ObjectiveTo investigate the effects of Yishen Juanbi pills （YSJB）-containing bone marrow fluid on the migration and differentiation phenotypes of CD4⁺T lymphocytes based on the stromal cell-derived factor-1/chemokine receptor 4 （SDF-1/CXCR4） signaling pathway. MethodsPrimary CD4⁺T lymphocytes were isolated from mice using magnetic bead separation and identified for purity by flow cytometry. A CD4⁺T lymphocyte culture system was then established to observe the effects of SDF-1 on CD4⁺T-cell migration and differentiation. On this basis， the experimental groups included the Sham group， the ovariectomy （OVX） group， the Sham+collagen-induced arthritis （CIA） group， the OVX+CIA group， the Sham+CIA+YSJB group （2.16 g·kg^-1）， the OVX+CIA+YSJB group （2.16 g·kg^-1）， and the OVX+CIA+methotrexate （MTX） group （1.5 mg·kg^-1）. Bone marrow fluid from each group was prepared according to previous methods and added to the CD4⁺ T-cell culture system at 5% （v/v）. Transwell assays were used to examine CD4⁺T-cell migration in each group. Real-time PCR was used to measure the mRNA expression levels of interleukin （IL）-17， tumor necrosis factor-α （TNF-α）， retinoic-acid-related orphan receptor γt （RORγt）， IL-10， transforming growth factor-β （TGF-β）， forkhead box P3 （FoxP3）， CXCR4， phosphoinositide 3-kinase （PI3K）， and protein kinase B （Akt）. Western blot was used to detect the expression of helper T （Th）17/regulatory T （Treg） cell signature factors （RORγt， FoxP3）， CXCR4， PI3K， phosphorylated （p）-PI3K， Akt， and p-Akt. In a separate set of experiments， cells were divided into the Sham group， OVX+CIA group， OVX+CIA+CXCR4 antagonist AMD3100 group， and OVX+CIA+YSJB+AMD3100 group to observe changes in the above indicators following AMD3100 intervention. ResultsCompared with the Sham group， the number of migrated cells in the lower chamber was significantly increased in the Sham+CIA and OVX+CIA groups （P<0.05， P<0.01）. The mRNA expression of RORγt， IL-17， TNF-α， CXCR4， PI3K， and Akt was significantly upregulated， whereas FoxP3， IL-10， and TGF-β mRNA expression was significantly decreased （P<0.05， P<0.01）. Protein expression of RORγt， CXCR4， p-PI3K/PI3K， and p-Akt/Akt was significantly increased， while FoxP3 protein expression was markedly decreased （P<0.05， P<0.01）. Compared with the OVX+CIA group， the OVX+CIA+YSJB group and OVX+CIA+MTX group showed significantly reduced migration （P<0.05）， mRNA expression of RORγt， IL-17， TNF-α， CXCR4， PI3K， and Akt was also significantly decreased， while FoxP3， IL-10， and TGF-β mRNA expression was significantly increased （P<0.05， P<0.01）. RORγt protein expression was significantly downregulated， and FoxP3 protein expression markedly upregulated （P<0.05）. In the OVX+CIA+YSJB group， CXCR4， p-PI3K/PI3K， and p-Akt/Akt protein expression was significantly decreased （P<0.05）. Compared with the OVX+CIA group， RORγt， CXCR4， PI3K， and Akt mRNA expression in CD4⁺T cells was significantly decreased in the OVX+CIA+AMD3100 group and the OVX+CIA+YSJB+AMD3100 group， while FoxP3 mRNA and protein expression was significantly upregulated （P<0.05， P<0.01）. RORγt， CXCR4， p-PI3K/PI3K， and p-Akt/Akt protein expression was also markedly decreased （P<0.05， P<0.01）. Compared with the OVX+CIA+AMD3100 group， the OVX+CIA+YSJB+AMD3100 group showed significantly decreased RORγt and Akt mRNA expression （P<0.05） and significantly lower p-Akt/Akt protein expression （P<0.05）. ConclusionYSJB-containing bone marrow fluid suppresses CD4⁺T-cell migration and regulates Th17/Treg balance by downregulating Th17-associated signature factors and upregulating Treg-associated signature factors through inhibition of the SDF-1/CXCR4 signaling pathway and PI3K/Akt signaling pathway. The SDF-1/CXCR4 signaling pathway is one of the targets through which YSJB inhibits CD4⁺T-cell differentiation.

The Pharmacovigilance Guideline for Clinical Application of Chinese Patent Medicine for External Use （T/CACM 1563.5—2024）， the first guideline in China specializing for the clinical safety of Chinese patent medicines for external use， was led by the Institute of Basic Research in Clinical Medicine，China Academy of Chinese Medical Sciences，and jointly developed by more than 30 research institutions of medical sciences across the country. Aiming to standardize the pharmacovigilance activities in the clinical application of Chinese patent medicines for external use，the guideline systematically categorizes potential risks and proposes prevention and control measures that cover 11 core sections of risk monitoring and reporting， signal identification，as well as assessment and control， addressing the gap in domestic and international standardization of this field. The compilation of this guideline strictly adhered to international norms and domestic regulations， involving multiple rounds of expert consultations，hybrid interviews， and evidence integration （covering literature，medical insurance，essential medicine，pharmacopoeia data， and regulatory information）. With the scope of application defined to include medical institutions， pharmaceutical manufacturers and distribution enterprises，as well as regulatory authorities， the guideline focuses on key issues such as inherent medicine risks，quality risks，off-label use，risks of combination therapy，and the safety in special populations. During the compilation，core discrepancies such as the definition of application scope and quality risk control were addressed to ensure alignment with regulations such as the Drug Administration Law of the People's Republic of China and the Good Pharmacovigilance Practice. The guideline is registered internationally （PREPARE—2022CN463）. In the future，the implementation of the guideline will be promoted through hierarchical dissemination，dynamic revision，and post-effectiveness evaluation， contributing to rational clinical use and improved patient safety.

The Pharmacovigilance Guideline for Clinical Application of Chinese Patent Medicine for External Use （T/CACM 1563.5—2024）， the first guideline in China specializing for the clinical safety of Chinese patent medicines for external use， was led by the Institute of Basic Research in Clinical Medicine，China Academy of Chinese Medical Sciences，and jointly developed by more than 30 research institutions of medical sciences across the country. Aiming to standardize the pharmacovigilance activities in the clinical application of Chinese patent medicines for external use，the guideline systematically categorizes potential risks and proposes prevention and control measures that cover 11 core sections of risk monitoring and reporting， signal identification，as well as assessment and control， addressing the gap in domestic and international standardization of this field. The compilation of this guideline strictly adhered to international norms and domestic regulations， involving multiple rounds of expert consultations，hybrid interviews， and evidence integration （covering literature，medical insurance，essential medicine，pharmacopoeia data， and regulatory information）. With the scope of application defined to include medical institutions， pharmaceutical manufacturers and distribution enterprises，as well as regulatory authorities， the guideline focuses on key issues such as inherent medicine risks，quality risks，off-label use，risks of combination therapy，and the safety in special populations. During the compilation，core discrepancies such as the definition of application scope and quality risk control were addressed to ensure alignment with regulations such as the Drug Administration Law of the People's Republic of China and the Good Pharmacovigilance Practice. The guideline is registered internationally （PREPARE—2022CN463）. In the future，the implementation of the guideline will be promoted through hierarchical dissemination，dynamic revision，and post-effectiveness evaluation， contributing to rational clinical use and improved patient safety.

OBJECTIVES: In the early stage of central cervical disc herniation, clinical symptoms may be mild. However, as the spinal cord becomes compressed by herniated nucleus pulposus tissue, progressive edema and degeneration may occur, resulting in more severe clinical manifestations, including limb weakness, bladder and bowel dysfunction, spastic paraplegia of the lower extremities, and even respiratory difficulty. The spinal endoscopic Key-hole technique is widely applied in treating radiculopathic cervical spondylosis and has demonstrated good clinical outcomes. This study aims to analyze and summarize the technical points and therapeutic efficacy of the far lateral Key-hole technique in the treatment of central cervical disc herniation, providing reference for clinical application. METHODS: Eight patients with central cervical disc herniation treated with the far lateral Key-hole technique were included as the experimental group. Another 8 patients who underwent single-level anterior cervical diskectomy and fusion (ACDF) during the same period were selected as the control group. Data collected included gender, age, intraoperative blood loss, incision length, and length of hospitalization. Pain severity was evaluated using the Visual Analogue Scale (VAS); cervical function was assessed using the Japanese Orthopaedic Association (JOA) score; and cervical disability was measured by the neck disability index (NDI). Radiological outcomes were assessed using disc height index (DHI), cervical Cobb angle, and operative segment Cobb angle. RESULTS: Compared with the control group, the experimental group had significantly less intraoperative blood loss, shorter incision length, and shorter hospital stay (all P<0.05), while there was no significant difference in operation time (P>0.05). Postoperative VAS and NDI scores in both groups were significantly lower than preoperative values, and JOA scores significantly improved (P<0.05). No significant differences were noted between the two groups preoperatively (P>0.05). Postoperatively, the experimental group showed significantly lower VAS and NDI scores and higher JOA scores than the control group (P<0.05). There was no statistical significance in DHI before and after surgery in the experimental group (P>0.05), while the DHI increased significantly postoperatively in the control group (P<0.05). Postoperative DHI in the experimental group was significantly lower than in the control group (P<0.05). No significant differences were observed in the cervical Cobb angle either within or between groups (all P>0.05). The operative segment Cobb angle increased significantly after surgery in the control group (P<0.05), while no other operative segment angle changes were statistically significant (all P>0.05). CONCLUSIONS The far lateral Key-hole technique offers advantages in treating central cervical disc herniation, including reduced intraoperative bleeding, smaller incision length, shorter hospitalization, and improved postoperative pain relief. Additionally, the technique does not affect cervical physiological curvature or stability in the short term, making it suitable for clinical application.
Humans ; Intervertebral Disc Displacement/surgery* ; Cervical Vertebrae/surgery* ; Male ; Female ; Middle Aged ; Adult ; Diskectomy/methods* ; Treatment Outcome ; Spinal Fusion/methods* ; Endoscopy/methods*

Stroke is an acute cerebrovascular disease with high morbidity,disability and mortality.It has a rapid onset,multifarious morbidity and complex pathogenesis,with phlegm representing as an important pathogenic factor.The treatment of the acute phase of stroke is of paramount importance in determining the prognosis of patients.The method of eliminating phlegm and opening the orifices represents a pivotal approach within the domain of Chinese medicine for the treatment of the acute phase of stroke.Moreover,contemporary medical science has corroborated the efficacy of this method through the examination of its applications from a multitude of perspectives.In this paper,the theoretical basis of the method of eliminating phlegm and opening the orifices is elaborated in depth,and the mechanism and clinical application of this method in the acute phase of stroke,such as phlegm-heat and visceral solidity,phlegm-fire stasis,wind-phlegm obstruction,and phlegm-stasis inter-conjugation,are summarized in detail,with a view to providing references to the clinical treatments.

Approximately 300 million tons of plastic are produced globally each year,which has a serious impact on human health,marine life and the livestock industry.Microplastics have also been detected in meat and milk samples.Research has shown that nanoplastics(NP)(＜1 μm)and mi-croplastics(MP)(1 μm-5 mm)can affect the digestive,immune and reproductive systems of ani-mals.This experiment aims to investigate whether NP and MP regulate autophagy and damage the nervous system and spatial memory of animals.This experiment was divided into control group,nanoplastic group(PS-NP group,0.1 μm)and microplastic group(PS-MP group,1 μm),with 20 mice in each group.The mice were given 0.5 mL of PS-NP and PS-MP every day for 35 consecutive days,followed by neck amputation and brain analysis.The results showed that NPs and MPs of dif-ferent diameters caused varying degrees of damage to the brains of mice.In the behavioral tests of new object recognition,barnes maze and Y-shaped maze spatial memory,compared with the control group,the PS-NP group and PS-MP group showed a significant decrease in spatial memory ability of mice.HE staining results showed that neuronal cells in the PS-NP and PS-MP groups of mice exhibited shrinkage,decreased cell volume and deepened staining.The number of Nissl bodies de-creased,leading to dissolution and disappearance.RT-PCR and Western blot results showed that compared with the control group,the expression of glutamate receptors NR1,NR2A and NR2B in-creased in mice administered NP and MP orally,while the expression of autophagy related proteins Parkin,LC3B and Beclin1 was inhibited.In summary,this study suggests that nanoplastics and mi-croplastics stimulate glutamate receptors in mice by inhibiting the autophagy pathway,leading to impaired spatial memory.

Objective To discuss the method of constructing TCM word network and the subsequent optimization method;To solve the problems of natural language processing in the TCM-clinical decision support system using TCM terminology.Methods This study was based on several national standards and terminology dictionaries of TCM,such as Zhong Yi Lin Chuang Zhen Liao Shu Yu Ji Bing Part and Zhong Yi Yao Xue Zhu Ti Ci Biao,supplemented with related corpus on the Internet,and the framework of TCM word network was constructed with ontology as the guide.Word2Vec was used to load pre-trained models for similarity calculation,statistical and rule-based new word discovery,bibliometric analysis,and other methods to add or delete concept words and synonyms such as symptom terms and prescription terms.Results The TCM word network contained 55 semantic types and 13 semantic relationships,more than 110 000 concept words,and more than 300 000 synonyms.In addition to classifying concept words by semantic types,more detailed semantic classification was carried out in the upper and lower tree structures,in which more than 30 000 concept words had superordinate words,and nearly 2 600 concept words had subordinate words.At the same time,a process-based terminology supplementation mechanism,update review mechanism and cleaning mechanism were created.Conclusion TCM word network can not only be applied to the natural language processing process of TCM-clinical decision support system,but also can be applied to the normalization of data and the automatic construction of knowledge graph.

Objective To investigate the risk factors influencing postoperative recurrence of abdominal wall endometriosis(AWE).Methods A retrospective analysis was conducted on clinical data of 225 AWE patients who underwent surgery between January 2015 and December 2021.The follow-up period ranged from 30 to 108 months(mean,62.2±23.3 months).There were 16 cases of recurrence and 209 cases of non-recurrence.Univariate analysis and multivariate logistic regression were performed to identify factors associated with postoperative recurrence.Results Univariate analysis revealed that prior AWE resection history,preoperative VAS score,intraoperative lesion number,maximum diameter,and postoperative medication were significantly correlated with recurrence(P＜0.05).Multivariate logistic regression identified three independent risk factors for recurrence:prior AWE resection history(OR=4.082,95％ CI:1.019-16.354,P=0.047),multiple intraoperative lesions(OR=5.275,95％ CI:1.560-17.834,P=0.007),and absence of postoperative pharmacotherapy(OR=6.256,95％ CI:1.479-26.457,P=0.013).Conclusion Patients with a history of prior AWE excision,multiple lesions,or lack of postoperative pharmacotherapy are at higher risk of recurrence of AWE.

Objective To conduct a clinical comprehensive evaluation of Lu Dangshen Oral Liquid from 6 dimensions,including safety,effectiveness,economic value,innovativeness,suitability and accessibility.Methods The clinical evidence of Lu Dangshen Oral Liquid and seven control drugs(Bufei Huoxue Capsules,Xiangsha Liujun Pills,Jinshuibao Capsules,Shenling Baizhu Granules,Yupingfeng Granules,Zhenqi Fuzheng Granules and Bailing Capsules)were obtained by using quantitative and qualitative methods through literature retrieval,questionnaire survey and data collection.Based on the multi criteria decision analysis(MCDA)model,the clinical value of drugs was comprehensively evaluated.The weights of criterion layer,index layer and alternative scheme were calculated by analytic hierarchy process.The equal frequency discretization rule was used to classify the evaluation results.Results The safety evidence showed that the main adverse reactions were epistaxis and nausea,and there were no serious adverse events.The comprehensive evaluation was grade A(the risk was controllable and the evidence was sufficient).Clinical studies showed that its treatment of lung spleen qi deficiency syndrome reflects the idea of treating different diseases with same method,and its efficacy in stable chronic obstructive pulmonary disease and children with recurrent respiratory tract infection was better than conventional treatment or Spleen Aminopeptide Oral Lyophilized Powder,and its effectiveness was rated as grade A.In terms of economy,the daily drug cost was relatively high,and it was rated as grade C.The preparation process was authorized by one patent.The single Chinese materia medica could improve the diseases and symptoms related to lung spleen qi deficiency syndrome,and the innovation was rated as grade A.In the questionnaire survey,the clinical use and patient compliance were excellent,and the suitability was rated as grade A.The supply of raw materials was stable,and the accessibility was rated as grade B.Conclusion The comprehensive evaluation of the clinical value of Lu Dangshen Oral Liquid in the treatment of lung spleen qi deficiency syndrome is grade A,which can provide references for the adjustment of the national medical insurance catalog and the national essential medicine catalog.

Objective:To explore the correlation between conventional ultrasound and contrast-enhanced ultrasound features and invasive histological features of T 1a clear cell renal cell carcinoma (ccRCC). Methods:A retrospective case series study was conducted. Sixty-seven T 1a ccRCC patients who were admitted to Shanxi Province Cancer Hospital from May 2018 to August 2023 were selected. According to the World Health Organization (WHO)/International Society of Urology and Pathology (ISUP) renal tumor grading system, the patients were divided into the low-grade group (WHO/ISUP grades 1-2, 53 cases) and the high-grade group (WHO/ISUP grades 3-4, 14 cases). The conventional ultrasound and contrast-enhanced ultrasound characteristics of two groups of patients were compared. Multivariate logistic regression model was used to analyze the independent factors of conventional ultrasound and contrast-enhanced ultrasound related to T 1a ccRCC with WHO/ISUP high grade. Results:There were no statistically significant differences in clinical characteristics between the two groups of patients (all P > 0.05). In conventional ultrasound examination, the proportion of patients with tumor exophytic rate <50% in the high-grade group was higher than that in the low-grade group [64.3% (9/14) vs. 34.0% (18/53)], and the difference was statistically significant ( χ2 = 4.23, P = 0.040); there were no statistically significant differences in the distribution of patients with different tumor maximum diameter, laterality, polarity, depth, echo, boundary, and shape between the two groups (all P > 0.05). In contrast-enhanced ultrasound examination, the proportion of patients lack of pseudocapsule sign in the high-grade group was higher than that in the low-grade group [57.1% (8/14) vs. 24.5% (13/53)], and the difference was statistically significant ( χ2 = 4.06, P = 0.044); there were no statistically significant differences in the distribution of patients with different perfusion mode, enhancement degree, enhancement uniformity, and regression mode between the two groups (all P > 0.05). Multivariate logistic regression analysis showed that the conventional ultrasound tumor exophytic rate < 50% (compared to exophytic rate ≥ 50%, OR = 3.732, 95% CI: 1.019-13.664, P = 0.047) and the absence of pseudocapsule sign (compared to the presence of pseudocapsule sign, OR = 4.357, 95% CI: 1.201-15.804, P = 0.025) on contrast-enhanced ultrasound were independent risk factors for high-grade T 1a ccRCC. Conclusions:T 1a ccRCC with the exophytic rate <50% and absence of pseudocapsule sign may have invasive histological features.