes of the content of the components after compatibility with tonic medicine were similar. Common peak 7，4，6，3 were main reasons for the differences （variable importance projection value were all higher than 1）. CONCLUSIONS：Established fingerprint is simple in operation ，and can be combined with multivariate statistical analysis to evaluate the content changes of common components of 32 compatible herb pairs with P. multiflorum as the core.

Periampullary carcinoma includes carcinoma of head of pancreas, carcinoma of lower common bile duct, ampullary carcinoma and adenocarcinoma of duodenum. Most of the periampullary cancers shows the same clinical symptoms their imaging manifestations are overlapping or non-specific. Accurate qualitative positioning and staging of periampullary cancers are of great value in guiding of treatment plan and evaluate postoperative outcomes. CT and MRI examination have made progress in the diagnosis of periampullary carcinoma. CT scan has a good spatial and temporal resolution, while MRI has a good tissue resolution. CT and MRI examination can be used for preoperative assessment of tumor resectability and invasion range, which is of certain value.

Objective To investigate the characteristics of healthcare-associated infection(HAI) in elderly hospitalized patients,and analyze the risk factors for HAL Methods Incidences of HAI in elderly(elderly group) and non-elderly hospitalized patients (control) in a tertiary first-class hospital were investigated,the underlying diseases,infection sites,department distribution and so on between two groups of patients were compared.Results The incidence of HAI in elderly group was higher than that in control group(3.38 ％ vs 1.45 ％,P＜0.05);the proportions of hypertension and diabetes mellitus in elderly group was higher than control group,while cerebrovascular disease was lower than control group.The proportion of lower respiratory tract infection,urinary system infection and antimicrobial-associated diarrheal in the elderly were higher than control group(41.62％ vs 28.00％,15.44％ vs 12.02％,6.03％ vs 3.15％,respectively).The incidence of catheter-associated urinary tract infection in the elderly group was higher than that in control group(6.85‰ vs 3.95‰,RR95％CI =1.209-2.485,P＜0.05).The proportion of HAI in the elderly group in internal medicine departments was higher than that in control group (52.71％ vs 40.03％),while in intensive care unit was lower than control group (33.52％ vs 41.19％).Conclusion The characteristics of HAI in elderly patients are closely related to their demographic characteristics,early prevention of HAI in key sites should be carried out according to its characteristics.