ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Objective:To explore the changes in serum advanced receptor for glycation end-products (sRAGE) and neuregulin-1 (NRG-1) in patients with different conditions of H-type hypertension combined with acute ischemic stroke (AIS) and their relationship with short-term prognosis.Methods:A total of 185 patients with H-type hypertension complicated with AIS admitted to the Linyi Central Hospital from January 2020 to December 2022 were selected and included in the AIS group. According to the National Institutes of Health Stroke Scale (NIHSS) score, there were 55 cases in the mild group (≤4 points), 86 cases in the moderate group (5-20 points), and 44 cases in the severe group (>20 points); According to the improved Rankin scale score, the patients were divided into a poor prognosis group (>2 points) and a good prognosis group (≤2 points). Another 100 healthy individuals who underwent physical examinations during the same period in our hospital were selected as the control group. Enzyme linked immunosorbent assay was used to detect serum sRAGE and NRG-1 levels in subjects. The correlation between serum sRAGE, NRG-1 levels and NIHSS score in patients with H-type hypertension complicated with AIS was analyzed through Spearman test. A multivariate logistic regression model was used to analyze the influencing factors of poor short-term prognosis in patients with H-type hypertension complicated with AIS. The receiver operating characteristic (ROC) curve analysis revealed the predictive value of serum sRAGE and NRG-1 levels for poor short-term prognosis in patients with H-type hypertension complicated with AIS.Results:The serum sRAGE level in the AIS group was higher than that in the control group, while the NRG-1 level was lower than that in the control group (all P<0.05). The serum sRAGE levels of patients in the mild, moderate, and severe groups increased sequentially, while the NRG-1 levels decreased sequentially (all P<0.05). Spearman correlation analysis showed that the NIHSS score was positively correlated with serum sRAGE levels ( rs=0.847, P<0.001) and negatively correlated with serum NRG1 levels ( rs=-0.810, P<0.001) in patients with H-type hypertension and AIS. After 90 days of follow-up, the incidence of poor prognosis in 185 patients with H-type hypertension and AIS was 37.84%(70/185). Multivariate logistic regression model analysis showed that increased age, diabetes, increased NIHSS score, increased homocysteine (Hcy) and increased sRAGE were independent risk factors for poor short-term prognosis of patients with type H hypertension combined with AIS, while increased NRG-1 was an independent protective factor (all P<0.05). ROC curve analysis showed that the combined detection of serum sRAGE and NRG-1 levels predicted a poor short-term prognosis in patients with H-type hypertension and AIS, with an area under the curve (AUC) of 0.876, which was higher than the predicted values of 0.795 and 0.791 for serum sRAGE and NRG-1 levels alone (all P<0.05). Conclusions:Elevated serum sRAGE levels and decreased NRG-1 levels are closely related to worsening of the condition and poor short-term prognosis in patients with H-type hypertension and AIS. The combined detection of serum sRAGE and NRG-1 levels has high predictive value for poor short-term prognosis in patients with H-type hypertension and AIS.

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

Objective To evaluate the predictive value of CT-enhanced imaging-based radiomics nomogram for the status of microsatel-lite instability(MSI)in colon cancer.Methods A retrospective analysis was conducted on 129 postoperative colon cancer patients with confirmed MSI status.They were randomly divided into a training group(n=90)and a validation group(n=39)at a ratio of 7:3.Radiomics features were extracted from preoperative CT-enhanced images of the patients.The predictive performance of various machine learning algorithms was evaluated using the area under the curve(AUC).A nomogram model was developed by incorporating clinical independent risk factors,and the model's overall performance was assessed using decision curve analysis(DCA).Results Age and lesion site were identified as prominent independent risk factors and utilized in the construction of a clinical model.The light gradient boosting machine(LightGBM)algorithm was chosen for building a radiomics model.As a joint model,the AUC of the nomogram model of 0.917 in the training group and 0.822 in the validation group.The DCA confirmed the substantial clinical applicability of the nomogram model.Conclusion The CT-enhanced imaging-based radiomics nomogram offers a pioneering and individualized predic-tive approach for determining the MSI status in colon cancer.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

Objective:To conduct a scoping review of domestic and international guidelines on high-intensity physical activity, low-intensity physical activity, sedentary behavior, and sleep in adults, in order to understand the best combination of 24-hour activity and behavior for promoting adult health development, and to provide guidance for research in this field.Methods:Based on the scoping review guidelines of the Joanna Briggs Institute (JBI) of Australia as a methodological framework, we searched PubMed, Embase, Ovid, CINAHL, ClinicalKey, CNKI, Wanfang, MEDLINK Clinical Guidelines Network, UpToDate, BMJ Best Practice, International Guidelines Network, US National Guidelines Library, UK National Clinical Optimization Research Institute and Scotland Intercollegiate Guidelines Network. Guidelines that made recommendations for different intensity physical activities, sedentary behavior, and sleep in adults over a 24-hour period were included. The search time limit was from January 1, 2010, to August 31, 2022, and included literature was summarized and analyzed.Results:A total of 11 guidelines were included, of which only 2 guidelines from Canada and Saudi Arabia made specific time recommendations for 24-hour physical activity (frequency, intensity, type, and time) , sedentary time, and sleep in adults. The remaining 9 guidelines only made recommendations for adult physical activity and sedentary behavior, or only for physical activity.Conclusions:Future research should comprehensively measure the impact of the best time distribution of physical activity, sedentary behavior, and sleep on physical and mental health, and develop personalized guidelines on 24-hour activity suitable for the national conditions of China.

Objective:To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD).Methods:A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results:A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion:The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Esophageal Neoplasms/pathology* ; Carcinoma, Squamous Cell/pathology* ; Precancerous Conditions/pathology* ; Early Diagnosis

The aim of this study was to prepare tandem multimeric proteins of BmSPI38, a silkworm protease inhibitor, with better structural homogeneity, higher activity and stronger antifungal ability by protein engineering. The tandem multimeric proteins of BmSPI38 were prepared by prokaryotic expression technology. The effects of tandem multimerization on the structural homogeneity, inhibitory activity and antifungal ability of BmSPI38 were explored by in-gel activity staining of protease inhibitor, protease inhibition assays and fungal growth inhibition experiments. Activity staining showed that the tandem expression based on the peptide flexible linker greatly improved the structural homogeneity of BmSPI38 protein. Protease inhibition experiments showed that the tandem trimerization and tetramerization based on the linker improved the inhibitory ability of BmSPI38 to microbial proteases. Conidial germination assays showed that His₆-SPI38L-tetramer had stronger inhibition on conidial germination of Beauveria bassiana than that of His₆-SPI38-monomer. Fungal growth inhibition assay showed that the inhibitory ability of BmSPI38 against Saccharomyces cerevisiae and Candida albicans could be enhanced by tandem multimerization. The present study successfully achieved the heterologous active expression of the silkworm protease inhibitor BmSPI38 in Escherichia coli, and confirmed that the structural homogeneity and antifungal ability of BmSPI38 could be enhanced by tandem multimerization. This study provides important theoretical basis and new strategies for cultivating antifungal transgenic silkworm. Moreover, it may promote the exogenous production of BmSPI38 and its application in the medical field.
Animals ; Antifungal Agents/pharmacology* ; Escherichia coli/metabolism* ; Proteins/metabolism* ; Protease Inhibitors/chemistry* ; Bombyx/chemistry* ; Saccharomyces cerevisiae/metabolism* ; Peptide Hydrolases