Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.

Objective:To investigate the diagnosis of dual-energy X-ray absorptiometry(DXA)for osteoporosis(OP)of postmenopausal patients with rheumatoid arthritis(RA)in Qinghai region and the risk factors of them.Methods:A total of 200 postmenopausal female RA patients who admitted to Qinghai Hospital of Traditional Chinese Medicine from May 2022 to April 2023 were selected.All patients were tested for bone mineral density(BMD)after admission,and lumbar spines L1-L4,whole lumbar,large trochanter,Ward's triangle area,whole body and whole forearm were measured by DXA.According to the results of BMD test,patients whose BMD T values of all body parts-2.5 SD were less or equal to-2.5 were included in the OP group(121 cases),and patients whose BMD T value of all body parts were larger than-2.5 SD were included in the non-OP group(79 cases).The BMD T value of different body parts between two groups of RA patients were compared and analyzed.The area under curve(AUC)of receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficiency of BMD T value for OP.The logistic regression method was adopted to analyze the risk factors that postmenopausal RA patients of Qinghai region occurred OP.Results:The BMD T values of L1,L2,L3,L4,whole lumbar,large trochanter,Ward's triangular area,whole body and whole forearm of OP group were obviously lower than those of the non-OP group.In analysis of ROC curve,the sensitivities of BMD T values of L1,L2,L3,L4,whole lumbar,large trochanter,Ward's triangle area,whole body and forearm were respectively 96.20%,95.22%,90.16%,96.03%,92.01%,89.36%,99.26%,90.02% and 96.03% in diagnosing OP,and the specificities of them were respectively 81.00%,82.19%,85.22%,83.06%,83.06%,90.22%,80.06%,86.23%,83.09%,and the AUC values of them were respectively 0.908,0.905,0.896,0.906,0.903,0.879,0.918,0.901 and 0.906.The results of the logistic-regression analysis showed that advanced age,long disease course,rheumatic activity scores of 28 joints,erythrocyte sedimentation rate and Calcium supplementation were the risk factors of occurring OP in postmenopausal RA patients in Qinghai region.Conclusion:The DXA method that detects BMD of RA patients who occur OP can be used as gold standard to assess OP,and there are many risk factors that affect the occurrence of OP in postmenopausal RA patients of Qinghai region.The clinical work should combine with relative factors to formulate reasonable measure so as to reduce the incidence of OP.

Objective To investigate the effect of multi-sided foramen ultrafine drainage tube with metal support on the formation of thoracic residual cavity after uniportal video-assisted thoracoscopic (VATS) upper lobectomy. Methods The clinical data of the patients who underwent uniportal VATS upper lobectomy for lung cancer in the Department of Thoracic Surgery of the First Hospital of Lanzhou University from January 2021 to April 2022 were retrospectively analyzed. According to the type of ultrafine drainage tube used in the surgery, the patients were divided into a test group (using metal-supported multi-sided foramen ultrafine drainage tube) and a control group (using ordinary 12F ultrafine drainage tube). The incidence of postoperative thoracic residual cavity and operation-related data were compared between the two groups. Results A total of 200 patients were enrolled, including 126 males and 74 females, with a mean age of 57.52 years. There were 90 patients in the test group, and 110 patients in the control group. The incidence of postoperative thoracic residual cavity in the test group was lower than that in the control group (P=0.045). The differences in the postoperative bedtime, postoperative visual analogue scale, postoperative analgesic pump using time, postoperative hospitalization time, times of postoperative thoracentration and drainage, postoperative drainage time and hospitalization cost between the two groups were statistically significant (P<0.05). The incidences of postoperative lung infection, pleural effusion and atelectasis complications were lower in the test group than those in the control group (P<0.05). The differences in the preoperative anesthesia time, operation time, intraoperative bleeding and postoperative lung leakage were not statistically significant (P>0.05). Conclusion The use of multi-sided foramen ultrafine drainage tube with metal support can reduce the incidence of thoracic residual cavity after uniportal VATS upper lobectomy, and can reduce pain and economical burdens and the incidence of operation-related complications, accelerating the recovery of patients after surgery. The application of multi-sided foramen ultrafine drainage tube with metal support in uniportal VATS upper lobectomy can be widely used in the clinic.

Objective To investigate the clinical effect of metal supported multi-sided versus ordinary ultra-fine drainage tube in the uniportal video-assisted thoracic surgery (VATS) lower pulmonary lobectomy. Methods From January 2021 to June 2022, the clinical data of patients who underwent uniportal VATS lower lobectomy in our hospital were retrospectively analyzed. According to the different types of ultra-fine drainage tubes used in the surgery, the patients were divided into an experimental group (using multi-sided hole 10F ultra-fine drainage tubes with metal support) and a control group (using ordinary 12F ultra-fine drainage tubes). The clinical data of the two groups were compared. Results A total of 190 patients were enrolled, including 108 males and 82 females. There were 90 patients in the experimental group aged 56.60±10.14 years; and 100 patients in the control group aged 57.07±11.04 years. The incidences of postoperative lung infection and pleural effusion in the experimental group were lower than those in the control group, with statistically significant differences (P<0.05). The postoperative visual analogue scale score, the need to adjust the chest drainage tube after the surgery, the need for chest puncture after the surgery, the time of postoperative chest tube removal, and the hospitalization cost were statistically different (P<0.05). There was no statistical difference in the length of postoperative hospital stay or the incidences of postoperative lung leakage, arrhythmia, and atelectasis complications (P>0.05). Conclusion Compared with the ordinary ultra-fine drainage tubes, multi-sided hole ultra-fine drainage tubes with metal support can reduce the incidences of lung infection and pleural effusion complications after the uniportal VATS lower lobectomy, reduce the pain and economic burden, which can be applied in the uniportal VATS lower lobectomy.

Objective To explore the antimicrobial resistance of carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from blood and the related risk factors for infection in patients.Methods Clinical data of 383 KP-infected patients from whose blood Klebsiella pneumoniae(KP)were isolated during hospitalization period in a hos-pital from January 2018 to December 2021 were retrospectively analyzed.Patients were divided into CRKP group(n=114)and non-CRKP group(n=269)based on antimicrobial resistance.According to the prognosis,114 patients in the CRKP group were subdivided into the death group(n=30)and the survival group(n=84).General informa-tion,underlying diseases,antimicrobial use,and infection outcomes of two groups of patients were compared,and risk factors for infection and death after infection were analyzed.Results The resistance rates of KP to tigecycline and compound sulfamethoxazole showed upward trends,with statistically significant differences(both P=0.008).The CRKP group had higher resistance rates to amikacin,aztreonam,compound sulfamethoxazole,ciprofloxacin,cefepime,cefoperazone/sulbactam,piperacillin/tazobactam,tigecycline,ceftazidime,tobramycin,and levofloxacin,as well as higher in-hospital mortality than the non-CRKP group,with statistically significant differences(all P＜0.05).Acute pancreatitis prior to infection(OR=16.564,P＜0.001),hypoalbuminemia(OR=8.588,P＜0.001),stay in in-tensive care unit prior to infection(OR=2.733,P=0.017),blood transfusion(OR=3.968,P=0.001),broncho-scopy(OR=5.194,P=0.014),surgery within 30 days prior to infection(OR=2.603,P=0.010),and treatment with carbapenems(OR=2.663,P=0.011)were independent risk factors for the development of CRKP blood-stream infection(BSI).Cardiac insufficiency before infection(OR=11.094,P=0.001),combined with pulmonary infection(OR=20.801,P=0.010),septic shock(OR=9.783,P=0.002),disturbance of consciousness(OR=11.648,P=0.001),and receiving glucocorticoid treatment(OR=5.333,P=0.018)were independent risk factors for mortality in patients with CRKP BSI.Conclusion The resistance rate of KP from BSI to tigecycline and com-pound sulfamethoxazole presents upward trend.Underlying diseases,invasive procedures,and carbapenem treat-ment are closely related to CRKP BSI.Cardiac insufficiency,pulmonary infection,septic shock,disturbance of con-sciousness,and glucocorticoid treatment can lead to death of patients with CRKP BSI.

Objective To study the efficacy of bronchoalveolar lavage(BAL)combined with prone positioning in children with Mycoplasma pneumoniae pneumonia(MPP)and atelectasis and its effect on pulmonary function.Methods A prospective study was conducted on 94 children with MPP and atelectasis who were hospitalized in Ordos Central Hospital of Inner Mongolia from November 2020 to May 2023.The children were randomly divided into a treatment group and a control group,with 47 children in each group.The children in the treatment group were given conventional treatment,BAL,and prone positioning,and those in the control group were given conventional treatment and BAL.The two groups were compared in terms of fever,pulmonary signs,length of hospital stay,lung recruitment,and improvement in pulmonary function.Results Compared with the control group,the treatment group had significantly shorter time to improvement in pulmonary signs and length of hospital stay and a significantly higher rate of lung recruitment on day 7 of hospitalization,on the day of discharge,and at 1 week after discharge(P<0.05).Compared with the control group,the treatment group had significantly higher levels of forced vital capacity(FVC)as a percentage of the predicted value,forced expiratory volume(FEV)in 1 second as a percentage of the predicted value,ratio of FEV in 1 second to FVC,forced expiratory flow at 50%of FVC as a percentage of the predicted value,forced expiratory flow at 75%of FVC as a percentage of the predicted value,and maximal mid-expiratory flow as a percentage of the predicted value on the day of discharge and at 1 week after discharge(P<0.05).There was no significant difference in the time for body temperature to return to normal between the two groups(P>0.05).Conclusions In the treatment of children with MPP and atelectasis,BAL combined with prone positioning can help to shorten the time to improvement in pulmonary signs and the length of hospital stay and promote lung recruitment and improvement in pulmonary function.

Objective:To investigate the preparation of sustained-release microspheres of brain-derived neurotrophic factor (BDNF) and its repairing effects on hypoxic-ischemic brain damage as well as the regulation of the tyrosine receptor kinase B (TrkB)/cAMP-response element binding protein (CREB) pathway in rats.Methods:BDNF sustained-release microspheres were prepared by emulsification-solvent evaporation method and polymer alloying method. The morphology of the microspheres was observed by a transmission electron microscope. The particle size and Zeta potential of the microspheres were measured by a Malvern ZS90 particle size analyzer, and the encapsulation rate and plasmid loading of the BDNF sustained-release microspheres were determined. The sustained release of the microspheres in vitro was also detected. A total of 45 SD rats were randomly divided into the sham-operation group, the model group, and the treatment group, with 15 rats in each group. Except for the sham-operation group, ischemic-hypoxic brain injury models were established in the other two groups by ligating the right common carotid artery and in a hypoxia environment. The rats in the treatment group were injected with 100 mg/kg of BNDF sustained-release microsphere solution via the tail vein once a day for 4 weeks, while the rats in the sham-operation group and the model group were injected with an equal amount of blank microsphere solution via the tail vein. At the end of the intervention, the neurological function scores, brain tissue water content, cerebral infarction area, malondialdehyde (MDA), and superoxide dismutase (SOD) levels were measured. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA). The protein expressions of BDNF, TrkB, and phosphorylated CREB (p-CREB) were detected by Western Blot. Results:The appearance of BDNF sustained-release microspheres was round or oval, with a smooth surface and uniform size distribution. No interfused microspheres were observed. The size of microspheres was (221.49 ± 5.75) nm, the Zeta potential was (?27.03 ± 4.22) mV, and the encapsulation rate was (80 ± 2) %. The microspheres (1 mg) could carry (1.55 ± 0.04) μg of BDNF plasmid, and the sustained release of the drug stabilized at day 28. Compared with the model group, the neurological function score, brain tissue water content, cerebral infarction area, MDA, TNF-α, and IL-6 levels were decreased, and the SOD level and the protein expression of BDNF, TrkB, and p-CREB were increased in the treatment group (all P < 0.05). Conclusions:BDNF sustained-release microspheres can promote the repair of neurological damage caused by cerebral ischemia and hypoxia, reduce inflammation response and oxidative stress, and alleviate cerebral edema and cerebral infarction, which may play a role by activating the BDNF/TrkB/CREB pathway.

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

Objective:To investigate the effects and potential mechanisms of galectin-3(Gal3)on mast cells activation and skin injury in a psoriatic murine model.Methods:Imiquimod was applied to the bare skin on back of SPF(Gal3+/+)mice and their matched(Gal3-/-)siblings respectively once daily for 5 d to establish a psoriatic mice model.The development and dynamics of skin le-sions were monitored and recorded,scored.with the psoriasis area and severity index(PASI).The expressions of il-1 and il-17 in the damaged skin were detected by real-time PCR to compare the severity of inflammation between Gal3+/+ mice and their Gal3-/-siblings.HE staining was used to observe the histopathological changes of skin.The difference in morphology and distribution of mast cells were examined by toluidine blue staining.Immunohistochemistry and image analysis techniques were improved to assay the expression and distribution of activated mast cells markers such as tryptase and 5-hydroxytryptamine(5-HT).Results:The typical psoriatic signs in-cluding erythema,scaling and infiltration were formed in mice after continuous administration of imiquimod in Gal3-/-mice,whereas Gal3+/+ mice just developed small scaling and mild infiltration.PASI score of Gal3-/-mice was significantly higher than that of Gal3+/+mice.In accordance,il-1 and il-17 were increased in the skin lesions of Gal3+/+ mice and Gal3-/-mice,but these inflammatory factors were more upregulated remarkably in the latter.Histopathology observation revealed that the epidermis of Gal3+/+ mice was slightly thickened,whereas thickened epidermis of Gal3-/-mice was more seriously and the rete ridges extended downward,with massive in-flammatory cells aggregation.Toluidine blue staining indicated that the mast cells were sparsely distributed and most of their structures were intact in Gal3+/+ mice,instead the mast cells of Gal3-/-mice were mostly in degranulation state with increased and distributed widely in skin.Immunohistochemistry staining revealed that tryptase and 5-HT,compared with those of Gal3+/+ mice,were increased obviously in the lesioned skin of Gal3-/-mice,most of them were concentrated in the epidermal in particular.Conclusion:The defi-ciency of Gal3 may result in over-activation and degranulation of mast cells at the skin in psoriatic mice model,which aggravates the occurrence of dermatitis inflammatory injury and disease progression in psoriasis,and Gal3 plays suppressive effects on mast cells acti-vation and degranulation at the skin lesions in this model.