Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective This study analyzes the risk points in the quality control of bioink and the main processes of bioprinting,clarifies and explores the quality control and supervision model for bioprinting medical devices,and provides theoretical and practical guidance to ensure the safety and effectiveness of bioprinting medical devices.Methods The quality control risk points throughout the bioprinting process were comprehensively analyzed,with a particular focus on bioprinting materials and key processes.The regulatory model and methods for bioprinting medical devices were examined.This research concentrated on critical technologies such as extrusion,laser-assisted,and in situ bioprinting,assessing their potential for clinical applications and regulatory challenges.Results Bioink from different sources should meet regulatory requirements.It is essential to ensure aseptic handling of raw materials and to validate sterilization under"worst-case"conditions.Conclusion As bioprinting technology advances rapidly,corresponding research into materials,processes,and quality risk control should be conducted to ensure the concurrent development of the regulatory system.This will continuously contribute to the orderly progression of the entire industry and human health.

Bladder cancer （BCa） is the most common malignant tumor of the urinary system， and its incidence is increasing year by year. At present， for all patients with resectable non-metastatic muscle-invasive BCa， radical cystectomy + bilateral pelvic lymph node dissection is strongly recommended， but they still face the risk of recurrence， metastasis and death. In recent years， the proportion of patients with advanced and metastatic BCa is increasing among patients with newly diagnosed BCa. Although current treatment models are diverse， they often struggle to achieve significant efficacy due to their low effectiveness and adverse effects， resulting in low survival rates for patients with advanced and metastatic BCa. Therefore， the treatment of BCa still faces great challenges， and there is an urgent need to discover an effective new antitumor drug. With the improvement of medical standards， traditional Chinese medicine has shown great advantages in the treatment of BCa. Traditional Chinese medicine is mild and easy to accept， and can inhibit tumor progression through a multi-pathway， multi-way and multi-target manner， so as to exert its anticancer effect. Taraxaci Herba is a medicinal and food homologous plant， which has many biological activities， such as antibacterial， anti-inflammatory， anti-oxidation， anti-tumor， protecting liver and gallbladder， reducing blood sugar and enhancing immunity， and it has shown a clear anticancer effect in breast cancer， liver cancer， gastric cancer， tongue cancer and lung cancer. By reviewing previous studies worldwide， this article summarizes the mechanism of Taraxaci Herba extract in inducing autophagy and apoptosis， inhibiting cell migration and invasion， regulating cell cycle and proliferation， regulating cell metabolism， inhibiting tumor angiogenesis， combining the effects of chemotherapeutic drugs， and regulating the transduction of related signal pathways. On this basis， this study systematically elaborates on the potential mechanism of Taraxaci Herba against BCa， in order to provide a theoretical basis for the research and treatment of BCa.

This study was aimed at creating an engineered strain of Bacillus subtilis for efficient expression of biologically active type 2 toxin B(TcdB2)derived from a highly virulent strain of Clostridium difficile.The TcdB2 gene was cloned from ST1/RT027 strain genome DNA,incorporated into the PHT01 vector,and then transformed into B.subtilis strain WB800N for prokaryotic expression.Cell toxicity assays revealed that the recombinant TcdB2 exhibited cytotoxic effects in various cells.The engineered B.subtilis strain effectively expressed biologically active TcdB2,thus providing a basis for further exploration of the pathogenic mechanisms of highly virulent strains of C.difficile and establishing a foundation for potential vaccine can-didate targets.

Objective:To explore the application of three-dimensional measurement data in the diagnosis and treatment of mandibular angle prominent in Shanghai female youth.Methods:The young females in Shanghai were selected from the Clinical Database of Shanghai Universal Medical Imaging Diagnostic Center in Xuhui and the Second Affiliated Hospital of Naval Medical University from January 2010 to December 2020. Three-dimensional reconstruction of the craniofacial region was performed using computer-aided technology, and the subjects were divided into prominent group, attractive group, and contrast group according to the three-dimensional reconstruction images and doctor’s evaluation results. The mandibular and facial regions of the three groups were measured in three dimensions. The measurement indicators included bone tissue indicators such as mandibular angle (∠Co-Go-Me), mandibular expansion angle (∠Go-Me-Go), mandibular body length/mandibular support height ratio (Go-Me/Co-Go), mandibular angle width/zygomatic width ratio (Go-Go/Zy-Zy), and mandibular width index (Go-Go/Co-Co); and the soft tissue indicators included mandibular angle (∠t-go’-gn), mandibular angle width/midface width ratio (go’-go’/zy’-zy’), and mandibular angle width/mandibular height ratio (go’-go’/s-gn). The data were analyzed using SPSS 18.0 software, with normally distributed metric data expressed as Mean±SD. One-way analysis of variance or Kruskal-Wallis rank sum test was used to compare the three groups, and LSD method was used for comparison among prominent group, contrast group and attractive group. Fisher discriminant analysis was used for indicators with statistical significance. P<0.05 was considered statistically significant. Results:A total of 200 young females in Shanghai were enrolled in this study. 73 cases were included in the prominent group, with an age of (26.1±3.2) years, body weight of (54.3±4.3) kg, and body mass index(BMI) of (21.3±1.9) kg/m 2; 32 cases in the attractive group, with an age of (25.3±3.1) years, body weight of (58.7±3.7) kg, and BMI of (20.0±1.5) kg/m 2; and 95 cases in the contrast group, with an age of (27.2±3.7) years, body weight of (53.3±3.4) kg, and BMI of (20.1±1.3) kg/m 2. There were no significant differences in age, body weight, and BMI among the three groups ( P>0.05). There were significant differences in the measurement values of indicators such as ∠Co-Go-Me, ∠Go-Me-Go, Go-Me/Co-Go, Go-Go/Co-Co, ∠t-go’-gn among the three groups ( P<0.01). The prominent group showed significant outward and posterior protrusion in the mandibular angle area compared with the contrast group in terms of ∠Co-Go-Me (111.69°±4.19° vs. 115.43°±3.01°), ∠Go-Me-Go (66.27°±4.51° vs. 64.19°±3.69°), and ∠t-go’-gn (126.13°±7.51° vs. 130.34°±7.21°) ( P<0.01). The attractive group showed significant differences compared with the contrast group in terms of ∠Co-Go-Me (121.61°±3.22° vs. 115.43°±3.01°), Go-Me/Co-Go (1.67±0.20 vs. 1.58±0.15), and ∠t-go’-gn (137.17°±7.57° vs. 130.34°±7.21°) ( P<0.01). The lower quartile of ∠Co-Go-Me in the prominent group was 110°, and the upper quartile of ∠GO-Me-Go was 72°, with a small overlap in the mode region compared with the other two groups. Three indicators, ∠Co-Go-Me ( D1), ∠Go-Me-Go ( D2), and Go-Me/Co-Go ( D3), were selected to establish Fisher discriminant functions. The Fisher discriminant function for prominent group was Z=0.237 D2-0.084 D1-5.813, with a discriminant rate of 60.3%, and for the attractive group was Z=0.257 D1-0.015 D3-28.610, with a Fisher discriminant rate of 85.3%. Conclusion:The ∠Co-Go-Me, ∠Go-Me-Go, ∠t-go’-gn, and other data in Shanghai female youth can be used to evaluate their mandibular contour morphology, providing a reference for the diagnosis and treatment of mandibular angle prominent. The ∠Co-Go-Me of the mandibular aesthetic group should approach 122°, and ∠Co-Go-Me<110° and ∠Go-Me-Go>72° can be used as preliminary indicators for the diagnosis of mandibular angle prominent in prominent group, guiding clinical practice.

Objective:To use the least square method to curve fit the mandibular contours of Chinese women, obtain an ideal fitting function model, and explore the effectiveness of using mathematical curves for bone cutting line design in mandibular osteotomy.Methods:(1) Female cranial CT data were selected from the Second Affiliated Hospital of Naval Medical University and Shanghai Universal Medical Imaging Diagnostic Center. The mandibular morphology of the CT reconstructed images was evaluated using the Likert scale, and samples were selected from individuals with mandibular angle hypertrophy, aesthetically pleasing mandibular morphology, and aesthetically pleasing appearance after osteotomy as references. The Python platform Spyder module was used to analyze the curve fitting of mandibular contour morphology and the goodness of fitting was measured by the coefficient of determination R2( R2 ≥ 0.800 was considered acceptable for the fitted function, while R2≥ 0.900 was deemed sufficient to meet clinical application requirements). The fitting degree of polynomial functions, logarithmic functions, and other mathematical curves in the facial contours of individuals with aesthetically pleasing mandibular morphology were analyzed to obtain an ideal mandibular contour curve fitting function model. (2) Patients with mandibular angle hypertrophy who underwent intraoral mandibular osteotomy from March 2020 to March 2021 at the Department of Plastic and Reconstructive Surgery of Second Affiliated Hospital of Naval Medical University were divided into a mathematical template group (guided by a mathematical curve-based bone cutting plan), a traditional template group (guided by traditional bone cutting templates), and a manual osteotomy group. Three-dimensional reconstruction technology was used to evaluate the efficacy postoperatively. Preoperative preparation time, bone cutting time, surgical time, and postoperative complications were compared among the three groups. Patient self-evaluation of surgical outcomes was assessed using the jawline component of the Face-Q questionnaire. Results:(1) A total of 205 female cranial CT data were selected, including 73 cases of mandibular angle hypertrophy, 32 cases of aesthetically pleasing mandibular morphology, and 5 cases of aesthetically pleasing appearance after osteotomy as reference samples for mandibular contour curve fitting. The result showed that the third-degree polynomial function ( R2=0.918±0.027) and logarithmic function ( R2=0.930±0.039) could be used to simulate the mandibular contour morphology in individuals with aesthetically pleasing mandibular morphology. (2) The mathematical template group (using logarithmic function for bone cutting design), traditional template group, and manual osteotomy group included 28, 14, and 11 patients with mandibular angle hypertrophy, respectively. All patients were satisfied with the postoperative mandibular contour morphology and no complications such as deformity or significant asymmetry were observed. The mathematical template group outperformed the manual osteotomy group in terms of the total score of the jawline questionnaire, surgical time, and bone cutting time(all P<0.01). The preoperative preparation time in the mathematical template group was shorter than that in the traditional template group [(82.39±9.77) min vs. (97.07±17.49) min, P<0.01], and the jawline questionnaire evaluation showed that the patients in the mathematical template group had higher scores in evaluating the lateral view of the mandible and the smoothness of the lower facial contour compared to the traditional template group [3.75±0.44 vs. 3.14±0.36, 3.71±0.46 vs. 3.36±0.50, both P<0.05]. Conclusion:Curve fitting based on the least square method can be used to simulate mandibular angle osteotomy. Models such as logarithmic functions can be used for preoperative design of mandibular osteotomy and have advantages in terms of contour smoothness and symmetry after surgery. Bone cutting design based on mathematical curves can meet patient demands and aesthetic standards, providing precise and individualized solutions for surgery.

Objective:To explore the application of three-dimensional measurement data in the diagnosis and treatment of mandibular angle prominent in Shanghai female youth.Methods:The young females in Shanghai were selected from the Clinical Database of Shanghai Universal Medical Imaging Diagnostic Center in Xuhui and the Second Affiliated Hospital of Naval Medical University from January 2010 to December 2020. Three-dimensional reconstruction of the craniofacial region was performed using computer-aided technology, and the subjects were divided into prominent group, attractive group, and contrast group according to the three-dimensional reconstruction images and doctor’s evaluation results. The mandibular and facial regions of the three groups were measured in three dimensions. The measurement indicators included bone tissue indicators such as mandibular angle (∠Co-Go-Me), mandibular expansion angle (∠Go-Me-Go), mandibular body length/mandibular support height ratio (Go-Me/Co-Go), mandibular angle width/zygomatic width ratio (Go-Go/Zy-Zy), and mandibular width index (Go-Go/Co-Co); and the soft tissue indicators included mandibular angle (∠t-go’-gn), mandibular angle width/midface width ratio (go’-go’/zy’-zy’), and mandibular angle width/mandibular height ratio (go’-go’/s-gn). The data were analyzed using SPSS 18.0 software, with normally distributed metric data expressed as Mean±SD. One-way analysis of variance or Kruskal-Wallis rank sum test was used to compare the three groups, and LSD method was used for comparison among prominent group, contrast group and attractive group. Fisher discriminant analysis was used for indicators with statistical significance. P<0.05 was considered statistically significant. Results:A total of 200 young females in Shanghai were enrolled in this study. 73 cases were included in the prominent group, with an age of (26.1±3.2) years, body weight of (54.3±4.3) kg, and body mass index(BMI) of (21.3±1.9) kg/m 2; 32 cases in the attractive group, with an age of (25.3±3.1) years, body weight of (58.7±3.7) kg, and BMI of (20.0±1.5) kg/m 2; and 95 cases in the contrast group, with an age of (27.2±3.7) years, body weight of (53.3±3.4) kg, and BMI of (20.1±1.3) kg/m 2. There were no significant differences in age, body weight, and BMI among the three groups ( P>0.05). There were significant differences in the measurement values of indicators such as ∠Co-Go-Me, ∠Go-Me-Go, Go-Me/Co-Go, Go-Go/Co-Co, ∠t-go’-gn among the three groups ( P<0.01). The prominent group showed significant outward and posterior protrusion in the mandibular angle area compared with the contrast group in terms of ∠Co-Go-Me (111.69°±4.19° vs. 115.43°±3.01°), ∠Go-Me-Go (66.27°±4.51° vs. 64.19°±3.69°), and ∠t-go’-gn (126.13°±7.51° vs. 130.34°±7.21°) ( P<0.01). The attractive group showed significant differences compared with the contrast group in terms of ∠Co-Go-Me (121.61°±3.22° vs. 115.43°±3.01°), Go-Me/Co-Go (1.67±0.20 vs. 1.58±0.15), and ∠t-go’-gn (137.17°±7.57° vs. 130.34°±7.21°) ( P<0.01). The lower quartile of ∠Co-Go-Me in the prominent group was 110°, and the upper quartile of ∠GO-Me-Go was 72°, with a small overlap in the mode region compared with the other two groups. Three indicators, ∠Co-Go-Me ( D1), ∠Go-Me-Go ( D2), and Go-Me/Co-Go ( D3), were selected to establish Fisher discriminant functions. The Fisher discriminant function for prominent group was Z=0.237 D2-0.084 D1-5.813, with a discriminant rate of 60.3%, and for the attractive group was Z=0.257 D1-0.015 D3-28.610, with a Fisher discriminant rate of 85.3%. Conclusion:The ∠Co-Go-Me, ∠Go-Me-Go, ∠t-go’-gn, and other data in Shanghai female youth can be used to evaluate their mandibular contour morphology, providing a reference for the diagnosis and treatment of mandibular angle prominent. The ∠Co-Go-Me of the mandibular aesthetic group should approach 122°, and ∠Co-Go-Me<110° and ∠Go-Me-Go>72° can be used as preliminary indicators for the diagnosis of mandibular angle prominent in prominent group, guiding clinical practice.

Objective:To use the least square method to curve fit the mandibular contours of Chinese women, obtain an ideal fitting function model, and explore the effectiveness of using mathematical curves for bone cutting line design in mandibular osteotomy.Methods:(1) Female cranial CT data were selected from the Second Affiliated Hospital of Naval Medical University and Shanghai Universal Medical Imaging Diagnostic Center. The mandibular morphology of the CT reconstructed images was evaluated using the Likert scale, and samples were selected from individuals with mandibular angle hypertrophy, aesthetically pleasing mandibular morphology, and aesthetically pleasing appearance after osteotomy as references. The Python platform Spyder module was used to analyze the curve fitting of mandibular contour morphology and the goodness of fitting was measured by the coefficient of determination R2( R2 ≥ 0.800 was considered acceptable for the fitted function, while R2≥ 0.900 was deemed sufficient to meet clinical application requirements). The fitting degree of polynomial functions, logarithmic functions, and other mathematical curves in the facial contours of individuals with aesthetically pleasing mandibular morphology were analyzed to obtain an ideal mandibular contour curve fitting function model. (2) Patients with mandibular angle hypertrophy who underwent intraoral mandibular osteotomy from March 2020 to March 2021 at the Department of Plastic and Reconstructive Surgery of Second Affiliated Hospital of Naval Medical University were divided into a mathematical template group (guided by a mathematical curve-based bone cutting plan), a traditional template group (guided by traditional bone cutting templates), and a manual osteotomy group. Three-dimensional reconstruction technology was used to evaluate the efficacy postoperatively. Preoperative preparation time, bone cutting time, surgical time, and postoperative complications were compared among the three groups. Patient self-evaluation of surgical outcomes was assessed using the jawline component of the Face-Q questionnaire. Results:(1) A total of 205 female cranial CT data were selected, including 73 cases of mandibular angle hypertrophy, 32 cases of aesthetically pleasing mandibular morphology, and 5 cases of aesthetically pleasing appearance after osteotomy as reference samples for mandibular contour curve fitting. The result showed that the third-degree polynomial function ( R2=0.918±0.027) and logarithmic function ( R2=0.930±0.039) could be used to simulate the mandibular contour morphology in individuals with aesthetically pleasing mandibular morphology. (2) The mathematical template group (using logarithmic function for bone cutting design), traditional template group, and manual osteotomy group included 28, 14, and 11 patients with mandibular angle hypertrophy, respectively. All patients were satisfied with the postoperative mandibular contour morphology and no complications such as deformity or significant asymmetry were observed. The mathematical template group outperformed the manual osteotomy group in terms of the total score of the jawline questionnaire, surgical time, and bone cutting time(all P<0.01). The preoperative preparation time in the mathematical template group was shorter than that in the traditional template group [(82.39±9.77) min vs. (97.07±17.49) min, P<0.01], and the jawline questionnaire evaluation showed that the patients in the mathematical template group had higher scores in evaluating the lateral view of the mandible and the smoothness of the lower facial contour compared to the traditional template group [3.75±0.44 vs. 3.14±0.36, 3.71±0.46 vs. 3.36±0.50, both P<0.05]. Conclusion:Curve fitting based on the least square method can be used to simulate mandibular angle osteotomy. Models such as logarithmic functions can be used for preoperative design of mandibular osteotomy and have advantages in terms of contour smoothness and symmetry after surgery. Bone cutting design based on mathematical curves can meet patient demands and aesthetic standards, providing precise and individualized solutions for surgery.

This paper makes an interpretation of the collection Acupuncture: how to improve the evidence base published by BMJ & BMJ Open. Studies show that the quality of randomized controlled trial (RCT) of acupuncture is low, and multivariable Meta-regression analysis fails to confirm most factors commonly believed to influence the effect of acupuncture. The methodological challenges in design and conduct of RCT in acupuncture were analyzed, and a consensus on how to design high-quality acupuncture RCT was developed. The number of acupuncture systematic reviews was huge but the evidence was underused in clinical practice and health policy, and a large number of western clinical practice guidelines recommended acupuncture therapy, but the usefulness of recommendations needed to be improved. In view of the problems in clinical research on acupuncture mentioned in this collection, combined with the analysis of the purpose of clinical research on acupuncture, perspectives, study types, as well as the relationship between evidence and clinical decision-making, a five-stage study paradigm of clinical research on acupuncture is proposed.
Acupuncture Therapy ; Acupuncture ; Research Design ; Consensus

Metastatic pheochromocytoma and paraganglioma(MPPGL)is a rare neuroendocrine tumour in which genetic factors play an important role.In recent years,with the continuous progress of genetic testing technol-ogy,more and more susceptibility genes have been proved to be associated with MPPGL,making early identifica-tion of MPPGL possible.Recent studies have shown that genes associated with the development of MPPGL include SDHA,SDHB,SDHC,SDHD,SDHAF2,FH,MDH2,VHL,IDH1,PDH1/2,SLC25A11,GOT2,DLST,CSDE1,MAML3,H3F3A,MERTK,PCDHGC3,and KIF1B,with SDHA,SDHB,SDHC,SDHD,and SDHAF2 being the common pathogenic genes.Potential mutations affect the clinical manifestations of MPPGL,such as malignant potential and genetic prediction,which can help to better understand the clinical course and treat accordingly.Genetic testing for pheochromocytomas and paragangliomas allows for early detection of genetic syndromes and facilitates close follow-up of high-risk patients.This article provides a review of the progress of research on susceptibility genes identified in MPPGL in recent years,with a view to providing a certain theoretical basis for further related research.