Objective:To explore the correlation between high cholinergic pathway signaling and cognitive function in patients with Parkinson disease(PD) accompanied with sleep disorder.Methods:PD patients admitted from 2017 to 2022 were divided into PD with sleep disorder group (PD-SD group) ( n=56) and PD without sleep disorder group (PD-NSD group) ( n=41) according to the Parkinson's disease sleep scale (PDSS) score. All participants underwent magnetic resonance imaging examination.All patients were evaluated by the PDSS, Hoehn-Yahr (H-Y), Montreal cognitive assessment scale (MoCA), and cholinergic pathways hyper intensities scale (CHIPS). The difference of cognitive function between the two groups and the correlation between CHIPS and cognitive function were analyzed.Independent sample t-test, Spearman correlation analysis, and binary Logistic regression analysis were performed on the data by SPSS 26.0 statistical software. Results:(1)The MoCA score of the PD-SD group (22.00 (5.00)) was lower than that of the PD-NSD group (26.00 (5.00)) ( Z=-3.830, P<0.05). The total and all aspects scores of CHIPS in PD-SD group were higher than those in PD-NSD group(the total score of the low external capsule: 12.00(8.00), 0(8.00), the total score of the high external capsule: 12.00(2.00), 6.00(9.00), the total score of the radial crown: 8.00(0), 4.00(4.00), the total score of the centrum semiovale: 3.00(4.00), 0(2.00), the total score of the right side: 16.00(9.00), 5.00(10.00), the total score of the left side: 17.00(6.00), 7.00(9.00), the total score of CHIPS: 32.00(14.00), 14.00(20.00))( Z=-5.081, -5.873, -4.933, -3.211, -5.562, -6.232, -5.995, all P<0.05). (2)The correlation analysis between the score of CHIPS and cognitive function in the PD-SD group showed that, the total score of the low external capsule ( r=-0.286), the total score of the centrum semiovale ( r=-0.307), the total score of the right side ( r=-0.376), the total score of the left side ( r=-0.284) and the total score of CHIPS ( r=-0.349) were negatively correlated with MoCA(all P<0.05). (3)Binary Logistic regression analysis showed that white matter lesions in centrum semiovale, low inner capsule, right and left leukodystrophy were not influence factors for cognitive impairment (all P>0.05). Conclusion:PD patients with sleep disorders have lower cognitive function scores, higher CHIPS scores, and significant changes in white matter lesions compared to those without sleep disorders. In PD patients with sleep disorders, the higher the CHIPS score, the lower the cognitive function score, and the more significant the rate of cognitive impairment occurrence and development.

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b.Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases.It is involved in regulating the pathological process of myocardial infarction,myocardial ischemia/reperfusion injury,cardiac hypertrophy,atrial fibrillation,diabetic cardiomyopathy,atherosclerosis,pulmonary hyperten-sion,cerebral ischemia/reperfusion injury,Parkinson's disease,and Alzheimer's disease.Obviously,miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases.However,the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed.Therefore,in this review,we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases.Drugs targeting miR-135b for the treatment of diseases and related patents,highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases,have been discussed.

Objective:To evaluate the relationship between prognostic nutritional index (PNI) and myocardial injury after non-cardiac surgery (MINS).Methods:This was a retrospective cohort study. The clinical data of adult patients ( n=2 203) who underwent liver resection surgery with general anesthesia at our center from January 2016 to August 2019 were retrospectively collected. The predictive value of preoperative PNI for MINS and the optimal cut-off value of PNI were evaluated and determined according to the receiver operating characteristic curve, and the patients were divided into 2 groups based on the cut-off value: high PNI group and low PNI group. Logistic regression analyses were applied to investigate the relationship between preoperative PNI and MINS. According to the same inclusion and exclusion criteria, the clinical data of patients at our center from January 2022 to December 2023 were collected as the validation set ( n=2 525), and they were grouped using the same PNI cutoff value. Logistic regression analyses were used to verify the relationship between PNI and MINS. Results:The receiver operating characteristic curve analysis showed that the area under the curve of preoperative PNI for predicting MINS was 0.651 (95% confidence interval [ CI] 0.602-0.699), with an optimal cut-off value of 46.193, and the specificity and sensitivity were 0.729 and 0.519 respectively. The integer 46 was considered as the optimal cutoff value for PNI, and the patients were divided into low PNI group (PNI<46, n=606) and high PNI group (PNI≥46, n=1 597). Both univariate and multivariate logistic regression analyses showed that preoperative low PNI was an independent risk factor for the occurrence of MINS (univariate: OR=2.873, 95% CI 2.063-4.003, P<0.001; multivariate: OR=1.844, 95% CI 1.241-2.600, P=0.003). The results in the validation set were still robust (univariate: OR=2.694, 95% CI 1.890-3.833, P<0.001; multivariate: OR=1.602, 95% CI 1.071-2.385, P=0.021). Conclusions:Preoperative low-level PNI is an independent risk factor for MINS, with a certain predictive value.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.

The aim of this study was to produce recombinant porcine interferon gamma (rPoIFN-γ) by Chinese hamster ovarian (CHO) cells expression system and to analyze its antiviral activity. Firstly, we constructed the recombinant eukaryotic expression plasmid pcDNA3.1-PoIFN-γ and transfected into suspension cultured CHO cells for secretory expression of rPoIFN-γ. The rPoIFN-γ was purified by affinity chromatography and identified with SDS-PAGE and Western blotting. Subsequently, the cytotoxicity of rPoIFN-γ was analyzed by CCK-8 test, and the antiviral activity of rPoIFN-γ was evaluated using standard procedures in VSV/PK-15 (virus/cell) test system. Finally the anti-Seneca virus A (SVA) of rPoIFN-γ activity and the induction of interferon-stimulated genes (ISGs) and cytokines were also analyzed. The results showed that rPoIFN-γ could successfully expressed in the supernatant of CHO cells. CCK-8 assays indicated that rPoIFN-γ did not show cytotoxicity on IBRS-2 cells. The biological activity of rPoIFN-γ was 5.59×10⁷ U/mg in VSV/PK-15 system. Moreover, rPoIFN-γ could induced the expression of ISGs and cytokines, and significantly inhibited the replication of SVA. In conclusion, the high activity of rPoIFN-γ was successfully prepared by CHO cells expression system, which showed strong antiviral activity on SVA. This study may facilitate the investigation of rPoIFN-γ function and the development of novel genetically engineered antiviral drugs.
Swine ; Animals ; Cricetinae ; Interferon-gamma/pharmacology* ; Cricetulus ; CHO Cells ; Sincalide ; Recombinant Proteins/pharmacology* ; Antiviral Agents/pharmacology*

The aim of this study was to produce E^rns protein of bovine viral diarrhea virus (BVDV) by using suspensively cultured CHO cells expression system and to analyze the immunogenicity of the purified E^rns protein. In this study, the recombinant eukaryotic expression plasmid pcDNA3.1-BVDV-E^rns was constructed based on the gene sequence of BVDV-1 NADL strain. The E^rns protein was secreted and expressed in cells supernatant after transfecting the recombinant expression plasmid pcDNA3.1-BVDV-E^rns into CHO cells. The expression and purification of the E^rns protein was analyzed by SDS-PAGE, the reactivity was determined with anti-His monoclonal antibodies and BVDV positive serum with Western blotting. Immunogenicity analysis of the E^rns protein was determined after immunizing New Zealand white rabbits, and the serum antibodies were tested by indirect ELISA (iELISA) and indirect immunofluorescence (IFA). The serum neutralizing titer of the immunized rabbits was determined by virus neutralization test. The concentration of the purified E^rns protein was up to 0.886 mg/mL by BCA protein quantification kit. The results showed that the E^rns protein could be detected with anti-His monoclonal antibodies and anti-BVDV sera. Serum antibodies could be detected by iELISA on the 7th day post-prime immunization, and the antibody level was maintained at a high titer until the 28th day post-immunization. The antibody titer was 1:128 000. Furthermore, the expression of the E^rns protein in BVDV-infected MDBK cells could be detected with immunized rabbits sera by IFA. Moreover, antigen-specific neutralizing antibodies of 2.71 log₁₀ was induced in rabbits. In this study, purified BVDV E^rns protein was successfully produced using CHO suspension culture system, and the recombinant protein was proved to have a good immunogenicity, which may facilitate the development of BVD diagnosis method and novel subunit vaccine.
Rabbits ; Animals ; Cricetinae ; Cricetulus ; CHO Cells ; Antibodies, Viral ; Diarrhea Viruses, Bovine Viral/genetics* ; Antibodies, Monoclonal/genetics* ; Diarrhea ; Viral Vaccines/genetics*

Objective:To study the prevalence and distribution of adult thyroid diseases in urban and rural areas of Hebei Province.Methods:A multi-stage stratified cluster sampling method was used to select Renqiu City and Licun Town, Luquan City of Hebei Province as the urban and rural survey sites, respectively. Questionnaire survey, physical examination and thyroid B ultrasound examination were conducted on local permanent residents (≥ 5 years of residencies) over 18 years old. The fasting venous blood sample was collected to determine the serum thyroid function indicaters.Results:A total of 2 650 adults were surveyed, including 1 393 urban residents and 1 257 rural residents (1 357 males and 1 293 females). A total of 435 patients with thyroid diseases were diagnosed, the detection rate was 16.42%. There were seven thyroid diseases, including subclinical hypothyroidism (60.92%, 265/435), Hashimoto's thyroiditis (34.02%, 148/435), hypothyroidism (4.83%, 21/435), simple goiter (3.22%, 14/435), hyperthyroidism (2.53%, 11/435), subclinical hyperthyroidism (2.53%, 11/435), and thyroid cancer (1.84%, 8/435). The detection rates of thyroid diseases in urban and rural areas were 21.18% (295/1 393) and 11.14% (140/1 257), respectively. The detection rates of thyroid diseases in males and females were 11.42% (155/1 357) and 21.66% (280/1 293), respectively. The detection rates of thyroid diseases in 18-< 30, 30-< 40, 40-< 50, 50-< 60 and ≥60 years old were 13.46% (91/676), 14.81% (81/547), 15.42% (89/577), 20.94% (85/406) and 20.05% (89/444), respectively. There were statistically significant differences between different areas, gender and age groups (χ 2 = 48.54, 50.53, 14.68, P < 0.05). Conclusions:The detection rate of subclinical hypothyroidism in adults in urban and rural areas of Hebei Province is relatively high, followed by Hashimoto's thyroiditis. Attention should be paid to the screening, evaluation, and intervention of thyroid function among urban female populations.

Objective:To investigate the difference in the efficacy of extended trochanteric osteotomy (ETO) and subtrochanteric shortening osteotomy (SSO) in total hip arthroplasty (THA) for Crowe type IV developmental dysplasia of the hip (DDH).Methods:Forty patients (51 hips) who underwent primary THA for Crowe type IV DDH from April 2012 to August 2020 at the First Affiliated Hospital of Soochow University and the Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. The patients were classified into ETO (extended greater trochanteric osteotomy) group and SSO(subtrochanteric shortening osteotomy) group. There were 12 patients (14 hips) in the ETO group, with 3 males and 9 females, aged 49.9±16.7 years old (range, 22-75 years old) and 28 patients (37 hips) in the SSO group, with 7 males and 21 females, aged 50.3±14.0 years (range, 22-76 years). In both groups, Harris hip score (HHS), leg length discrepancy, limp, Trendelenburg sign were used to evaluate the functional results and anteroposterior radiographs of the pelvis were taken at each follow-up to assess bone healing at the osteotomy site, periprosthetic osteolysis, bone ingrowth and periprosthetic loosening. Complications were recorded and analyzed.Results:All 51 hips were followed up for at least 24 months. The operative time and total blood loss was 116.8±14.2 vs. 128.3±19.2 min and 650.8±191.4 vs. 808.3±151.3 ml in the ETO group and the SSO group with significant difference ( t=2.04, P=0.047; t=3.08, P=0.003) respectively. At the follow-up of 24 months the HHS of ETO and SSO groups were 94.8±6.3 vs. 93.9±4.9 points and the leg length discrepancy was 4.6±2.2 vs. 5.2±3.0 mm. The positive rate of Trendelenburg's sign was 7% vs. 16% and the incidence of limp was 17% vs. 29% in the ETO group and the SSO group with no significant difference ( t=0.54, P=0.591; t=0.68, P=0.499; P=0.657; P=0.693). The length of femoral shortening in the ETO group and SSO group was 30.8±4.1 vs 35.3±7.9 mm with significant difference ( t=2.02, P=0.049). Time for bone healing at the osteotomy site was 5.8±1.5 vs. 6.0±1.4 months and the incidence of intraoperative femoral fractures was 36% and vs. 65% with no significant difference ( t=0.45, P=0.657; χ 2=3.52, P=0.061). Bone in-growth (or bone on-growth) fixation was obtained for all acetabular and femoral prostheses, with no hips of prosthesis displacement, periprosthetic osteolysis, or dislocation. Conclusion:Total hip arthroplasty for Crowe type IV DDH can achieve satisfactory clinical efficacy with similar functional recovery and rate of complication in extended trochanteric osteotomy and subtrochanteric shortening osteotomy. However, the extended greater trochanter osteotomy can reduce the operation time, blood loss and length of femoral shortening.

Objective:To evaluate the effect of wrist-ankle acupuncture on the pharmacodynamics of remimazolam for loss of consciousness in the patients of different genders and ages undergoing painless gastroscopy.Methods:American Society of Anesthesiologists Physical Status classificationⅠor Ⅱ patients, undergoing elective painless gastroscopy, were divided into 4 groups according to gender and age: agedmale (age≥65 yr) group (group AM), agedfemale (age≥65 yr) group (group AF), young male (18 yr≤age <65 yr) group (group YM), and young female (18 yr≤age <65 yr) group (group YF). After 10 min of wrist-ankle acupuncture on 1st and 2nd areas of the bilateralupper limbs of the patient, modified Dixon′s up-and-down sequential experiment was used for the test.The initial dose of intravenous remimazolam was 0.20 mg/kg. Each time the dose increased/decreased by 0.05 mg/kg. If the patient lost consciousness, the next patient received a lower dose of remimazolam, otherwise a higher dose was given in the next patient. Loss of consciousness was defined as MOAA/S score was 0 or 1, and the process was repeated until 7 turning points appeared.The median effective dose (ED 50)and 95% confidence interval of remimazolam were calculated by probit method. Results:The ED 50 and 95% confidence interval of remimazolam were 0.296(0.233-0.376), 0.319(0.262-0.388), 0.323(0.278-0.375) and 0.344(0.285-0.415)mg/kg in AM, AF, YM and YF groups, respectively. There was no significant difference in ED 50 among the four groups ( P>0.05). Conclusions:Under the action of wrist-ankle acupuncture, the pharmacodynamics of remazolam is comparable when used for the patients of different genders and ages undergoing painless gastroscopy.

Objective:To summarize the application of pectoralis major flap in complex defects after maxillofacial " frozen neck" surgery.Methods:The clinical data of 7 patients with maxillofacial " frozen neck" admitted to the Department of Stomatology of the Xuzhou Central Hospital from October 2020 to October 2022 were retrospectively analyzed. The pectoralis major flap was used to repair the complex defects after surgery and the treatment effect was observed.Results:All 7 patients had survived flap transplantation with no serious complications. After 3 to 24 months of follow-up, the patients were basically satisfied with the treatment effect.Conclusions:The pectoralis major flap has reliable blood supply, abundant tissue, and can be applied flexibly with a high survival rate and significant repair effect. It is a good choice for repairing complex defects after " frozen neck" surgery, and it has clinical application value.