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.

Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.

ObjectiveTo study the traditional Chinese medicine （TCM） syndromes of children with alopecia areata， and provide evidence for TCM differentiation and treatment in clinic. MethodsA retrospective analysis was conducted on the clinical data of 800 children with alopecia areata admitted to the Hair Medicine Center of the China-Japan Friendship Hospital from January 1， 2012 to December 31， 2021. The clinical data of the children were collected using a four-examination information questionnaire， including clinical characteristics （age of consultation， age of onset， course of disease， family history， severity grading）， alopecia areata-related factors （triggers）， and four-examination information （including sleep， diet， emotions， bladder and bowel function， etc.）. Descriptive frequency analyses， rank sum tests， factor analyses and cluster analyses were performed， and the distribution of the major TCM syndromes was summarised with the clinical data. ResultsThere were 800 children with alopecia areata， including 449 males and 351 females； 8 cases （1.00%） were in infancy， 36 cases （4.50%） were in early childhood， 180 cases （22.50%） were in preschool， 380 cases （47.50%） were in school age， and 196 cases （24.50%） were in puberty at the time of consultation； the average age of consultation was 8.31±3.86 years， the average age of onset of disease was 5.40±3.82 years， and the average duration of disease was 2.94±2.77 years； 527 children （65.87%） with severe alopecia areata； 85 children （13.56%） had a family history of alopecia areata； 772 children （96.50%） had unknown triggers for their first alopecia areata， and 28 children （3.50%） reported the presence of obvious triggers， including fright （9 cases）， high fever （5 cases）， allergic reactions （4 cases）， micronutrient （zinc， iron， etc.） deficiencies （4 cases）， inappropriate diet （2 cases）， environmental factors （1 case， new house renovation）， atopic dermatitis （1 case）， atopic asthma （1 case）， and pneumonia （1 case）. A total of 40 four-examination information items were collected， among which the frequency of kicking quilts was the highest with 380 cases （47.50%）， followed by picky eating （369 cases， 46.13%）， sleeplessness （334 cases， 41.75%）， irritability （334 cases， 41.75%）， partiality towards certain foods （306 cases， 38.25%）， impulsiveness （297 cases， 37.13%）， dry stools （233 cases， 29.13%）， yellow urine （215 cases， 26.88%）， nail biting （213 cases， 26.63%）， bad breath （211 cases， 26.38%）. According to factor analysis and cluster analysis， five types of TCM syndromes were obtained， in order as qi and blood deficiency syndrome （110 cases， 13.75%）， spleen deficiency syndrome （114 cases， 14.25%）， kidney essence deficiency syndrome （140 cases， 17.50%）， dietary stagnation syndrome （150 cases， 18.75%）， and liver depression and spleen deficiency syndrome （286 cases， 35.75%）. Patients in each age group and SALT grading are mainly liver depression and spleen deficiency syndrome. ConclusionThe TCM symptoms of children with alopecia areata are mainly based on qi and blood deficiency syndrome， spleen deficiency syndrome， kidney essence deficiency syndrome， dietary stagnation syndrome， and liver depression and spleen deficiency syndrome， of which liver depression and spleen deficiency syndrome is the most common type at different ages and stages of the disease.

Objective This study aimed to investigate the therapeutic efficacy of Sanjie Quban recipe in a keloid nude mice model and its impact on transforming growth factor-β 1(TGF-β1).Methods Keloid tissue after surgical resection was subcutaneously transplanted into the backs of healthy SPF BALB/C female nude mice,aged 6～8 weeks,and a keloid nude mice model was thus established.The mice were randomly divided into three groups,the Sanjie Quban recipe group,the Asiaticoside tablet group and the control gnup,with five in each group.They were respectively treated with Sanjie Quban recipe,Asiaticoside tablets,or sterile pure water.After 28 days of continuous gavage,the keloid tissue was exfoliated and weighed,and HE staining,Masson staining,and immunohistochemical staining for TGF-β1 were conducted.Differences in keloid weight between the three groups before and after treatment were compared,as were the differences in collagen fiber,fibroblast numbers,and TGF-β1 expression between the three groups after treatment.Results The difference in keloid weight before and after treatment in the Asiaticoside tablet group was greater than that of the control group,and the weight difference before and after treatment keloid treatment was the largest in the Sanjie Quban recipe group(P＜0.01).Compared with the control group,collagen fibers in the Sanjie Quban recipe group were looser and less numerous,and fibroblasts were decreased in number.The expression of TGF-β1 in the Sanjie Quban recipe group was decreased compared with that of the control group(P＜0.01).Conclusions Sanjie Quban recipe has certain therapeutic effects on keloids.The mechanism may involve reducing the expression of TGF-βl in keloid tissue and thereby reducing the proliferation of fibroblasts and the synthesis of extracellular matrix.This study provides experimental and theoretical bases for the clinical treatment of keloids with Chinese medicine.

Objective To explore the effects of Shaoyao Gancao granule on hair growth,behavior,and the hypothalamic pituitary adrenal(HPA)axis in mice with alopecia areata(AA).Methods Forty-two C3H/HeJ mice were randomly divided into control,model,Shaoyao Gancao granule high-,middle-,low-dose,corticotropin-releasing hormone receptor 1(CRHR1)antagonist,and compound glycyrrhizin tablet(CGT)groups.Photography,dermoscopy,weight analysis,and behavioral measurement were performed.Corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),cortisol,glucocorticoid receptor(GR),and brain-derived neurotrophic factor(BDNF)were also assessed.Results Compared with the model group,high-dose Shaoyao Gancao granules improve hair regeneration and weight gain(P＜0.05),increased the percentage of total exercise distance and central area exercise distance in an open field test(P＜0.05),reduced the immobility time in the forced swimming and tail suspension experiments(P＜0.05),reduced peripheral blood levels of CRH,ACTH,and cortisol(P＜0.05),and increased expression of GR and BDNF in the hippocampus(P＜0.05).Conclusions Shaoyao Gancao granule promotes hair growth and improves behavioral performance in mice with AA.These effects may be related to downregulating CRH,ACTH,and cortisol expression,upregulating GR and BDNF expression,and inhibiting excessive activation of the HPA axis.

ObjectiveTo explore the distribution of traditional Chinese medicine （TCM） syndromes of alopecia areata （AA）， and to provide reference for TCM clinical syndrome differentiation and classification of AA. MethodsAA patients who visited the specialized hairiness clinic of Beijing China-Japan Friendship Hospital were included. A questionnaire was developed including general information of the patients， history of hair loss （onset time， triggers and exacerbating factors， disease progression）， current symptoms （symptoms and signs）， medical history， personal history， family history， and hair microscopy examination results. The factor analysis and cluster analysis were used to determine the syndrome elements and to summarize the syndrome types. ResultsA total of 600 patients with AA were included， including 218 males （36.33%） and 382 females （63.67%）. Totally， 128 patients （21.33%） had a family history of hair loss， and 326 patients （54.33%） had a previous related underlying disease. The leading triggering and exacerbating factors of AA were tension and anxiety， accounting for 335 cases （55.83%） and 285 cases （47.50%）， respectively. The top 10 symptoms involved among patients were scalp oil， anxiety， irritability， dreaminess， fatigue， itching， tension， weakness and dandruff. The factor analysis showed that the factor rotation converged after 9 iterations， and finally obtained 12 common factors and 34 variables， with a cumulative contribution rate of 58.59%. In terms of disease location of AA， the main syndrome elements were liver， spleen and kidney， and the disease nature syndrome elements were mainly dampness-heat， qi stagnation， yin deficiency， qi deficiency， and blood deficiency. The clustering analysis of the 12 common factors showed that TCM syndromes could be summarized into four categories： internal retention of damp-heat， liver-kidney deficiency， qi and blood deficiency， and liver constraint and spleen deficiency. There were significant differences in the distribution of TCM syndromes in patients of different ages and genders （P＜0.001）. ConclusionThe main disease location of AA is in the liver， spleen， and kidney， with the liver being the key. The disease mechanism of AA is a deficiency-excess complex， initially manifested as excess and later becoming deficiency. The TCM syndromes mainly include four types which are internal retention of damp-heat， liver-kidney deficiency， qi and blood deficiency， and liver constraint and spleen deficiency.

Objective:To detect the effect of pulse radiofrequency (PRF) treatment on the neuropathic pain established by L5-spinal nerve ligation (SNL) on rats,and to investigate if PRF treatment would affect the expression of autophagy related protein LC3 and autophagy related receptor P62 at the dorsal horn.Methods:A total of 36 male Sprague-Dawley rats were randomly divided into 3 groups:a Sham group,a SNL group,and a SNL+PRF group.The 50％ paw withdrawal mechanical threshold (PWMT) was detected at 1 day before and 1,3,7,14 and 28 days post-operation by using Von-Frey filaments.The autophagy related protein LC3 and autophagy related receptor P62 were investigated by Western blot.Results:Compared with the Sham group,the PWMT significantly decreased in the SNL group at each time points (P＜0.05);in SNL+PRF group,PRF treatment could elevate the PWMT at the 1st day post-operation and lasted for 28 days (P＜0.05).What's more,SNL could elevate the LC3-Ⅱ and P62 levels at the 7th day post-operation (P＜0.05),which were decreased by the PRF treatment (P＜0.05).Conclusion:PRF treatment could improve SNL-induced the neuropathic pain,which might be partly due to the regulatory effects on the autophagy levels at the spinal dorsal horn.

Objective To evaluate the effect of extensive resection and immediate reconstruction based on classification of abdominal wall defects for patients with abdominal wall neoplasms.Methods From Jan 1999 to May 2016,112 patients with abdominal wall neoplasms were treated with extensive resection,including Type Ⅰ (n =20),Type Ⅱ (n =45) and Type Ⅲ (n =47).Immediate abdominal wall reconstruction comprised primary sutures or free skin graft for Type I defects,component separation (CST) with or without a prosthetic or biological mesh reinforcement for Type Ⅱ defects and pedicled or vascularized myocutaneous flap with or without a prosthetic or biological mesh or prosthetic + biological mesh with or without CST for Type Ⅲ defects.Results The average follow up was 76.86 ± 21.22 months,3 patients developed flap necrosis,9 patients suffered from wound infection.Local recurrence was observed in 20 patients,35 patients developed distant metastasis.Conclusions The optimal strategy based on the abdominal wall defect classification for immediate reconstruction of huge abdominal wall defects is safe and effective after resection of abdominal wall neoplasms.

Objective To investigate the roles of phosphatidylinositol 3 kinase (PI3K) and phosphorylated Akt (P-Akt) in the pathogenesis of cervical squamous cell carcinoma and condyloma acuminatum.Methods Immunohistochemistry and Western blot were used to detect the expressions of PI3K and P-Akt in tissue specimens from the lesions of 30 cases of cervical squamous cell carcinoma,30 cases of condyloma acuminatum and the prepuce of 15 normal human controls.The average optical density and gray scale values were calculated and analyzed by t test and F test respectively.Results The expressions of PI3K and P-Akt were observed in only the basal layer of the epidermis of control specimens,but in the whole epidermis of condyloma acuminatum tissue specimens.Cervical squamous cell carcinoma tissue specimens displayed a stronger expression of PI3K and P-Akt compared with the control and condyloma acuminatum tissue specimens.As immunohistochemistry revealed,the average absorbance value for PI3K and P-Akt was 0.28 ±0.05 and 0.20 ± 0.07 respectively in cervical squamous cell carcinoma tissue specimens,0.22 ± 0.04 and 0.17 ± 0.03 respectively in condyloma acuminatum tissue specimens,and 0.16 ± 0.04 and 0.10 ± 0.02 respectively in the control tissue specimens; significant differences were observed in the expressions of PI3K and P-Akt among the three groups of tissue specimens (F =44.87,20.64,respectively,both P ＜ 0.01 ).The results of Western blot were consistent with those of immunohistochemistry,and there was a significant difference in the gray scale value for PI3K and P-Akt between cervical squamous cell carcinoma,condyloma acuminatum and control tissue specimens (3.48 ± 0.48 vs.1.99 ± 0.11 vs.1.00 ± 0.03,F=354.83,P＜ 0.01; 3.33 ± 0.26 vs.1.96 ± 0.11 vs.1.00 ± 0.03,F=302.33,P＜ 0.01 ).Conclusions The PI3K/Akt signaling pathway is abnormally activated in condyloma acuminatum and cervical squamous cell carcinoma,and human papilloma virus may cause the abnormal proliferation of infected epithelium likely by affecting the upregnlated expression of PI3K/P-Akt.