Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

OBJECTIVE: To evaluate the clinical outcomes and define the indications for a one-stage mandibular reconstruction technique that combines iliac bone flaps with immediate implant-based dentures, and to assess both the accuracy of surgical planning and the long-term success of the procedure. METHODS: A total of ten patients underwent the procedure at Peking University Hospital of Stomatology between June 2020 and August 2023. The preoperative biopsy pathology of all the patients confirmed a benign tumor. In this technique, iliac bone flaps were used for mandibular reconstruction, and immediate implant-based dentures were placed during the same surgical session. Various outcome measures were evaluated, including the accuracy of the surgical reconstruction, implant placement deviations (entry point, apical point, depth, and angle), and long-term outcomes, such as cervical bone resorption, implant survival, and the cumulative survival rate. RESULTS: Thirty-eight implants were successfully inserted into the iliac flaps of the ten patients. The median follow-up duration was 23.5 months, and no significant complications occurred during the follow-up period, such as infections, titanium plate exposure, implant loosening, or damage to the implants and dentures. The accuracy of preoperative virtual surgical planning (VSP) was highly reliable. The repeatability of the VSP model compared to the postoperative reconstructed mandible was as follows: 67.82% ±10.16% within 1 mm, 82.14% ±6.58% within 2 mm, and 90.61% ±4.62% within 3 mm. The average maximum deviation from the plan was (6.10±0.89) mm, with an average overall deviation of (1.14±0.31) mm. For the implants, deviations in critical parameters were as follows: entry point deviation was (2.02±0.58) mm, apical point deviation was (2.25± 0.66) mm, depth deviation was (1.26±0.51) mm, and angular deviation was 1.84°±1.10°. The implant survival rate remained 100% during the follow-up, with a cumulative survival rate of 97.37% from 1 to 4 years. Average cervical bone resorption was 0.94 mm. CONCLUSION The combination of iliac bone flaps with immediate implant-based dentures for one-stage mandibular reconstruction demonstrated pro-mising clinical outcomes, including high implant survival and minimal complications. This technique proved to be safe and reliable for mandibular reconstruction. However, further studies with larger sample sizes and longer follow-up periods are necessary to confirm the long-term efficacy and optimal indications for this procedure.
Humans ; Mandibular Reconstruction/methods* ; Male ; Ilium/surgery* ; Female ; Middle Aged ; Surgical Flaps ; Adult ; Mandible/surgery* ; Aged ; Dental Implantation, Endosseous/methods* ; Immediate Dental Implant Loading/methods* ; Bone Transplantation/methods* ; Dental Implants

OBJECTIVE: To propose a new protocol for personalized mandibular reconstruction assisted by three-dimensional (3D) retrieval model based on fully connected neural network (FCNN) and a database of mandibles, and to verify clinical feasibility of the protocol. METHODS: A database of mandibles of 300 normal northern Chinese Han people was established. On the basis of cephalometry, the mandible landmarks with good stability were further screened. Mandibular landmarks were selected and geometric features of the mandible were extracted. A 3D retrieval algorithm was developed, which could retrieve the mandible most similar to a given mandible from the database. A FCNN was built to train the algorithm to improve accuracy of the 3D retrieval model. Using Geomagic Control 2014 software, matching accuracy of the 3D retrieval model was based on aforementioned mandible database and algorithm. From December 2019 to March 2021, a total of 5 patients underwent personalized mandibular reconstruction assisted by a 3D retrieval model based on mandible database and FCNN in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. The most similar mandible was retrieved from mandible database through 3D retrieval algorithm. It was used to restore the premorbid morphology of defect area and guide mandibular reconstruction. For the 5 patients, mandible was reconstructed with iliac flap. Virtual surgical plan was transformed using individual surgical guides. RESULTS: Through screening, mandibular landmarks with high reproducibility and stability were identified and composed of mandibular landmarker protocols. After training, the average deviation between most similar mandible retrieved from the 300-case mandible database through 3D retrieval model based on FCNN and given mandible was (1.77±0.44) mm. And the root-mean-square deviation between the most similar mandible retrieved from the database and given mandible was (2.58±0.86) mm. The mandibular reconstruction surgery was successful in all the 5 patients. Their facial symmetry and occlusion were restored. All the patients were satisfied with postoperative appearance. The mean deviation between postoperative mandible and preoperative design was (0.98±0.17) mm. The area with a deviation ≤1 mm accounted for 61.34%±14. 13%, ≤2 mm accounted for 83.82%±7.35%, and ≤3 mm accounted for 93.94%± 2.87%. CONCLUSION The personalized mandibular reconstruction assisted by 3D retrieval model based on the 300-case mandible database and FCNN is feasible clinically.
Humans ; Neural Networks, Computer ; Mandibular Reconstruction/methods* ; Mandible/diagnostic imaging* ; Imaging, Three-Dimensional/methods* ; Adult ; Databases, Factual ; Female ; Male ; Algorithms ; Middle Aged ; Cephalometry

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

ObjectiveTo investigate the potential mechanism of Liangxue Tuizi Formula （凉血退紫方， LXTZF） in treating Henoch-Schönlein Purpura （HSP） by examining its regulatory effect on neutrophil extracellular trap （NETs） dysregulation via the rapidly accelerated fibrosarcoma kinase （RAF）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsSeventy Wistar rats were randomly allocated into a blank control group （n=14） and a modeling group （n=56）. Rats in the modelling group underwent an eight-week modelling period to establish HSP rat models with blood-heat syndrome via modified ovalbumin （OVA） induction method combined with oral administration of heat-property Chinese herbal medicine. Fifty successfully modeled rats were subsequently randomly divided into five groups （n=10 per group）， model group， compound glycyrrhizin group， LXTZF group， RAF inhibitor group， and LXTZF + RAF agonist group. Additionally， 10 rats were selected from the original blank control group for the final experiment. From the 11th week of modelling， rats in the blank control group and the model group received 1 ml/（100 g·d） ultrapure water via oral administration， in addition to 0.5 ml/（kg·d） 0.9% sodium chloride solution via intraperitoneal injection. The LXTZF group and the compound glycyrrhizin group received 7.5 g/（kg·d） LXTZF granule suspension via gavage， 13.5 mg/（kg·d） compound glycyrrhizin suspension via gavage， respectively. The RAF inhibitor group received 1 mg/（kg·d） GW5074 suspension via intraperitoneal injection and ultrapure water via oral administration； the LXTZF + RAF agonist group received 7.5 g/（kg·d） LXTZF granule suspension via gavage and 1 mg/（kg·d） paclitaxel suspension via intraperitoneal injection. All administrations were performed once daily for 4 weeks. After intervention， skin tissue histopathology was examined by hematoxylin and eosin （H&E） staining， immunoglobulin A （IgA） deposition was assessed via immunofluorescence， serum levels of neutrophil elastase （NE）， tumor necrosis factor-α （TNF-α）， and vascular cell adhesion molecule-1 （VCAM-1） were measured using enzyme-linked immunosorbent assay （ELISA）， serum myeloperoxidase （MPO） level was determined by a colorimetric assay； the mRNA expression levels of RAF， MEK， and ERK in skin tissue were detected by real-time quantitative polymerase chain reaction （RT-qPCR）； and the protein expression of RAF， MEK， ERK， as well as phosphorylated MEK （p-MEK） and phosphorylated ERK （p-ERK）， were analyzed by Western Blot. ResultsSkin tissue in the blank control group rats remained normal， whereas the model group exhibited neutrophil infiltration and haemorrhage with red blood cell rupture. In all drug intervention groups， neutrophil infiltration and haemorrhagic exudation reduced markedly， with LXTZF group demonstrating the most pronounced improvement. Compared with the blank control group， rats in the model group exhibited enhanced IgA fluorescence intensity in skin tissue， elevated serum levels of NE， MPO， TNF-α and VCAM-1， increased mRNA expression of RAF， MEK， ERK1 and ERK2， as well as heightened RAF protein levels and p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with the model group， the drug intervention groups exhibited reduced IgA fluorescence intensity in skin tissue， along with decreased serum levels of NE， MPO， TNF-α， and VCAM-1 （P＜0.05）. In LXTZF group and RAF inhibition groups， reduced mRNA expression of RAF， MEK， ERK1， and ERK2 was observed in rat skin tissue， alongside decreased RAF protein levels and reduced p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with LXTZF + RAF agonist group， the compound glycyrrhizin group， LXTZF group， and RAF inhibitior group exhibited reduced IgA fluorescence intensity in skin tissue， decreased serum NE， MPO， TNF-α， and VCAM-1 levels， and decreased MEK mRNA expression and p-MEK/MEK ratio （P＜0.05）. ConclusionThe potential mechanism by which LXTZF treats Henoch-Schönlein purpura with blood heat syndrome may involve blocking the RAF/MEK/ERK signaling pathway in skin tissue， and suppressing excessive formation of NETs， thereby reducing IgA deposition in dermal microvessels and attenuating systemic inflammatory responses.

Non-small cell lung cancer(NSCLC)is a prevalent and aggressive global malignancy.Conventional sur-gical treatments,radiotherapy,chemotherapy,and targeted therapies often fall short in halting disease progression due to inher-ent limitations,resulting in suboptimal prognosis.Despite the advent of immunotherapy drugs offering new hope for NSCLC treatment,current efficacy remains insufficient to meet all patient needs.Therefore,actively exploring novel immunotherapeu-tic approaches to further reduce mortality rates in NSCLC patients has become a crucial focus of NSCLC research.This article aims to systematically review the anti-tumor effects ofinterleukin-21 and follicular helper T cells in NSCLC immunotherapy by summarizing and analyzing relevant literatures from both domestic and international sources,as well as exploring the potential for enhancing NSCLC treatment prospects through immune checkpoint regulation via immunotherapeutic means.

With the development of information technology and the increasing demand for vaccination services among the people, it is a definite trend to enhance the quality of vaccination services through digitization. This article starts with a clear concept of digital services for vaccination, introduces the current development status in China and abroad, analyzes the advantages and disadvantages of existing models in leading regions, takes a glean from the summation, and proposes targeted solutions. This study suggests establishing a departmental coordination mechanism for data interconnection and sharing, formulating data standards and functional specifications, enhancing the functionalities of the immunization planning information system, strengthening data collection and analytical usage, and intensifying appointment management and science and health education to provide expert guidance for the construction of digital vaccination services across the country in the future.

Objective To establish a nomogram model for efficiently predicting overall survival(OS)and cancer-specific survival(CSS)in patients with CRCHBM.Method 2239 patients from 2010 to 2019 were retrospectively analyzed from the Surveillance,Epidemiology,and End Results Program(SEER)databases and Wuhan Union Hospital Cancer Center.SEER is randomly assigned to the training and internal validation cohorts,and the Wuhan database serves as the external validation.Cox regression analyses were used to determine the independent clinicopathological prognosis factors affecting OS and CSS,and a nomogram was constructed to predict OS and CSS.The clinical utility of columnar plots was assessed using calibration curves,area under the curve(AUC),and decision curve analysis(DCA).Result OS column line graphs were constructed based on nine independent predictors:age,tumor location,degree of differentiation,tumor size,TNM stage,chemotherapy,primary focus surgery,number of lymph nodes sampled,and serum carcinoembryonic antigen(CEA)level.The C-index of the nomogram to predict the 1-,3-,and 5-year OS were 0.764,0.790,and 0.805 in the training group,0.754,0.760,and 0.801 in the internal validation group,and 0.822,0.874,and 0.906 in the external validation group.CSS column line graphs were constructed based on 3 independent predictors of TNM staging,radiotherapy and chemotherapy.The 1-,3-,and 5-year CSS AUROC values of the training group were 0.791,0.757,and 0.782,respectively.0.682,0.709,0.625 in the internal validation group and 0.759,0.702,0.755 in the external validation group,respectively.The results of receiver operating characteristic curve(ROC),ROC and DCA showed that the use of our model was more effective in predicting OS and CSS than other single clinicopathological features.Conclusion In summary,the nomogram based on significant clinicopathological features can be conveniently used to predict OS and CSS individually in patients with CRCHBM.

With the development of information technology and the increasing demand for vaccination services among the people, it is a definite trend to enhance the quality of vaccination services through digitization. This article starts with a clear concept of digital services for vaccination, introduces the current development status in China and abroad, analyzes the advantages and disadvantages of existing models in leading regions, takes a glean from the summation, and proposes targeted solutions. This study suggests establishing a departmental coordination mechanism for data interconnection and sharing, formulating data standards and functional specifications, enhancing the functionalities of the immunization planning information system, strengthening data collection and analytical usage, and intensifying appointment management and science and health education to provide expert guidance for the construction of digital vaccination services across the country in the future.