ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

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.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

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.

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 explore the mechanism of electroacupuncture (EA) at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) on learning and memory impairment in vascular dementia (VD) rats by observing the influences on the N-methyl-D-aspartate receptor (NMDAR)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway and the excitotoxicity induced by hippocampal calcium overload. METHODS: Thirty-two male SD rats of SPF grade were selected and randomized into a normal group (6 rats), a sham-operation group (6 rats) and an operation group (20 rats). VD model was established with the modified Pulsinelli's four-vessel occlusion (4-VO) method. Twelve rats after successfully modeled were assigned randomly into a model group and an EA group, 6 rats in each one. In the EA group, EA was delivered at bilateral "Fengchi" (GB 20) and "Sishencong" (EX-HN 1), with the continuous wave, the frequency of 2 Hz and the electric current of 1 mA. Stimulation intensity was adjusted depending on the slightly trembling of rat head. EA was given once daily, 30 min each time; and EA intervention was delivered for 21 days continuously. Using Morris water maze test, the learning and memory function was assessed. The neuronal morphology in the hippocampal CA1 was observed with HE staining; the level of glutamate (GLU) in serum and hippocampal tissue, as well as the activity of calcium pump (Ca²⁺-ATP) in the hippocampus were detected using colorimetric method. The protein expression of NMDAR, calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), phosphorylated calmodulin-dependent protein kinase Ⅱ (p-CaMKⅡ), phosphorylated cyclic phosphoradenosine effector element binding proteins (p-CREB), CREB, and BDNF in the hippocampal CA1 was detected using immunohistochemistry. The protein expression of NMDAR, CREB, p-CREB and BDNF in the hippocampal tissue was detected using Western blot method. RESULTS: Compared to the sham-operation group, in the model group, the escape latency was prolonged and the platform crossing times of rats were reduced (P<0.01), the hippocampal neuron structure was damaged to different degrees, the structure in hippocampal CA1 was loosened, the arrangement disorganized, with clear grid-like structure; the neuronal morphology was irregular, pyknosis and even dissolution occurred, glial cells increased, blood capillary was dilated and the inflammatory cells were infiltrated and scattered. The level of GLU in the serum and hippocampal tissue and the protein expression of hippocampal NMDAR were elevated (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were reduced (P<0.01, P<0.05); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB were dropped (P<0.05). In comparison with the model group, in the EA group, the escape latency was shortened and the platform crossing times of rats rose (P<0.01), the arrangement was improved in the hippocampal CA1, the neuronal morphology was intact, the nucleoli were clear relatively and the pyknosis or dissolution were attenuated, the numbers of glial cells reduced relatively, the dilation of blood capillary was alleviated. The level of GLU in the serum and hippocampal tissue and the protein expression of NMDAR were reduced in the hippocampal tissue (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were elevated (P<0.05, P<0.01); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB increased (P<0.05). CONCLUSION EA at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) can attenuate learning and memory impairment in VD rats, which may be obtained by reducing GLU level in hippocampal tissue, inhibiting hippocampal excitotoxicity, mediating protein expression related to the NMDAR/CREB/BDNF signaling pathway, and maintaining neuronal survival and growth.
Electroacupuncture ; Male ; Animals ; Rats, Sprague-Dawley ; Learning ; Memory ; Signal Transduction ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Memory Disorders/therapy* ; Brain-Derived Neurotrophic Factor/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Dementia, Vascular/therapy*

OBJECTIVE: To investigate the incidence of perioperative deep venous thrombosis (DVT) of lower extremities and its risk factors in elderly patients with femoral neck fracture. METHODS: The clinical data of 4 109 elderly patients with femoral neck fracture admitted between August 2012 and November 2020 and met the selection criteria were retrospectively analyzed. Among them, there were 1 137 males and 2 972 females; their ages ranged from 65 to 101 years, with an average of 77.0 years. The time from fracture to admission ranged from 1 to 360 hours, with an average of 35.2 hours. There were 1 858 cases of hemiarthroplasty, 1 617 cases of total hip arthroplasty, and 634 cases of internal fixation surgery. The preoperative age-adjusted Charlson comorbidity index (aCCI) was 4 (3, 5). Perioperative DVT occurred in 857 cases (20.9%). Univariate analysis was performed on age, gender, body mass index, fracture side, time from fracture to admission, operation type, anesthesia type, blood transfusion, blood pressure after admission, and preoperative aCCI in patients with and without perioperative DVT, and logistic regression analysis was used to screen the risk factors of perioperative DVT in elderly patients with femoral neck fracture. RESULTS: Univariate analysis showed that there were significant differences in age, gender, time from fracture to admission, operation type, and preoperative aCCI between the two groups ( P<0.05). Further logistic regression analysis showed that age>75 years, female patients, time from fracture to admission>24 hours, and preoperative aCCI>5 were risk factors for perioperative DVT ( P<0.05). CONCLUSION Elderly patients with femoral neck fracture have a higher incidence of perioperative DVT. The advanced aged and female patients, patients with longer fracture time and more comorbidities need to pay special attention to the prevention of perioperative DVT to minimize the occurrence of DVT during femoral neck fractures.
Humans ; Femoral Neck Fractures/complications* ; Female ; Male ; Aged ; Venous Thrombosis/epidemiology* ; Risk Factors ; Aged, 80 and over ; Retrospective Studies ; Lower Extremity/blood supply* ; Arthroplasty, Replacement, Hip/adverse effects* ; Incidence ; Fracture Fixation, Internal/methods* ; Postoperative Complications/etiology* ; Perioperative Period ; Logistic Models ; Hemiarthroplasty/adverse effects*

【Objective】 To investigate the effect of immunoglobulin G (IgG) dimer concentration of intravenous immunoglobulin (IVIG) on the binding ability of IgG Fc fragment to THP-1 cell surface receptors. 【Methods】 Firstly, protein purification and high performance liquid chromatography (HPLC) were used to prepare different concentrations of IgG dimers. After that, IgG dimer was added to IVIG to prepare IVIG containing different concentrations of IgG dimer. Finally, based on the method established in our laboratory, we analyzed the effect of IgG dimer concentration in IVIG on the binding ability of IgG Fc fragment to THP-1 cell surface receptors. 【Results】 When the concentration of IgG dimer in IVIG was 1.11%-10.30%, its binding ability to Fc receptors on the surface of THP-1 cell was 97.67%-135.33%, and this binding ability was positively correlated with the concentration of IgG dimer. When the IgG dimer concentration exceeded 13.22%, the binding ability had no correlation with the IgG dimer concentration. 【Conclusion】 A certain concentration of IgG dimer can promote the binding ability of the IgG Fc fragment in IVIG to receptors on the surface of THP-1 cells, which needs further verification from animal experiments and clinical data.

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.