ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Objective The objective of this study was to explore the values of hsa-let-7b-5p in the clinical diagnosis and targeted therapy of non-small cell lung cancer(NSCLC).Methods Thirteen pairs of NSCLC tissues and their adjacent tissues with the same pathological type in Harbin Medical University Cancer Hospital from September to October 2020 were collected,and differen-tially expressed miRNAs were obtained by RNA-Seq,and the expression of candidate miRNAs were verified in NSCLC tissues and cells through qRT-PCR.The effects of miRNAs on the proliferation,migration and invasion ability of NSCLC were verified by CCK-8 assay,clone formation assay,scratch assay and Transwell assay.Target genes were predicted using MiRDB,TarBase and ENCORI da-tabases,and gene enrichment analysis was performed using FunRich tool.Results Compared with adjacent tissues and human bron-chial epithelial cells(HBE),hsa-let-7b-5p was downregulated in NSCLC tissues and cell lines(A549 cells,H1299 cells,H358 cells and H460 cells)(P<0.05).The high expression of hsa-let-7b-5p inhibited the proliferation,migration and invasion ability of NSCLC(P<0.01).The results of target genes and enrichment analysis showed that among 378 target genes and related genes of hsa-let-7b-5p,147 genes were negatively correlated with the expression of hsa-let-7b-5p(P<0.05).Conclusion Hsa-let-7b-5phas inhibitory effects on the proliferation,migration and invasion of NSCLC.

ObjectiveTo investigate the effect of different doses of Jiedu Tongluo Shengjin prescription （JTSP） on serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and forkhead box P3 （FoxP3） in submandibular gland of NOD/Ltj mice with Sjögren's syndrome， and to explore the mechanism of JTSP on immune regulation in NOD/Ltj mice. MethodThirty NOD/Ltj mice （eight weeks old） were randomly divided into model group， JTSP low-dose group， JTSP medium-dose group， JTSP high-dose group and hydroxychloroquine group， and were administrated with normal saline， JTSP 9， 18， and 36 g·kg^-1， and hydroxychloroquine 60 mg·kg^-1 daily， respectively from the age of 12 weeks. Six ICR mice were given an equal amount of normal saline by gavage as the control group. During the experiment， daily water consumption and saliva secretion of mice at the age of 9， 12， 16 weeks were recorded. After 4 weeks of administration， submandibular gland and spleen tissues were dissected to calculate corresponding indexes. The pathological morphology of submandibular gland was observed by hematoxylin-eosin （HE） staining. Meso Scale Discovery （MSD） and immunohistochemistry were employed to detect the serum levels of IL-6， TNF-α and IL-10， and the expression and distribution of FoxP3 in submandibular gland， respectively. The protein expression of FoxP3 in mouse submandibular gland was determined by Western blot， and the mRNA expressions of FoxP3 and TNF-α were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the control group， the model group presented increased daily water consumption， decreased saliva secretion， lowered submandibular gland index， elevated pathological score of submandibular gland， up-regulated serum IL-6 and TNF-α and mRNA expression of TNF-α while down-regulated serum IL-10 and protein and mRNA expressions of FoxP3 in submandibular gland （P<0.05）. Compared with the conditions in model group， daily water consumption in JTSP groups was reduced while saliva secretion was increased， especially in medium-dose and high-dose groups （P<0.05）， and there was an increase in the submandibular gland index of JTSP medium-dose group （P<0.05） while a decrease in the spleen index of JTSP high-dose group （P<0.05）. Additionally， JTSP groups had lower pathological score of submandibular gland than the model group （P<0.05）， especially high-dose group， as well as lower serum IL-6 and TNF-α and mRNA expression of TNF-α while higher serum IL-10 （P<0.05）. JTSP at medium and high doses up-regulated the protein and mRNA expressions of FoxP3 in submandibular gland （P<0.05）. ConclusionJTSP may inhibit the secretion of inflammatory cytokines by regulating the stability of FoxP3⁺ regulatory T （Treg） cells， thus alleviating the systemic immune inflammation in Sjögren's syndrome.

Objective:To explore the clinical effect of cosmetic reconstruction for partial defect of distal segment of digits.Methods:Form January 2018 to January 2021, the Department of Hand Surgery of Institute for Hygiene of Ordnance Industry(The 521 Hospital of Weapon Industry) admitted 129 patients with partial defect of distal segment of thumb or fingers with phalange or tendon exposure. The patients were 111 males and 18 females with an average age of 34(17-59) years old. The sizes of nailbed defect were 0.4 cm×1.1 cm-1.8 cm×2.0 cm, the length of phalange defect was 0.4-1.8 cm, and the sizes of the soft tissue defect were 1.6 cm×1.8 cm-3.2 cm×4.8 cm. Great toe tissue flaps were used to reconstruct the partial defect of distal segment of thumb or fingers after debridement. Wounds of fibular flap of great toe in 77 cases were directly sutured in 17 patients. The donor sites in rest 60 great toes were narrowed first and then repaired with skin grafts in 10 cases, with artificial dermis in 28 cases and with transverse V-Y advancement flaps of ipsilateral great toes for 22 cases. Forty-nine of 52 donor site wounds for hallux toenail flap were repaired with artificial dermis and 3 with free peroneal artery perforator flaps. The method was outpatient follow-up. Postoperative follow-up lasted until July 2022. The check-items for follow-up included: occurrence of necrosis, appearance, shape and texture of the flap, appearance of the reconstructed nails, TPD of the reconstructed digit pulps, tolerance to cold on the scars of flaps, flexion and extension of the reconstructed digits. The healing time of phalanges of the reconstructed digits was evaluated by X-rays. The appearance, sensation, the tolerance to cold of great toe and the movement of donor foot were also assessed.Results:Postoperative follow-up lasted for 18 to 24 months, with an average of 21 months. A total of 128 flaps survived. Necrosis occurred in 1 fibular hallux flap, the necrosis was cured with a reverse digital proper artery island flap. Thereafter, all flaps healed well. The appearance, shape, texture and nails of reconstructed digits were close to the contralateral digits. The reconstructed thumb and finger were evaluated according to Zook, 127 cases were excellent and 2 cases were good.TPD of the pulps of the reconstructed digits was 4-10 mm. The mean score of the Vancouver scar scale(VSS) was 0.6 for scars of the reconstructed digits. The mean score of the Visual analog scale(VAS) was 0.3 for the tolerance to cold. Flexion and extension function recovered well in all the reconstructed digits. According to the Evaluation Criteria of Upper limb Function Hand Surgery Society of Chinese Medical Association, the function of hand was excellent in 127 cases and 1 in each of good and fair. X-rays of all digits showed the phalange healing of the reconstructed digits, with an average healing time of 2 months after surgery, without phalange resorption, infection, nonunion nor stress fracture. There was no difference between the length of the donor great toe and the contralateral toe, except the donor site of the great toe nail root. There was no significant visual difference between the appearance of the donor great toe and the contralateral toe. TPD of the pulps of donor great toe was 4-8 mm. The mean score of the VSS was 1.4 for scars in the donor great toe. The mean score of the VAS was 0.7 for the tolerance to cold of the donor great toe. There was no stress fracture at donor site, and the functions of donor foot were not affected when walking, running, jumping and tiptoeing in all patients.Conclusion:It is an ideal method for reconstructing a partial defect of distal segment of digit by great toe flap. It can not only reconstruct the partial defect of distal segment of the digit, but also results in a good appearance and satisfactory functions of the reconstructed digit. Damage to the donor site is minimum. The length of the donor great toe is unchanged, and it has little impact on sensation and appearance of the donor great toe. Meanwhile, there is no adverse effect on walking, running and jumping with the donor foot.

Objective To analyse the differential metabolites and related metabolic pathways in stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome by serum metabolomics.Methods This study observed 60 patients with stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome and 60 healthy volunteers in the same period.Liquid chromatography-mass spectrometry(LC-MS)was performed on the serum metabonomics.The differential metabolites were identified by multivariate statistical analysis of the original spectrogram and original data,and enrichment analysis of KEGG metabolic pathway was analyzed.Results A total of 60 patients in the group of stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome participated in the study,and a total of 60 healthy volunteers in the control group participated in the study.There was no statistical difference in general information and biochemical indicators between the two groups(P>0.05);Eighteen differential metabolites were found respectively,including phenylacetaldehyde,orthophosphate,guanosine,diethyl phosphate,2-dehydro-d-gluconate,guanine and 5-(2-hydroxyethyl)-4-methylthiazole down-regulated expression,taurocholate,2-propylglutaric acid,8-amino-7-oxononanoate,l-tyrosine,s-sulfo-l-cysteine,cyclohexanecarboxylic acid,porphobilinogen,(r)-acetoin,octanoylglucuronide,melatonin and solanine up-regulated expression,involving phenylalanine metabolism,thiamine metabolism,purine metabolism.Conclusion The differential metabolites reveal the metabolic essence of stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome from the micro level,and can provide clues for clinical early warning of patients with stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndromet.

Objective:To investigate the clinical effects of Masquelet technique with the transfer of free iliac inguinal flap in reconstruction of infectious bone and soft tissue defect after metacarpal fracture surgery.Methods:From January 2014 to January 2020, 16 patients suffered from infectious bone and soft tissue defect after surgery of metacarpal fracture were treated in Department of Hand Surgery, Institute for Hygiene of Ordnance Industry (Weapon Industry 521 Hospital). Debridement and vacuume sealing drainage (VSD) coverage of wound were carried out in emergency surgery, and Masquelet technique combined with free iliac inguinal flap for reconstruction of infected metacarpal bone defect were performed in sub-emergency surgery. The patients were 14 males and 2 females with an average age of 38 (20-50) years old. Plates were removed in 10 patients and retained in 6 patients. Defects of metacarpal bone ranged from 0.8 cm×0.8 cm×2.0 cm to 1.5 cm×2.0 cm× 5.1 cm in size. Soft tissue defects ranged from 3.6 cm×6.8 cm to 7.8 cm×11.6 cm. Tendon defects were found in all 16 patients. After the primary procedure of Masquelet technique combined with free iliac inguinal flap, routine anti-infection, anticoagulant, antispasmodic and other treatments were offered to all patients. Then all patients were observed by fortnightly reviews. After infection was cleared, the second phase of Masquelet treatment began. The defects of metacarpal bone were reconstructed with autologous cancellous bone grafts, and measures to prevent from infection together with other therapies were offered after the surgery. Follow-up of the second phase surgery was carried out once per 1-2 weeks and then per 2-4 months after bone union. The follow-up review items included: wound infection and necrosis, appearance, shape, texture and sensory recovery of flap. Bone union of infectious metacarpal defect was evaluated, recurrence of infection was closely observed as well as the resorption or nonunion of bone by X-rays. Hand function was assessed according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association. Donor sites healing and functional recovery were also included in the postoperative observation.Results:The follow-up time ranged from 1.5-3.0 (average 2.4) years. There was no necrosis of iliac inguinal flap, no recurrence of infection, and the flaps all healed well. The appearance, shape and texture of flaps were found close to the adjacent skin in all patients. Two-point discriminations (TPD) of the transferred iliac inguinal flaps were at 8-10 mm. X-ray reviews showed that bone union achieved in all patients. The time of bone union were 2.1-3.4 months (2.9 months in average) after bone grafting. There was no bone resorption, infection or nonunion. According to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 13 patients were excellent and 3 patients were good. All donor sites had primary healing with the motion of donor hips unaffected.Conclusion:Masquelet technique combined with free iliac inguinal flap is an effective, safe and feasible surgical procedure in reconstruction of infectious bone and soft tissue defect after metacarpal fracture surgery. It offers a satisfactory outcome with relatively less damage to the donor site.

Objective:To investigate DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumor (SLCT) and its associated clinicopathological features.Methods:Forty-three SLCTs and 40 other sex cord-stromal tumors (SCSTs) diagnosed between 2010 and 2017 at Fudan University Shanghai Cancer Center were examined for somatic DICER1 hotspot mutations by Sanger sequencing. The associations between mutation status and clinicopathological features, including patient age, tumor differentiation and recurrence, were analyzed.Results:Somatic DICER1 mutations were found in 51% (22/43) of SLCTs, while none in the other 40 SCSTs. The most common mutation of DICER1 was p.D1709N in exon 24 (41%, 9/22) and the second most common mutation of DICER1 was p.E1813K in exon 25 (14%, 3/22). A novel frameshift mutation (c.5464delG, p.M1837fs*16) was identified in one SLCT with microcystic pattern. Mutations were more likely to occur in patients under forty years of age ( P=0.046), whereas no significant associations were found between DICER1 mutations and clinical symptoms, morphology or tumor recurrence. Conclusions:Somatic DCIER1 hotspot mutations are specifically found in SLCT and may serve as an ancillary marker in differential diagnosis of SLCT from other SCST. The mutations occur more often in young patients (<40 years old). Additional studies are warranted to examine the associations between DICER1 mutations and clinicopathological features and prognosis of SLCT.

Methods for achieving diagnosis of Parkinson's disease (PD) based on speech data mining have been proven effective in recent years. However, due to factors such as the degree of disease of the data collection subjects and the collection equipment and environment, there are different categories of sample aliasing in the sample space of the acquired data set. Samples in the aliased area are difficult to be identified effectively, which seriously affects the classification accuracy of the algorithm. In order to solve this problem, a partition bagging ensemble learning is proposed in this article, which measures the aliasing degree of the sample by designing the the ratio of sample centroid distance metrics and divides the training set into multiple subsets. And then the method of transfer training of misclassified samples is used to adjust the results of subset partitioning. Finally, the optimized weights of each sub-classifier are used to integrate the test results. The experimental results show that the classification accuracy of the proposed method is significantly improved on two public datasets and the increasement of mean accuracy is up to 25.44%. This method not only effectively improves the classification accuracy of PD speech dataset, but also increases the sample utilization rate, providing a new idea for the diagnosis of PD.
Algorithms ; Data Mining ; Humans ; Machine Learning ; Parkinson Disease ; diagnosis ; Speech

Objective To observe the pathological changes of brain tissues in the WHBE rabbit model of sporadic Alzheimer disease (AD). Methods Thirty 3 -4-month old male WHBE rabbits were randomly divided into 3 groups:normal control (NC) group, high cholesterol diet (HCD) group, high cholesterol diet + copper drinking water ( HCD+ Cu2+) group, 10 in each group. Another 10 senile (36-48-month old) male WHBE rabbits were taken as senile group. The NC group and the senile group were fed a normal basic diet, the HCD group fed a 2% cholesterol diet, and the HCD+Cu2+group fed a 2% cholesterol diet plus 0. 12 PPM copper drinking water for 12 weeks. The levels of total cholesterol (TC) and β-amyloid protein (Aβ) 1-42 were measured at 12 weeks. The activity of superoxide dismutase ( SOD) and the content of malondialdehyde (MDA) in the cortex and the hippocampus were detected. In addition, the covered area of Aβ, β-site APP cleaving enzyme 1(BACE1) and phosphorylated tau (p-tau) protein in coronal sections of brain tissues were also observed by immunohistochemical staining. The senile plaques and the neurofibrillary tangles were observed by Congo red and Bielschowsky staining, respectively. Results The body weight of WHBE rabbits in the senile group was significantly higher than that of the NC group ( P ＜ 0. 01 ), and the plasma TC and Aβ1 -42 in each group were significantly higher than that in the NC group (P ＜ 0.05, P ＜ 0.01). The activity of SOD in brain tissues was significantly lower than that of NC group (P＜ 0. 05), and the MDA content was significantly higher than that of NC group (P＜ 0. 05, P ＜ 0. 01). Immunohistochemical staining showed that the covered area of Aβ, BACE1 and p-tau in brain tissues of all groups were significantly higher than that of NC group (P ＜ 0. 05, P ＜ 0. 01), and the covered area of BACE1 and p-tau protein in the brain tissues of HCD + Cu2+group was also significantly higher than that of the HCD group (P ＜ 0. 05, P ＜ 0. 01). Congo red and Bielschowsky staining showed that the number of senile plaques and neurofibrillary tangles were observed in the brain tissues of the HCD, HCD+Cu2+and senile groups. Conclusions High cholesterol diet or supplemented with trace copper drinking water can induce obvious AD pathological changes in WHBE rabbit models of sporadic AD with obvious oxidative damage, increased Aβ deposition and senile plaque in the brain, and pathological changes of tau. WHBE rabbit can be used in the study of animal models of neurodegenerative diseases.

Diagnosis of Parkinson's disease (PD) based on speech data has been proved to be an effective way in recent years. However, current researches just care about the feature extraction and classifier design, and do not consider the instance selection. Former research by authors showed that the instance selection can lead to improvement on classification accuracy. However, no attention is paid on the relationship between speech sample and feature until now. Therefore, a new diagnosis algorithm of PD is proposed in this paper by simultaneously selecting speech sample and feature based on relevant feature weighting algorithm and multiple kernel method, so as to find their synergy effects, thereby improving classification accuracy. Experimental results showed that this proposed algorithm obtained apparent improvement on classification accuracy. It can obtain mean classification accuracy of 82.5%, which was 30.5% higher than the relevant algorithm. Besides, the proposed algorithm detected the synergy effects of speech sample and feature, which is valuable for speech marker extraction.