GBA1 gene mutation is an important genetic risk factor for Parkinson’s disease (PD). This paper reports a case of a 43-year-old male PD patient carrying a rare heterozygous Thr408Met mutation in the GBA1 gene identified through whole-exome sequencing, leading to a diagnosis of GBA1-associated PD. The patient’s motor symptoms were primarily characterized by bradykinesia and rigidity, without significant cognitive decline. Treatment with low-dose levodopa combined with a dopamine agonist resulted in significant symptomatic improvement.

BACKGROUND: The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD). METHODS: We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships. RESULTS: The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages. CONCLUSIONS: Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit. REGISTRATION No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?
Humans ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Dose-Response Relationship, Drug ; Randomized Controlled Trials as Topic

OBJECTIVE: To investigate the effect of autologous osteochondral tissue and periosteum transplantation on tendon-bone healing of rotator cuff in rabbits. METHODS: Twenty-four male New Zealand white rabbits were randomly divided into autologous osteochondral tissue and periosteum transplantation group (experimental group, n=12) and simple suture group (control group, n=12). Both groups were subjected to acute supraspinatus tendon injury and repaired with corresponding techniques. At 4, 8, and 12 weeks after operation, 4 specimens from each group were taken from the right shoulder joint for histological examination (HE staining, Masson staining, and Safranin O-fast green staining), and the left shoulder was subjected to biomechanical tests (maximum tensile load and stiffness). RESULTS: Both groups of animals survived until the completion of the experiment after operation. At 4 weeks after operation, both groups showed less collagen fibers and disorder at the tendon-bone junction. At 8 weeks, both groups showed reduced inflammation at the tendon-bone junction, with more organized and denser collagen fibers and chondrocytes. The experimental group showed better results than the control group. At 12 weeks, the experimental group showed typical tendon-bone transition structure, with increased generation of collagen fibers and chondrocytes, and the larger cartilage staining area. Both groups showed an increase in maximum tensile load and stiffness over time ( P<0.05). The stiffness at 4 weeks and the maximum tensile load at 4, 8, and 12 weeks in the experimental group were superior to control group, and the differences were significant ( P<0.05). There was no significant difference in stiffness at 8, 12 weeks between the two groups ( P>0.05). CONCLUSION Autologous osteochondral tissue and periosteum transplantation can effectively promote the fiber and cartilage regeneration at the tendon-bone junction of rotator cuff and improve the biomechanical effect of shoulder joint in rabbits.
Animals ; Rabbits ; Male ; Wound Healing ; Transplantation, Autologous ; Periosteum/transplantation* ; Rotator Cuff Injuries ; Rotator Cuff/surgery* ; Tendons/surgery* ; Biomechanical Phenomena ; Chondrocytes/transplantation* ; Tendon Injuries/surgery* ; Tensile Strength

Objective:To explore the mechanism of Jianpi Qingchang Decoction in the treatment of UC by integrating network pharmacology, bioinformatics, molecular docking and experimental verification.Methods:The effective components and targets of Jianpi Qingchang Decoction were obtained from TCMSP database, and UC data sets GSE16879, GSE48958 and GSE75214 were obtained from GEO database, and differentially expressed genes were screened; intersection targets were obtained through Venn diagram, and GO function and KEGG pathway enrichment analysis was performed. An intersection target PPI network was constructed using STRING database and topology analysis was performed; hub genes were screened through lasso regression and the expression consistency of core targets in the dataset was verified through logistic regression. A UC mouse model was established and hub genes were validated.Results:A total of 213 drug targets of Jianpi Qingchang Decoction were obtained, and 499 common intersection targets of GSE16879, GSE48958 and GSE75214 were obtained by differential gene expression analysis. Thirty intersection targets of Jianpi Qingchang Decoction and UC were obtained, mainly acting on IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, etc. PPI network topology analysis obtained 7 common intersection targets, including PTGS2, IL-1B, IL-6, MMP9, CXCL8, CCL2 and MMP2. IL-6 and MMP2 were selected as hub genes by lasso regression. Logistics regression analysis showed that IL-6 and MMP2 were risk factors for the disease. Compared with the model group, the expressions of IL-6 and MMP2 mRNA and protein in the colon tissue of the TCM group decreased ( P<0.05), and the morphology of colon tissue was improved compared with the model group. Conclusion:IL-6 and MMP2 are risk factors for UC, the therapeutic effect of Jianpi Qingchang Decoction is to mediate Il-17 signal pathway, TNF signal pathway and AGE-RAGE signal pathway in diabetic complications through the targets of IL-6, and MMP2, thereby treating UC.

Objective To develop a localized Salmonella serotyping method based on multiplex nanopore sequencing technology,and evaluate the impact of serotype quantity and sequencing time on the serotyping results,aiming to provide a method for simultaneous rapid serotyping of various Salmonella serotypes.Methods Initially,a multiplex sequencing method was established by using nanopore sequencing technology.Subsequently,a localized Salmonella serotyping workflow was developed based on the coregenome MLST database of Salmonella.Finally,the effects of serotype quantity and sequencing time on serotyping results were evaluated.Results The established method for serotyping various Salmonella serotypes achieved an accuracy and specificity of 100％,with the ability to accurately serotyping at least 6 Salmonella serotypes within 2 hours.Conclusion The multiplex nanopore sequencing method enables rapid serotyping of multiple Salmonella serotypes simultaneously,significantly improving the identification efficiency of Salmonella serotypes and providing robust support for the rapid serotyping of Salmonella serotypes in environmental water samples.

Foodborne pathogens make much difference to food safety,and troops are also at risk of infection during military operations and daily lives,so there is an urgent need for highly sensitive and rapid detection technologies.In recent years,with the continuous development of clustered regularly interspaced short palindromic repeats(CRISPR)technology,the CRISPR-Cas system with trans-cutting activity has received increasing attention.This paper outlines the basic principles of CRISPR-Cas12a-based detection technology and conventional signal readout technologies.It also analyzes the current status and developmentsof CRISPR-Cas12a in detecting foodborne pathogenic bacteria.The challenges to and prospects of this technology are also described.

Objective To investigate the effects of cinnamaldehyde,the main active component of cinnamon,on benzene-induced immune injury in mice and the related mechanism.Methods Forty male BALB/c mice were randomly divided into the control group,model group(benzene 500 mg/kg),cinnamaldehyde low,medium and high dose groups(5,25,50 mg/kg),with 8 mice in each group.Except the control group,mice in each group were treated with benzene by intragastric administration daily to induce immune and oxidative stress damage,but the intervention group was treated with cinnamaldehyde 5 times/week for 3 weeks.After medication,peripheral blood was collected 24 h after the last gavage for blood cell count,and the changes in body weight of mice in each group were observed.The pathological structure of the spleen and thymus was observed via hematoxylin-eosin(HE)staining.Peripheral blood mononuclear cells(PBMCs)of mice were extracted and the amounts of reactive oxygen species(ROS)and ATP in mitochondria were measured.Plasma levels of malondialdehyde(MDA)were measured using the barbituric acid method,the activity of glutathione peroxidase(GSH-PX)in plasmawith the dithiodinitrobenzoic acid methodand the activity of total superoxide dismutase(SOD)in plasma using the hydroxylamine method.Results After exposure to benzene,the body weight of the model group became lower(P<0.05).The spleen and thymus were damaged,and the indexes of the spleen and thymus were decreased(P<0.05).Counts of peripheral white blood cells and lymphocyteswere decreased(P<0.05).The activities of GSH and SOD in plasma were decreased(P<0.05),but the content of MDA was increased(P<0.05).The amount of mitochondrial ROS in PBMC was increased,while the ATP content was decreased(P<0.05).The weight of mice increased after treatment with cinnamaldehyde.The spleen and thymus tissues recovered well,and the indexes of the spleen and thymus were increased(P<0.05).Counts of peripheral white blood cells and lymphocytesin the high dose cinnamaldehyde group were increased(P<0.05).The activities of GSH and SOD in plasma were increased,while the content of MDA was decreased(P<0.05).The amount of mitochondrial ROS in PBMC was decreased,but the ATP content was increased(P<0.05).Treatment with cinnamaldehyde could alleviate the damage to the mitochondrial function of PBMC induced by benzene in mice,and 50 mg/kg was the best dose(P<0.05).The therapeutic effect of cinnamaldehyde had a dose-response relationship.Conclusion Cinnamaldehyde can inhibit benzene-induced immune injury and oxidative stress injury in mice by delivering an antioxidant effect and improving mitochondrial enhancement of PBMC.

Objective:To investigate the value of mammography and MRI parameters combined with red cell distribution width to lymphocyte ratio (RLR) in predicting recurrence and metastasis of breast cancer after modified radical surgery.Methods:104 female breast cancer patients who received improved radical surgery in Jiande First People’s Hospital from Jun. 2021 to Dec. 2023 were included as the study objects. The Japanese MGU-1000D MAMMOREX Pe.ru.ru DIGITAL mammography machine was used to examine each subject before surgery, and the X-ray signs of the primary tumor lesion were recorded, including maximum diameter, breast density, calcification, mass morphology, vascular signs and tumor margin. The primary tumor was evaluated by MRI using a MAGNETOM Verio magnetic resonance imaging machine and a dedicated breast examination coil, the apparent diffusion coefficient (ADC) value was measured and automatically calculated, and the RLR was recorded.Results:There were 31 patients with recurrence and metastasis and 73 patients without recurrence or metastasis. The proportion of patients with clinical stage III and Ki67 level > 14% in postoperative recurrence and metastasis group was significantly higher than that in patients without recurrence and metastasis. The proportion of patients with calcification, vascular thickening, increase and burr at the edge of mass in the recurrence and metastasis group was significantly higher than that in the patients without recurrence or metastasis. The ADC value of patients with recurrence and metastasis after breast cancer surgery was 0.93±0.12, and that of patients without recurrence and metastasis was 1.08±0.15, the former was significantly lower than the latter, and the difference was statistically significant ( t=5.64, P<0.001). The RLR of peripheral blood in patients with recurrence and metastasis after breast cancer surgery was 21.36±2.39, and that of patients without recurrence and metastasis was 19.93±2.14, the former was significantly higher than the latter, and the difference was statistically significant ( t=4.37, P<0.001). Multivariate Logistic regression analysis showed that axillary lymph node metastasis, vascularization, thickening, burr on tumor edge, small ADC value and large peripheral blood RLR were independent risk factors for recurrence and metastasis after breast cancer surgery ( P<0.05). ROC curve results showed that the area under the curve of the logistic regression model based on the above factors was 0.860 (0.798-0.921), the sensitivity was 80.4%, and the specificity was 81.8%. Conclusion:Mammogram and MRI parameters combined with peripheral blood RLR level have certain value in predicting recurrence and metastasis after modified radical breast cancer surgery.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To evaluate the effect of different reconstruction points of intrauterine applicator on the source dwell positions and plan dosimetry in intracavitary brachytherapy for cervical cancer.Methods:Clinical data of 43 patients with cervical cancer who had completed radical radiotherapy in Liuzhou Workers' Hospital from May 2020 to October 2022 were retrospectively analyzed. Among 43 patients, aged 32-79 years, 40 cases were diagnosed with squamous carcinoma and 3 cases of adenocarcinoma. All patients received external irradiation for 50.4 Gy / 28 fractions and CT-guided intracavitary brachytherapy (45° intrauterine applicator) was 36 Gy / 6 fractions. Brachytherapy was performed by using Fletcher applicator, the curvature of intrauterine applicator were 15°, 30°and45°. Two sets of brachytherapy plans were simulated for each patient. One set of plans extracted the simulated CT positioning images and the original plan of the patient's brachytherapy. The reconstruction point of the curved part of the 45° intrauterine applicator was adjusted to slice-by-slice reconstruction. The plan was optimized to meet clinical requirements according to the prescription, which was called the slice-by-slice group. In the other set of plans, slice-by-slice group was used as a template. The reconstruction points of the curved section of the 45° intrauterine applicator were adjusted to 1, 3, 5, and 7, without modifying the applicator weights and other parameters, which was called the average group 1, 3, 5 and 7. The deviation analysis of 15°, 30° and 45° intrauterine applicator with different number of reconstruction points was carried out, the reconstruction deviation of 45°, 30° and 15° intrauterine applicator at different reconstruction points was compared. Paired-sample t-test or Wilcoxon signed rank test were used to compare the differences in high-risk clinical target volume (HR-CTV) D 50%, D 90%, D 100%, V 100%, V 150%, V 200% and conformity index (CI) as well as D 2 cm3, D 1 cm3 and D 0.1 cm3 in bladder, rectum, and small intestine between two groups of 45° intrauterine applicator. Results:The reconstruction deviation in the average group was mainly from the vertical direction of the 45° intrauterine applicator. The mean reconstruction deviations of 45° (1, 3, 5, 7 reconstruction points), 30° (1, 3, 5 reconstruction points) and 15° (1, 2 reconstruction points) were 1.30 mm, 0.32 mm, 0.14 mm and 0.08 mm; 0.57 mm, 0.14 mm and 0.06 mm; 0.14 mm and 0.06 mm, respectively. There was no significant difference in the parameters of high-risk clinical target volume (HR-CTV) in the slice-by-slice group compared with the average group 5 and 7 (all P>0.005), and no significant difference was found between the average group 5 and 7 (all P>0.005). There were no statistically significant differences in bladder and rectum doses between the slice-by-slice group and the average groups or within the average groups (all P>0.005). The parameters of small intestine in the slice-by-slice group were higher than those of the average group 1, the difference was statistically significant ( P=0.002,<0.001,<0.001). The dose of small intestine in the slice-by-slice group was not statistically significant compared with those in the average group 5 and 7 (both P>0.005). The dose of small intestine in the average group 5 was not statistically significant compared with that in the average group 7 ( P>0.005). The small intestine dose deviations of D 0.1 cm3, D 1 cm3 and D 2 cm3 in the average groups at 1 reconstruction point were 2.41%±1.70%, 1.95%±1.27% and 1.71%±1.10%, respectively. Conclusion:The number of reconstruction points is recommended to be no less than 1, 3 and 5 of the curved part of the 15°, 30°and 45° Fletcher intrauterine applicator, respectively, during intracavitary brachytherapy for cervical cancer.