ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop （TTFL） of biorhythm in the rat model of non-alcoholic fatty liver disease （NAFLD） and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank （n=20）， model （n=15）， and low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） modified Ditan tang （n=10） groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage， and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid （NEFA） assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining， and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 （BMAL1/ARNTL） in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1， circadian locomotor output cycles kaput （CLOCK）， period circadian clock 2 （PER2）， and cryptochrome1 （Cry1） in the hypothalamus and liver were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed elevated levels of TG， TC， LDL-C， AST， and ALT （P<0.01） and a lowered level of HDL-C （P<0.05） in the serum， elevated levels of TG and NEFA in the liver （P<0.01）， pyknosis and deep staining of hypothalamic neuron cells， and a large number of vacuoles in the brain area. In addition， the model group showed lipid deposition in the liver， up-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.01）， and down-regulated mRNA and protein levels of Cry1 and PER2 （P<0.01） in the hypothalamus and liver. Compared with the model group， all the three modified Ditan tang groups showed lowered levels of TG， TC， LDL-C， ALT， and AST （P<0.05， P<0.01） and an elevated level of HDL-C （P<0.05） in the serum， and lowered levels of TG and NEFA （P<0.05， P<0.01） in the liver. Furthermore， the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells， reduced lipid deposition in the liver， down-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.05， P<0.01）， and up-regulated mRNA and protein levels of Cry1 and PER2 （P<0.05， P<0.01） in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK， BMAL1， Cry1， and PER2 in the TTFL of NAFLD rats.

BackgroundAlcohol dependence patients are prone to relapse after their attempts to quit drinking， which poses a considerable threat to their physical and mental health and creates a heavy burden on their families. Currently， empowerment education is increasingly being utilized in the rehabilitation management of chronic diseases， but there remains a striking lack of empirical research on the application of "Internet +" empowerment education based on timing it right in alcohol dependence patients. ObjectiveTo explore the impact of "Internet +" empowerment education based on timing it right on patients with alcohol dependence， in order to maximize the reduction in relapse rates， craving for alcohol and severity of anxiety symptoms. MethodsA total of 120 patients who were hospitalized in the Department of Addiction Medicine， Hebei Provincial Mental Health Center from May 2022 to April 2023 and met the diagnostic criteria for alcohol dependence in the International Classification of Diseases， tenth edition （ICD-10） were enrolled， and they were classified into study group （n=62） and control group （n=58） using random number table methods. Both groups received standard medication and routine care. Additionally， study group underwent a 6-month "Internet +" empowerment education based on timing it right. At baseline， all subjects were assessed using Penn Alcohol Craving Scale （PACS） and Self-rating Anxiety Scale （SAS）. Three months and six months after intervention， assessments were conducted using PACS， SAS and Michigan Alcoholism Screening Test （MAST）. ResultsThe relapse rates after three and six months of intervention were both lower in study group than those in control group， with statistically significant differences （χ²=8.575， 8.828， P<0.01）. ANOVA with repeated measures on PACS total score and scores of each item revealed a significant time effect， group effect and time×group interaction effect （F=159.714~837.751， 84.645~393.606， 24.302~137.896， P<0.01）. And significant time effect， group effect and time×group interaction effect were also reported on SAS scores （F=166.237， 65.325， 24.724， P<0.01）. Conclusion"Internet +" empowerment education based on timing it right may help reduce relapse rates， alcohol cravings and severity of anxiety symptoms among patients with alcohol dependence. ［Funded by 2023 Annual Hebei Provincial Medical Scientific Research Project Plan （number， 20231537）］

This study explores the effect of total secondary ginsenosides(TSG) on apoptosis and energy metabolism in H9c2 cells under hypoxia and its potential mechanisms. H9c2 cell viability was observed and the apoptosis rate was calculated to determine suitable intervention concentrations of TSG, antimycin A complex(AMA), and coenzyme Q10(CoQ10), along with the duration of hypoxia. H9c2 cells at the logarithmic phase were divided into a normal group, a model group, a TSG group, an AMA group, a TSG+AMA group, and a CoQ10 group. All groups, except the normal group, were treated with their respective intervention drugs and cultured under hypoxic conditions. Adenosine triphosphate(ATP) content and creatine kinase(CK) activity were measured using an ATP chemiluminescence assay kit and a CK colorimetric assay kit. Flow cytometry was used to assess apoptosis rates, and Western blot evaluated the expression levels of apoptosis-related proteins, including B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cysteinyl aspartate-specific protease(caspase)-3, caspase-8, and caspase-9, as well as mitochondrial biogenesis-related proteins peroxisome proliferator-activated receptor-γ coactivator 1α(PGC-1α), estrogen-related receptor-α(ERRα), nuclear respiratory factor(NRF)-1, NRF-2, peroxisome proliferator activated receptor-α(PPARα), and Na~+-K~+-ATPase. RT-PCR was employed to analyze the mRNA expression of mitochondrial biogenesis factors, including PGC-1α, ERRα, NRF-1, NRF-2, PPARα, mitochondrial transcription factor A(TFAM), mitochondrial cytochrome C oxidase 1(COX1), and mitochondrial NADH dehydrogenase subunit 1(ND1), ND2. The selected intervention concentrations were 7.5 μg·mL~(-1) for TSG, 10 μmol·L~(-1) for AMA, and 1×10~(-4) mol·L~(-1) for CoQ10, with a hypoxia duration of 6 h. Compared with the normal group, the model group showed decreased ATP content and CK activity, increased apoptosis rates, decreased Bcl-2 expression, and increased Bax, caspase-3, caspase-8, and caspase-9 expression in H9c2 cells. Additionally, the protein and mRNA expression levels of mitochondrial biogenesis-related factors(PGC-1α, ERRα, NRF-1, NRF-2, PPARα), mRNA expression of TFAM, COX1, and ND1, ND2, and protein expression of Na~+-K~+-ATPase in mitochondrial DNA, were also reduced. In the TSG and CoQ10 groups, ATP content and CK activity increased, and apoptosis rates decreased compared with those in the model group. The TSG group showed decreased protein expression of apoptosis-related proteins Bax, caspase-3, caspase-8, and caspase-9, increased protein and mRNA expression of mitochondrial biogenesis factors PGC-1α, ERRα, NRF-1, and PPARα, and increased NRF-2 protein expression and TFAM mRNA expression in mitochondrial DNA. Conversely, in the AMA group, ATP content and CK activity decreased, the apoptosis rate increased, Bcl-2 expression decreased, and Bax, caspase-3, caspase-8, and caspase-9 expression increased, alongside reductions in PGC-1α, ERRα, NRF-1, NRF-2, PPARα protein and mRNA expression, as well as TFAM, COX1, ND1, ND2 mRNA expression and Na~+-K~+-ATPase protein expression. Compared with the TSG group, the TSG+AMA group exhibited decreased ATP content and CK activity, increased apoptosis rates, decreased Bcl-2 expression, and increased Bax, caspase-3, caspase-8, and caspase-9 expression, along with decreased PGC-1α, ERRα, NRF-1, NRF-2, and PPARα protein and mRNA expression and TFAM, COX1, and ND1, ND2 mRNA expression. Compared with the AMA group, the TSG+AMA group showed increased CK activity, decreased apoptosis rate, increased Bcl-2 expression, and decreased Bax, caspase-8, and caspase-9 expression. Additionally, the protein and mRNA expression of PGC-1α, ERRα, NRF-1, PPARα, mRNA expression of TFAM, COX1, ND1, ND2, and Na~+-K~+-ATPase protein expression increased. In conclusion, TSG enhance ATP content and CK activity and inhibit apoptosis in H9c2 cells under hypoxia, and the mechanisms may be related to the regulation of PGC-1α, ERRα, NRF-1, NRF-2, PPARα, and TFAM expression, thus promoting mitochondrial biogenesis.
Apoptosis/drug effects* ; Ginsenosides/pharmacology* ; Energy Metabolism/drug effects* ; Mitochondria/metabolism* ; Animals ; Rats ; Cell Line ; Cell Hypoxia/drug effects* ; Organelle Biogenesis ; Adenosine Triphosphate/metabolism* ; Humans ; Cell Survival/drug effects*

Objective: To assess the effectiveness of vertebral cement augmentation (VCA) at upper instrumented vertebra (UIV) and UIV+1 in preventing proximal junction complications in correction surgery for adult spinal deformity patients. Methods: A literature search was conducted on Web of Science, PubMed, and Cochrane Library databases for comparative studies published before December 30th, 2024. Two reviewers independently screened eligible articles based on the inclusion and exclusion criteria, assessed study quality with Newcastle-Ottawa scale, and extracted data like study characteristics, surgical details, primary and secondary outcomes. Data analysis was performed using Review Manager 5.4 and Stata software. Results: Of all 513 papers screened, a meta-analysis was conducted on 7 articles, which included 333 cases in the VCA group and 827 cases in the control group. Patients in the VCA group had significantly older age and lower T score than patients in the control group. Although there was no statistically significant difference in the incidence of proximal junctional failure between the 2 groups, the results of the meta-analysis showed that the incidence of proximal junctional failure and the need for revision surgery were reduced by 36% and 71%, respectively, in the VCA group. One study reported 2 clinically silent pulmonary cement embolism and 1 patient requiring surgical decompression for cement leak into the spinal canal. Conclusion This meta-analysis supported the use of VCA in corrective surgery for spinal deformities patients, especially in patients with advanced age and osteoporosis.

Objective: To assess the effectiveness of vertebral cement augmentation (VCA) at upper instrumented vertebra (UIV) and UIV+1 in preventing proximal junction complications in correction surgery for adult spinal deformity patients. Methods: A literature search was conducted on Web of Science, PubMed, and Cochrane Library databases for comparative studies published before December 30th, 2024. Two reviewers independently screened eligible articles based on the inclusion and exclusion criteria, assessed study quality with Newcastle-Ottawa scale, and extracted data like study characteristics, surgical details, primary and secondary outcomes. Data analysis was performed using Review Manager 5.4 and Stata software. Results: Of all 513 papers screened, a meta-analysis was conducted on 7 articles, which included 333 cases in the VCA group and 827 cases in the control group. Patients in the VCA group had significantly older age and lower T score than patients in the control group. Although there was no statistically significant difference in the incidence of proximal junctional failure between the 2 groups, the results of the meta-analysis showed that the incidence of proximal junctional failure and the need for revision surgery were reduced by 36% and 71%, respectively, in the VCA group. One study reported 2 clinically silent pulmonary cement embolism and 1 patient requiring surgical decompression for cement leak into the spinal canal. Conclusion This meta-analysis supported the use of VCA in corrective surgery for spinal deformities patients, especially in patients with advanced age and osteoporosis.

Objective:To investigate the surgical outcomes of congenital cervicothoracic scoliosis (CTS) patients with Klippel-Feil syndrome (KFS) and prognostic characteristics across different subtypes.Methods:A retrospective case series study is conducted. Clinical and radiographic data of 41 CTS patients with KFS who underwent hemivertebra resection with instrumentation at Department of Orthopedic Surgery, Nanjing Drum Tower Hospital from March 2012 to September 2022, with a minimum follow-up of two years, were analyzed. The cohort included 16 males and 25 females, aged (8.6±3.7) years (range: 3 to 15 years). Preoperative, immediate postoperative, and final follow-up cervicothoracic deformity parameters were compared. Patients were classified into three subtypes based on preoperative coronal alignment: shoulder-neck type (type A, 16 cases), trunk-tilt type (type B, 16 cases), and thoracic compensatory curve type (type C, 9 cases). The severity of KFS and the incidence of distal curve progression among subtypes were analyzed. Repeated measurement data were compared by repeated measurement ANOVA, pairwise comparison within groups was performed by Bonferroni method, and categorical variables were compared by Chi-square test or Fisher exact probability method.Results:All patients underwent successful surgery. Twenty-one patients (53.7%) had cervical fusion of ≥3 segments, and 63.1% (82/130) of fused cervical segments were located proximally to the instrumentation. Postoperative cervicothoracic Cobb angle, head tilt, head shift, neck tilt, and clavicle angle significantly improved (all P<0.05). The proportion of patients with cervical fusion of ≥3 segments was higher in types B and C (17/25) than that in type A (5/16) ( χ2=5.299, P=0.021). Four type B (4/16) and 5 type C (5/9) patients underwent long-segment fixation, with stable coronal alignment postoperatively. The remaining patients received short-segment fixation. In the short-segment group, the incidence of distal curve progression was significantly higher in types B and C (8/16) than that in type A (1/16) ( P=0.015). Ultimately, 3 type B patients underwent revision surgery, and 1 type C patient met the criteria for revision (distal compensatory thoracic or lumbar curve>40°). Conclusions:CTS patients with KFS are predisposed to develop significant coronal malalignment involving trunk tilt (type B) or thoracic compensatory curve (type C) before surgery. Following hemivertebra resection with short-segment fixation, such patients have a high risk of distal curve progression and potential need for revision surgery.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To explore a selective resection strategy for combined lumbosacral hemivertebra (LSHV) and thoracolumbar hemivertebra/lumbar hemivertebra (TLHV/LHV) double-balanced hemivertebra deformities.Methods:A retrospective analysis was conducted on 21 patients aged over 10 years with lumbosacral and thoracolumbar or lumbar combined hemimetameric segmental shift (HMMS) deformities who underwent surgery at Nanjing Drum Tower Hospital between May 2009 and October 2022. The cohort included 7 males and 14 females, with a mean surgical age of 21.5±10.9 years (range: 12-55 years) and a mean follow-up duration of 32.8±15.9 months (range: 24-74 months). Patients were divided into two groups based on preoperative coronal balance: the balanced group (Type A) and the unbalanced group (Type C). Radiographic parameters, including the major Cobb angle, lumbosacral take-off angle, kyphotic angle, coronal balance distance (CBD), and the deviation of the upper instrumented vertebra (UIV), were measured preoperatively, postoperatively, and at the final follow-up. Surgical complications were also recorded.Results:Of the 21 patients, 11 were classified as preoperatively balanced, and 10 as unbalanced. The deformity angular ratio of thoracolumbar to lumbosacral curves was significantly higher in the balanced group than in the unbalanced group (0.9±0.3 vs. 0.6±0.2; t=2.143, P=0.045). The preoperative main curve Cobb angles in the balanced and imbalanced groups were 71.3°±22.3° and 58.6°±8.2°, respectively. One week postoperatively, these angles were reduced to 38.4°±17.6° and 31.3°±5.6°, and were maintained at 40.0°±18.1° and 32.6°±5.6° at the final follow-up, all differences were statistically significant ( P<0.05). The preoperative lumbosacral take-off angles were 37.5°±9.1° in the balanced group and 36.7°±7.7° in the imbalanced group, which decreased to 18.4°±9.4° and 19.2°±5.5° at 1 week postoperatively, and remained at 19.4°±10.1° and 19.6°±5.8° at the final follow-up. These changes were also statistically significant ( P<0.05). In the balanced group, the UIV tilt angle, the CBD and the deviation of the UIV, were all significantly reduced compared to preoperative values ( P<0.05). Among the 21 patients, LSHV resection was performed in 15 cases, and TLHV/LHV resection was performed in 7 cases. Among the 15 patients with kyphosis, TLHV/LHV resection was performed in 6 cases. In the balanced group, 9 patients maintained type A postoperatively, including 4 patients with LSHV resection, 2 with TLHV/LHV resection, 2 with both LSHV and TLHV/LHV resection, 1 without resection of both hemivertebra. Two patients in the balanced group who underwent TLHV/LHV resection experienced postoperative deterioration to type C. In the unbalanced group, 8 cases with LSHV resection improved to type A, while 1 case with LSHV resection and 1 case with neither resection maintained C-type. In the LSHV resection group, CBD improved from 29.8±15.2 mm to 13.9±5.7 mm postoperatively and remained stable at 14.6±8.6 mm at final follow-up. Only 1 patient in this group experienced worsened coronal imbalance. In contrast, in the non-LSHV resection group, CBD worsened from 17.2 ± 8.7 mm to 19.7±12.1 mm postoperatively, progressing further to 20.5±13.0 mm at follow-up. Three patients in this group had worsening coronal imbalance, and 2 required revision surgery. Reported complications included 3 cases of internal fixation fracture, 1 case of proximal junctional kyphosis, and 1 case of acute incision infection. Conclusions:Effective resection of lumbosacral hemivertebrae is the preferred selective strategy, particularly for patients with preoperative coronal imbalance, as it significantly reduces the risk of worsening coronal imbalance and internal fixation-related complications. However, selective resection involving only TLHV or LHV without addressing LSHV in preoperatively balanced patients may increase the risk of postoperative coronal imbalance.

Objective:To investigate the effect of anterior and posterior selective fusion strategy on evolution of coronal pattern in patients with Lenke 5C adolescent idiopathic scoliosis (AIS) and whether upper end vertebra (UEV)-1 strategy in anterior surgery would have an effect on postoperative coronal balance.Methods:A total of 108 Lenke 5C AIS patients with at least 2 years follow-up who underwent anterior or posterior selective thoracolumbar fusion surgery from January 2005 to December 2020 were enrolled, with 51 patients in the anterior group and 57 patients in the posterior group. The patients were categorized into three groups (type A, C 7PL-CSVL<20 mm; type B, C 7PL-CSVL ≥20 mm with C 7PL toward the concave side of the main curve; and type C, C 7PL-CSVL≥20 mm with C 7PL toward the convex side of the main curve) to investigate the evolution of coronal balance of each preoperative coronal pattern at the anterior and posterior groups. Parameters such as thoracolumbar Cobb angle, rate of coronal imbalance, and SRS-22 score were recorded at preoperative, 1 week postoperatively, and final follow-up in both groups. Results:The differences of basic date between the two groups were not statistically significant except for the fusion level (5.2±0.7 vs. 5.6±0.9, t=2.497, P=0.014). In the anterior group, a total of 27 patients with preoperative type A, 23 patients with preoperative type A maintained type A at the 1 week postoperatively, and 2 of them were converted to type C at the final follow-up. Four patients with preoperative type A converted to type C at the 1 week postoperatively, and all of them returned to type A at the final follow-up. A total of 23 patients with preoperative type C, four patients with preoperative type C maintained type C at the 1 week postoperatively, and one of them maintained type C at the final follow-up. Nineteen patients with preoperative type C converted to type A at the 1 week postoperatively, and all of them maintained type A at the final follow-up. In the posterior group, a total of 26 patients with preoperative type A, 22 patients with preoperative type A maintained type A at the 1 week postoperatively, and only 2 of these patients converted to type C at the final follow-up. Four of the preoperative type A patients converted to type C at the 1 week postoperatively, and all of them returned to type A at the final follow-up. A total of 29 patients with preoperative type C, thirteen patients with preoperative type C maintained type C at the 1 week postoperatively, and 7 of them maintained type C at the last follow-up. Sixteen patients with preoperative type C converted to type A at the 1 week postoperatively, of whom two converted to type C at the final follow-up. For patients with preoperative type C the rate of coronal imbalance was significantly lower in the anterior group than in the posterior group both in the immediate postoperative period (17% vs. 45%, P<0.05) and at the final follow-up (4% vs. 31%, P=0.038). The rate of coronal imbalance at final follow-up was significantly lower in the UEV-1 group than in the UEV group in the posterior approach (3% vs. 38%, P<0.05), and there was no difference between the two groups in the anterior approach. There were no significant differences in radiographic parameters and SRS-22 scores between the two groups, except for the thoracic Cobb angle at the final follow-up, which was greater in the anterior group than in the posterior group at the final follow-up (19.5±7.3 vs.16.4±5.6, t=2.427, P=0.017). Multivariate logistic regression analysis revealed that anterior surgery and Risser were risk factors for postoperative CIB of preoperative type C ( OR=21.138, P=0.030 and OR=0.406, P=0.048 respectively). Conclusion:For patients with preoperative type A, both anterior and posterior procedures lead to a satisfactory reconstruction of coronal balance. In patients with preoperative type C, anterior surgery acquire a better reconstruction of coronal balance. The strategy of proximal UEV-1 was similar to the strategy of UEV in terms of restoring coronary balance in anterior approach and it was unable to lower the rate of postoperative coronal imbalance. In contrast, UEV-1 strategy in posterior surgery was effective in reducing the rate of postoperative coronal imbalance.