To investigate the mechanism of Qitu Erzhi Decoction(QTEZ) in ameliorating chemotherapy-induced myelosuppression and the focus of its decomposed formulae on the effects of hematopoietic cells of the three lineages, respectively. Ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of QTEZ intestinal absorption liquid and obtain the target sites, which were intersected with chemotherapy-induced myelosuppression targets collected from several databases, including OMIM, and an interaction network was established based on network pharmacology for Gene Ontology(GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Hematopoietic stem cells of mice were taken after intraperitoneal injection of 5-fluorouracil for myelosuppression modeling and randomly divided into the model group, Qitu Erzhi group, Astragali Radix-Angelicae Sinensis Radix group, Ligustri Lucidi Fructus-Ecliptae Herba group, Psoraleae Fructus-Cuscutae Semen group, and positive drug group, which were given the corresponding traditional Chinese medicine intestinal absorption liquid and the positive drug granulocyte colony-stimulating factor, respectively. The normal hematopoietic stem cells were taken as the control group and were given the intervention of normal saline. The proliferation of hematopoietic progenitor cells of three lineages was observed by flow cytometry, and the cell cycle and colony formation assay were observed. Western blot was used to verify the effect of QTEZ on the pathway proteins including phosphoinositide 3-kinase(PI3K), phosphorylated PI3K(p-PI3K), protein kinase B(AKT), and phosphorylated AKT(p-AKT). RT-qPCR and Western blot were used to detect the effects of QTEZ on cell cycle-related targets such as CDK inhibitor 1(P21), cyclin D1(CCND1), and cyclin-dependent kinase 4(CDK4). The results showed that a total of 158 components were identified by QTEZ, and 375 component and disease intersecting targets were obtained, 21 core components and 40 core targets were obtained after constructing the network, and GO and KEGG enrichment showed signaling pathways such as PI3K/AKT. QTEZ and its decomposed formulae could promote the 5-fluorouracil-blocked cell cycle to resume operation, and all of them had different degrees of restoration effects on the set of colonies, among which QTEZ had the best restoration effect, and the Astragali Radix-Angelicae Sinensis Radix group had a focused effect on colony forming unit-erythrocyte. Western blot results indicated that there was no significant difference in the expression levels of pathway proteins among the groups. RT-qPCR and Western blot results showed that QTEZ could down-regulate P21 and up-regulate the protein and mRNA expression of CDK4 and CCND1. In conclusion, QTEZ and its decomposed formulas can exert a protective effect on hematopoietic stem cells with 5-fluorouracil-induced myelosuppression by promoting the normal operation of the cell cycle and colony formation, and the mechanism may be related to the down-regulation of the cell cycle-related targets of P21 and the up-regulation of CDK4 and CCND1. In addition, Astragali Radix-Angelicae Sinensis Radix can have a targeted protective effect on erythrocytes.
Animals ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Mice ; Fluorouracil/adverse effects* ; Male ; Antineoplastic Agents/adverse effects* ; Hematopoietic Stem Cells/cytology* ; Humans ; Signal Transduction/drug effects*

OBJECTIVE: To observe the clinical efficacy of 3D printing spinal external fixator combined with McKenzie therapy for patients with lumbar dics herniation (LDH). METHODS: Sixty patients with LDH between January 2022 and January 2023 were enrolled. Among them, 30 patients were given McKinsey training. According to different treatment methods, all patients were divided into McKenzie group and McKenzie + 3D printing group, 30 patients in each group. The McKenzie group provided McKenzie therapy. The McKenzie + 3D printing group were treated with 3D printing spinal external fixation brace on the basis of McKenzie therapy. Patients in both groups were between 25 and 60 years of age and had their first illness. In the McKenzie group, there were 19 males and 11 females, with an average age of (48.57±5.86) years old, and the disease duration was (7.03 ±2.39) months. The McKenzie + 3D printing group, there were 21 males and 9 females, with an average age of (48.80±5.92) years old, and the disease duration was(7.30±2.56) months. Pain was evaluated using the visual analogue scale (VAS), and lumbar spine function was assessed using the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) score. VAS, ODI and JOA scores were compared between two groups before treatment and at 1, 3, 6, 9 and 12 months after treatment. RESULTS: All patients were followed up for 12 months. The VAS for the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(6.533±0.860), (5.133±1.008), (3.933±0.868), (2.900±0.759), (2.067±0.640), (1.433±0.504), respectively. In the McKenzie group, the corresponding scores were (6.467±0.860), (5.067±1.048), (4.600±0.968), (3.533±1.008), (2.567±0.728), (1.967±0.809), respectively. The ODI of the McKenzie group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were (41.033±6.810)%, (37.933±6.209)%, (35.467±6.962)%, (27.567±10.081)%, (20.800±7.531)%, (13.533±5.158)%, respectively. For the McKenzie combined with 3D printing group, the corresponding ODI were(38.033±5.605)%, (33.000±6.192)%, (28.767±7.045)%, (22.200±5.517)%, (17.700±4.836)%, (11.900±2.771)%, respectively. The JOA scores of the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(8.900±2.074), (13.133±2.330), (15.700±3.583), (20.400±3.480), (22.267±3.084), (24.833±2.640), respectively. In the McKenzie group, the corresponding scores were(9.200±2.091), (12.267±2.406), (15.333±3.198), (18.467±2.240), (20.133±2.751), (22.467±2.849), respectively. Before the initiation of treatment, no statistically significant differences were observed in the VAS, ODI, and JOA scores between two groups (P>0.05). At 3, 6, 9, and 12 months post-treatment, the VAS in the McKenzie combined with 3D printing group was significantly lower than that in the McKenzie group, and the difference was statistically significant (P<0.05). The comparison of ODI between two groups at 1, 3, 6, 9, and 12 months post-treatment revealed statistically significant differences (P<0.05). At 6, 9, and 12 months post-treatment, the JOA score in the McKenzie combined with 3D printing group was significantly higher than that in the McKenzie-only group, and the difference was statistically significant (P<0.05). CONCLUSION The combination of 3D printed functional spinal external fixation brace with McKenzie therapy can significantly improve and maintain lumbar function in patients with LDH.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Intervertebral Disc Displacement/surgery* ; External Fixators ; Lumbar Vertebrae/surgery* ; Adult ; Braces ; Treatment Outcome

ObjectiveTo investigate the possible mechanism of Buzhong Yulin Decoction （补中愈淋汤） in the prevention and treatment of recurrent urinary tract infection. MethodsThe mouse models of recurrent urinary tract infection were established by uropathogenic Escherichia coli （UPEC） strain UTI89 by bladder perfusion， and the successful mouse models were randomly divided into a model group， an antibiotic group， and a low- and high-dose Buzhong Yulin Decoction group， with six mice in each group. In addition， 5 C57BL/6 mice without modelling were taken as blank group. The low- and high-dose Buzhong Yulin Decoction groups received 0.1 ml/10 g of decoction by gavage， with concentrations of 1.3 g/ml and 5.2 g/ml， respectively； the antibiotic group received 0.1 ml/10 g of levofloxacin hydrochloride solution with 5 mg/ml by gavage； the blank and model groups received 0.1 ml/10 g of distilled water by gavage. Each group was gavaged once a day for 7 consecutive days. The total number of urine marks， the number of central urine marks， and the total urine volume of the urine marks were observed by the urine marking test； HE staining was used to observe the histopathological changes in the bladder of mice； serum levels of the inflammatory factors interleukin 1β （IL-1β）， interleukin 6 （IL-6） and tumour necrosis factor α （TNF-α） were detected by ELISA； the morphology of the epithelial cells of bladder was observed by scanning electron microscopy； immunofluorescence assay to detect bladder tissue anti-UroPlakin 3A protein level and UPEC bacterial load； the spread plate method to detect urinary bacterial load and bacterial load of bladder epithelial cells； RT-PCR method to detect Ras-related protein Rab-11A （RAB11A） and Ras-related protein Rab-27B （RAB27B） mRNA level in bladder tissue； immunoblotting to detect microtubule-associated protein 1 light chain3 （LC3） and P62 protein levels in bladder tissue. ResultsCompared with the blank group， the bladder epithelial cell layers were lost and showed abnormal morphology in mice of the model group； bladder tissue UroPlakin 3A protein and RAB11A and RAB27B mRNA levels reduced， the total number of urine marks， the number of central urine marks， bladder tissue UPEC bacterial load， urinary bacterial load， bacterial load in bladder epithelial cells， serum IL-1β， IL-6， and TNF-α levels， and LC3 and P62 protein levels in bladder tissue all elevated （P＜0.05 or P＜0.01）. Compared with the model group， the bladder epithelial cell layers were intact and the morphology of epithelial cells were regular in the low- and high-dose Buzhong Yulin Decoction groups； the average surface area of bladder epithelial cells reduced， the levels of UroPlakin 3A protein and RAB11A and RAB27B mRNA in bladder tissues elevated， and total number of urine marks， the number of central urine marks， bladder tissue UPEC bacterial load， urinary bacterial load， bacterial load in bladder epithelial cells， serum IL-1β， IL-6， and TNF-α levels， and P62 protein levels in bladder tissue all reduced （P＜0.05 or P＜0.01）， but LC3 protein levels showed no statistically significant （P＞0.05）. In the antibiotic group， the bladder epithelial cells were partially missing and the morphology of epithelial cells was abnormal. Compared with the antibiotic group， the average surface area of the bladder epithelial cells in the mice increased in the low- and high-dose Buzhong Yulin Decoction groups， the bacterial load of the bladder epithelial cells decreased， and the P62 protein level of the bladder tissue decreased （P＜0.05）. When comparing between the low- and high-dose Buzhong Yulin Decoction groups， the differences in each index were not statistically significant （P＞0.05）. ConclusionBuzhong Yulin Decoction may prevent and treat recurrent urinary tract infection by repairing the bladder mucosal barrier， increasing RAB11A and RAB27B level and enhancing autophagy in bladder tissues， thereby facilitating bacterial clearance from bladder epithelial cells and reducing the bacterial load of bladder epithelial cells.

ObjectiveSpatial working memory (SWM) is an important function in cognitive behavior, and working memory impairment can seriously affect the patient’s life and cause great stress to the patient. Intermittent theta burst stimulation (iTBS) has been shown to regulate working memory function by entrainment of neural oscillations in different frequencies of the brain, but its regulation of working memory-related neural oscillations and their synchronization is not clear. The purpose of this study was to study the effect of iTBS on neural oscillation and synchronization in local and transbrain regions of rats, and to explore the mechanism of iTBS in regulating working memory. MethodsTwenty-four rats were randomly divided into four groups according to their age and whether they received iTBS stimulation (AS: adult stimulation group, AC: adult control group, ES: elderly stimulation group, EC: elderly control group). Using the methods of time-frequency distribution, phase synchronization and phase-amplitude coupling analysis, the changes of local field potential signal neural oscillations in the prefrontal and hippocampal brain regions of theta and gamma bands in the process of spatial working memory behavioral tasks in each group of rats were compared and analyzed, and the relationship between the changes of neural oscillations in the two brain regions and the changes in spatial working memory ability of rats was judged based on the Pearson correlation coefficient. ResultsWith the increase of age, the time taken by the elderly rats to learn the spatial working memory task rules increased significantly (P=0.005 6), and the time taken by iTBS stimulation to learn the SWM task rules in adult rats (P=0.001 1) and elderly rats(P=0.009 0) was shortened. At the same time, compared with adult rats, the time-frequency energy of theta and gamma band neural oscillations in the prefrontal and hippocampal brain regions of elderly rats (theta: P<0.000 1; gamma: P<0.000 1) and phase-amplitude coupling across brain regions (PFC-HPC: P=0.000 2; HPC-PFC:P=0.027 7) decreased to a certain extent, and iTBS stimulation could increase the time-frequency energy of neural oscillations of adult rats (theta: P<0.000 1; gamma: P<0.000 1) and elderly rats (theta: P=0.014 4; gamma:P=0.000 6) and the phase-amplitude coupling effect across brain regions in elderly rats (PFC-HPC: P=0.018 0; HPC-PFC: P=0.022 1). In addition, the time-frequency energy and phase-amplitude coupling of signals in each frequency band of the two brain regions were positively correlated with the behavioral accuracy of rats, while the phase synchronization of theta band and gamma band neural oscillations in the two brain regions during working memory was not correlated with the behavioral accuracy. ConclusioniTBS can enhance SWM ability and cognitive function in elderly rats, and this improvement is associated with increased coupling of time-frequency energy and cross-brain phase amplitude of neural oscillations across theta and gamma bands during SWM tasks. Similarly, in adult rats, iTBS enhances SWM ability and cognitive function by increasing the time-frequency energy of theta and gamma band neural oscillations in both brain regions during SWM tasks. Furthermore, in addition to the main findings, this study provides evidence supporting the state-dependent effects of iTBS stimulation to some extent.

convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective To discuss the application effect of using a stone extractor balloon catheter to assist in crossing the anastomotic stenosis in treatment of anastomotic biliary stenosis after liver transplantation using endoscopic retrograde cholangiopancreatography(ERCP).Methods Clinical data of 48 patients who developed anastomotic biliary stenosis after liver transplantation and underwent ERCP treatment were collected.Upon unsuccessful use of a dilation catheter to cross the stricture,attempts were made to cross the anastomotic biliary stenosis by using a stone extractor balloon catheter.The success rate of the procedure was recorded,intraoperative conditions were observed,treatment outcomes and complications were analyzed.Results The main presenting symptoms in the 48 patients on admission were abdominal discomfort(32 patients),fever(7 patients),pruritus(4 patients),jaundice(3 patients),and no obvious symptoms(2 patients).Preoperative magnetic resonance cholangiopancreatography(MRCP)examination revealed isolated stricture of the anastomotic site in 35 cases,and stricture associated with stones in 13 cases.Using the stone extractor balloon catheter as a guide,guidewire crossing of the anastomotic stenosis was successful in 26 cases,resulting in a success rate of 54.17%(26/48).Through statistical analysis of the successful group and the failed group,there was a significant difference in whether the distal biliary dilatation between the two groups,and the difference was statistically significant(χ2 = 8.39,P = 0.004).In the 26 successfully treated cases,alanine transaminase(ALT),aspartate transaminase(AST),γ-glutamyl transpeptidase(γ-GT),alkaline phosphatase(ALP),and total bilirubin(TBiL)levels decreased significantly 48 hours after the procedure(P<0.05),and no serious complications occurred.Conclusion The use of a stone extractor balloon catheter significantly increases the success rate of crossing anastomotic stenosis in the treatment of anastomotic biliary stenosis after liver transplantation,especially in cases with distal dilatation of the common bile duct.This approach is safe and worth promoting.

Objective An isotemporal substitution model was used to explore the associations between activities including 10 minutes per day of physical activity(PA),sedentary behavior(SB),and sleep(SLP),and depressive symptoms among vocational school students with and without depressive symptoms.Methods Questionnaire survey was conducted on grade one to grade three students attending vocational schools in Shanghai and Jiangsu Province from Dec 2021 to Jan 2022.Fourteen schools were selected using the convenience cluster sampling method.The selected students were categorized into depressive symptoms group and non-depressive symptoms group according to the Centre for Epidemiologic Studies Depression Scale(CES-D)scores.Results A total of 40 339 questionnaires were collected,of which 10 086 were able to clearly remember the time of physical activity in the past week,and 8 149 were valid after data cleaning.According to the valid questionnaires,5 496 students(67.44%)were in the non-depressive symptoms group and 2 653(32.56%)were in the depressive symptoms group.The mean age of the students were(16.70±1.19)years.In the non-depressive symptoms group,substituting moderate physical activity(MPA)for all the other behaviors was negatively associated with CES-D scores,while substituting vigorous physical activity(VPA)for MPA and SB was positively associated with CES-D scores.In the depressive symptoms group,substituting walking,SB,and SLP with MPA was negatively associated with CES-D scores,respectively.The associations of MPA substituted for walking,SB,and SLP with CES-D scores were much stronger in the depressive symptoms group than in the non-depressive symptoms group.Conclusion The detection rate of depressive symptoms was high among vocational students.Substituting MPA for walking,SB,and SLP were negatively associated with CES-D scores,with a stronger association observed in the depressive symptoms group than in the non-depressive symptoms group.