BackgroundThe global prevalence of depressive disorders is high， with a significant treatment gap remaining. Escitalopram oxalate， as a commonly used antidepressant in clinical practice， has a single target and is prone to cause adverse reactions such as gastrointestinal discomfort. The traditional Mongolian medicine Zadi-5 pills has a multi-target anti-depression mechanism and unique advantages such as improving the intestinal flora. However， there is currently a lack of randomized controlled trial evidence for the combined treatment of first-episode depression， along with insufficient research on its metabolic safety and potential drug interactions. ObjectiveTo explore the efficacy and safety of Zadi-5 pills combined with escitalopram oxalate in the treatment of the first-episode depression， so as to provide references for Mongolian medicine in depression management. MethodsA randomized controlled trial was conducted. A total of 103 patients with first-episode depression who were treated in the outpatient or inpatient departments of the Inner Mongolia Autonomous Region Mental Health Center from January 2023 to December 2024 and met the diagnostic criteria for depressive episode as defined in International Classification of Diseases， tenth edition （ICD-10） were included. Random numbers were generated using the RAND function in Excel software， and the patients were divided into the study group （n=52） and the control group （n=51）. Both groups received escitalopram oxalate treatment， starting from 5 mg/d and gradually increasing to 20 mg/d. The study group additionally received Zadi-5 pills， 13 pills per day. The treatment duration for both groups was 6 weeks. Before treatment and at the 2^nd， 4^th， and 6^th weeks of treatment， the severity of depressive symptoms was evaluated using the Hamilton Depression Scale-24 item （HAMD-24）. At these time points， blood was collected on an empty stomach at 7∶00 for the detection of liver function （aspartate aminotransferase， alanine aminotransferase）， triglycerides， and the blood concentration of escitalopram oxalate. ResultsA total of 100 patients completed the study， with 50 cases in the study group and the control group. The results of the repeated measures ANOVA showed that the interaction effect between group and time in the HAMD-24 score was statistically significant （F _interaction= 18.070， P<0.01）. At the end of the 4^th and 6^th weeks of treatment， the HAMD-24 score of the study group was lower than those of the control group （P<0.05）. At each time point after treatment， the reduction rate of the HAMD-24 score in the study group was higher than those of the control group， and the differences were all statistically significant （P<0.05）. The interaction effect between the triglyceride level groups and time was statistically significant （F_interaction=3.381， P<0.05）.After treatment， the triglyceride levels in the study group showed a downward trend， while those in the control group showed an upward trend. There was no statistically significant interaction effect between the groups and time for liver function （aspartate aminotransferase and alanine aminotransferase） and the blood concentration of escitalopram oxalate （P>0.05）. ConclusionCompared with escitalopram oxalate treatment alone， the combination of Zadi-5 pills and escitalopram oxalate is more effective in treating the first-episode depression， without increasing the risk of liver damage. The combined medication may have a potential beneficial effect on lipid metabolism. ［Funded by Inner Mongolia Autonomous Region Health Science and Technology Planning Project （number， 202202107）］

Objective: To explore the clinical and imaging characteristics of patients with regional odontodysplasia accompanied by hypodontia and to provide a reference for clinical diagnosis and treatment. Methods: This report presents the imaging manifestations, diagnosis, and treatment of a case of regional odontodysplasia (RO) accompanied by hypodontia. It includes a retrospective summary of the dynamic changes in the imaging characteristics of the affected teeth over a 5-year period, along with a comparative analysis of the literature. The patient was a 9-year-old female who presented to the Clinic of Oral Rare and Genetic Diseases of our hospital with the chief complaint of “discomfort for over seven months following the extraction of the teeth in the left mandibular region.” Based on her clinical manifestations and imaging findings, she was diagnosed with RO in the left mandible and with hypodontia of permanent teeth 12 and 34. A treatment plan was formulated, and long-term follow-up was conducted. The current radiographic images were compared with previous imaging data to summarize the developmental changes in her teeth, and a comparative analysis was also performed with the literature to identify similarities and differences with previously reported RO dental characteristics. Results: During the follow-up period, the patient's symptoms did not worsen, and a conservative observation approach was adopted; the treatment plan was decided after the eruption of the affected teeth. By comparing and analyzing imaging data from three ages (4.5, 8.5, and 9 years old), it was determined that the deciduous and permanent teeth in the left mandible of this patient exhibited typical “ghost” radiographic features, alongside hypodontia of teeth 12 and 34, as well as the delayed development of tooth 35. A literature review and analysis indicated that RO manifests clinical characteristics such as delayed tooth eruption, reduced tooth size, and yellow crowns, along with typical “ghost” radiographic appearances. Treatment requires a personalized approach based on the patient’s specific condition. To date, only five cases of RO patients with hypodontia have been reported, while the delayed development of permanent tooth buds has not yet been documented. Conclusion For patients with RO, dynamic imaging evaluation plays a critical role in early diagnosis. RO is associated with hypodontia and delayed tooth germ development. Long-term follow-up and personalized treatment plans are the key to RO treatment.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.

Objective To evaluate the effect of sodium hypochlorite and Ultra Clean on root canal cleaning and dentin structure.Methods A total of 129 single canal isolated teeth were collected and root canal was prepared to M # with Waveone Gold nickel titani-um file.After preparation,they were divided into 3 groups by random number table according to irrigant:group A sodium hypochlorite+normal saline,group B sodium hypochlorite+EDTA,and group C sodium hypochlorite+Ultra Clean.The dye was stained with 1％methylene blue solution,and the penetration depth and range of the dye solution were observed under a type microscope.The removal of debris and stain layer in the root canal was observed by digital camera and scanning electron microscope.The change of dentin micro-structure was analyzed by Fourier infrared spectrometer.Results In the upper middle part of the root canal,the penetration depth and range of group C were greater than those of groups A and B(P＜0.05);the percentage of debris in group C was lower than that of groups A and B(P＜0.05),and the stain layer score in groups B and C was lower than that of group A(P＜0.05).In the lower root ca-nal segment,groups B and C were superior to group A in the evaluation of permeability,debris and stain removal(P＜0.05).The demineralization ability and exposure of dentin collagen fiber in group C were higher than those in group A and blank group(P＜0.05).Conclusion Sodium hypochlorite combined with Ultra Clean is considered to have good cleaning effect and strong demineralization ability,but it may slightly increase the exposure of organic matter such as collagen fiber.

Objective:To explore the clinical efficacy of periosteal induction technique combined with transfer of sural neurovascular flap in treatment of post-traumatic osteomyelitis of calcaneus with soft tissue defect.Methods:Clinical data, from January 2017 to December 2022, of 17 patients in the Army Institute for Traumatic Orthopaedics, the 920th Hospital of Joint Service Force of the Chinese People’s Liberation Amy with post-traumatic calcaneal osteomyelitis combined with soft tissue defect were retrospectively studied. The patients were 11 males and 6 females, with 46.5 (17-68) years in average. All patients received surgical treatment with periosteal induction technique in 2 phased surgies. Thorough debridement, antibiotics blended bone cement filling and wound coverage with sural neurovascular flap were carried out in phase-I surgery; The phase-II surgery were performed at 6-8 weeks after infection control to remove bone cement and then to transfer bone grafts for periosteal induction. After surgery, flap healing and infection control were observed. The infection control, pain improvement, recovery of ankle function and improvement of quality of life were evaluated by comparison of following parameters before and after surgery per phase: infection indicators [white blood cell count (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)], Visual Analogue Scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and MOS 36-item Short form Health Survey (SF-36, Boston Institute of Health, USA).Results:All 17 patients completed the two-phased surgical treatment, with an average interval of 9.4 (8-16) weeks between phase-I and phase-II surgery. All patients were included in the postoperative follow-up of 25.8 (13-40) months. After debridement in phase-I surgery, the sizes of soft tissue defect were found at 3.0 cm×2.0 cm-6.0 cm×8.0 cm. All flaps survived from the reconstructive surgery of sural neurovascular flap. Postoperative distal flap necroses occurred to 4 patients but all healed after further debridement. Recurrence of postoperative infection occurred to 2 patients and the infection control was achieved after the phase-I rescue surgery. Good outcomes without recurrence of infection were achieved after phase-II surgery. The postoperative follow-up at 1 year after phase-II surgery showed a statistically significant improvement of infection in blood indicators and reductions in VAS score, AOFAS ankle-hindfoot score and SF-36 score in comparison with those before surgery ( P<0.05). In addition to WBC, there were also significant differences in pairwise comparisons between each group at different time points ( P<0.05). Conclusion:In the treatment of post-traumatic calcaneal osteomyelitis with soft tissue defect, a combination of periosteal induction technique and sural neurovascular flap is beneficial to infection control, bone defect reconstruction, recovery of ankle function and improvement of quality of life.

Background:Rhei Radix et Rhizoma has been traditionally used as a potent laxative for centuries due to its remarkable efficacy.Raw pieces of Rhei Radix et Rhizoma(RP)are known for their strong laxative effects,often accompanied by side effects,while steamed Rhei Radix et Rhizoma pieces(SP)possess a milder laxative effect and are widely used clinically.However,there is a lack of comprehensive evidence examining the mechanisms underlying SP's effectiveness,particularly from a bioavailability perspective.Objective:This study aimed to investigate the impact of the steaming process on the in vivo disposition of RP and SP through pharmacokinetics,tissue distribution,and excretion assays.Methods:An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantitative analysis of prototype anthraquinones and their glucuronide metabolites.Pharmacokinetic,tissue distribution,and excre-tion assays were conducted in constipation rats following oral administration of RP and SP.Blood,tissue,urine,and fecal samples were collected and analyzed to compare the absorption,distribution,metabolism,and excretion profiles of anthraquinones,high-lighting differences in bioavailability and safety between RP and SP.Results:Compared with the RP group,the SP group showed significantly reduced area under the plasma concentration-time curve,mean residence time,and half-life time values for rhein-8-O-β-D-glucopyranoside,rhein,emodin,aloe-emodin,and their glucuronide metabolites.The clearance values were significantly increased in the SP group.These results demonstrate that SP led to lower exposure levels and higher elimination rates of these components compared with RP.Additionally,these compo-nents were primarily distributed in the large intestine,where they exerted their laxative effects.Glucuronide metabolites were mainly excreted through urination,while prototype components were excreted in both urine and feces.Notably,the cumulative excretion of aloe-emodin,emodin,rhein,and their glucuronide metabolites was significantly higher in both urine and feces after SP administra-tion,indicating that SP enhances the excretion of these components compared with RP.Conclusion:The findings suggest that SP reduced anthraquinone exposure levels while enhancing their excretion,demonstrating that the steaming process significantly promotes the elimination of key components.This study provides a comprehensive analysis of how steaming alters the in vivo disposition of Rhei Radix et Rhizoma,offering a scientific basis for the improved safety and clinical use of SP.These insights not only clarify the mechanistic differences between RP and SP but also contribute to a broader understanding of processing-induced modifications in Chinese medicines.This research paves the way for optimizing Chinese medicine processing techniques to enhance the safety and efficacy of herbal therapies.

Objective:To explore the application value of Holo-Hilbert spectral analysis (HHSA) in the analysis of tremor in Parkinson′s disease (PD) and essential tremor (ET).Methods:A total of 59 patients with PD with motor symptoms and 46 patients with ET were selected from the patients visiting the Department of Neurology, Qilu Hospital of Shandong University (Qingdao) between January 2022 and April 2024, and the original tremor information and myoelectric activity were recorded by accelerometer and electromyography under the condition of no weight bearing and 1 000 g weight bearing. Fourier transform (FT) and HHSA were used to convert the original data, and the effectiveness of HHSA for tremor analysis was verified by comparing the tremor characteristics under the two conversion methods.Results:The tremor data of 59 PD patients and 46 ET patients were converted by HHSA, and the amplitude modulation frequency-carrier frequency spectrum was obtained; and compared with FT, the noise-related spectrum and insignificant peaks were eliminated, and the uniqueness of tremor was maintained. And the tremor peak frequencies of PD patients under the two methods were similar, both being 4-6 Hz; the tremor peak frequencies of ET patients under the two methods were also similar, both being 6-12 Hz. The tremor peak frequencies of FT and HHSA transform in the upper limb resting state of PD patients were (4.93±0.73) Hz and (4.83±0.93) Hz, respectively, with no statistically significant difference between the two groups ( t=0.371, P=0.695). The tremor peak frequencies of FT and HHSA transform in the left upper limbs of ET patients were (8.59±2.23) Hz and (8.57±2.29) Hz, respectively ( t=0.273, P=0.968), in the right upper limbs were (8.09±1.87) Hz and (8.20±2.11) Hz, respectively ( t=0.141, P=0.890), both with no statistically significant differences. There were no significant differences in the tremor peak frequencies of the two methods in the same limb and the same state. PD patients and ET patients who showed harmonics under FT did not show harmonics after HHSA transform. Conclusions:The effectiveness and accuracy of HHSA and FT in the analysis of tremor in PD and ET patients are similar. HHSA is an effective tool for analyzing tremor and the problem of harmonics can be solved by HHSA, and the amplitude modulation frequency-carrier frequency spectrum can be used to analyze the relationship between accelerometer and electromyographic data, providing a possible way to study the mechanism of tremor.

Treatment of large segmental defects of long bone has always been a major challenge for the medical community. At present, the bone defects have been treated by autologous or allogeneic bone grafting, free vascularized fibula grafting, Masquelet technique, Ilizarov technique, cylindrical mesh technique and other methods. However, these technical steps are relatively complicated and their cycles are long so that it is difficult to repair the bone defects immediately after surgery and carry out early weight bearing and functional exercise. In recent years, customized 3D printed microporous titanium (tantalum) prostheses have provided a safe and feasible treatment method for repair of these large bone defects. 3D printed microporous titanium (tantalum) prosthesis can accurately reconstruct the anatomical shape of a bone defect, and simultaneously provide stable biomechanical support for the overall bone structure by its mechanical strength of titanium alloy, demonstrating obvious advantages in the repair and regeneration of bone defects. This paper reviewed the characteristics, design requirements, mechanical properties, vascularization challenges and clinical applications of 3D printed microporous titanium (tantalum) prosthesis, and looked ahead to the future development of this new 3D printed prosthesis.

Objective:To evaluate the clinical efficacy of the intelligent robot-assisted fracture reduction system (RAFR) in the treatment of unstable pelvic fractures.Methods:A retrospective study was conducted to analyze the clinical data of the 19 patients with unstable pelvic fracture who had been admitted to Department of Orthopaedics, The 920th Hospital of the Joint Logistics Support Force of the PLA from March to September 2024. There were 11 males and 8 females, with an age of (42.8±13.1) years. The Tile classification: 3 cases of type B1, 5 ones of type B2, 3 ones of type B3, 5 ones of type C1, and 3 ones of type C2. The time from injury to surgery was (9.3±3.5) days. All patients underwent surgery assisted by RAFR. According to the severity of injury, the pelvic posterior ring was fixed in all the 19 patients by sacroiliac joint screws. The anterior pelvic ring was fixed by pubic branch screws in 12 patients, and fixed by pubic branch screws combined with external fixation brackets or simply with external fixation brackets in 7 patients. Variables recorded were surgical time, intraoperative fluoroscopy frequency, intraoperative bleeding volume, fracture reduction quality, pelvic function at the last follow-up, and complications.Results:All the 19 patients achieved successful reduction with the help of RAFR. In this cohort, surgical time averaged (207.2±31.2) minutes, intraoperative bleeding volume 100 (80, 130) mL, fluoroscopy frequency (36.6±12.4) times, and residual pelvic displacement (6.1±3.3) mm. Postoperative reduction quality assessed by the Matta scoring was excellent in 7 cases, good in 9 ones, and fair in 3 ones. The follow-up duration for this cohort was (10.0±2.7) months. By the Majeed system, the pelvic function at the last follow-up scored (85.7±6.3) points, giving 9 excellent and 10 good cases. No such complications as incisional infection, fracture redisplacement, neurovascular injury, or implant loosening/breakage occurred during follow-up.Conclusion:In the treatment of unstable pelvic fractures, the RAFR can lead to good reduction quality and satisfactory clinical outcomes due to its advantages of precision, safety and simple handling.