International registration of herbal drugs is a necessary prerequisite for the internationalization of Chinese materia medica. North America and European Union occupy an important position in the world herbal drugs market, and their drug administration and quality supervision requirements are relatively complete and progressiveness. By summarizing the definition of herbal drugs in North America and European Union, combing and interpreting the relevant laws, regulations and policy documents, this article constructed the registration path of herbal drugs, and discussed the current status of market registration of herbal drugs in North America and European Union based on the examples of successful marketing of herbal drugs under current application and approval in overseas markets. This article believed that in the future, an internationally matched TCM quality standard evidence system should be built, clinical trials of TCM products in line with international standards should be carried out, standards that are the same or higher than international mainstream GMP should be developed, the registration path of TCM compounds should be explored, and professionals to establish an international registration application team should be recruited to provide theoretical and practical support for China's overseas registration of Chinese TCM products, promote TCM products to enter the world mainstream market, and achieve high-quality development of TCM internationalization.

Objective:To explore the role of combined detection of cell free BMPR1A and PLAC8 gene methylation in plasma in predicting postoperative recurrence of hepatocellular carcinoma.Methods:Case series study. Patients with stage Ⅰ-Ⅳ hepatocellular carcinoma who were treated at the Third Affiliated Hospital of Sun-Yat-sen University from January 2022 to July 2023 were selected. All enrolled patients underwent alpha fetoprotein (AFP) and imaging assessments 1 month, 3 months, 6 months, 9 months, and 12 months after treatment. Simultaneously, peripheral blood of patients was extracted for plasma circulating tumor DNA (ctDNA) methylation detection, and the results of free BMPR1A and PLAC8 gene methylation detection in patients′ plasma after treatment were compared with the positive rate of traditional tumor marker AFP detection. Draw the receiver operating characteristic curve (ROC) of the subjects to demonstrate the effectiveness of this method in predicting the recurrence of hepatocellular carcinoma. Based on the results of cell free DNA methylation and whether AFP is more than 7 μg/L, hepatocellular carcinoma patients were divided into high-risk methylation group (12 cases), low-risk methylation group (21 cases), high-risk AFP group (15 cases), and Kaplan Meier survival analysis was performed on them.Results:The sensitivity and specificity of combined detection of free BMPR1A PLAC8 gene methylation in plasma for predicting liver cancer recurrence were 66.7% and 88.9%, respectively. The area under curve (AUC) of BMPR1A PLAC8 gene methylation detection for liver cancer recurrence were 0.770 and 0.778, and the AFP was 0.522 in ROC curve analysis. Compared to imaging examinations, cell free DNA methylation detection can detect the recurrence of hepatocellular carcinoma on average by 58.3 days in advance(53.8 days vs 112.1 days). The progression free survival rate of the high-risk group based on free DNA methylation prediction at 400 days was 22.2%, significantly lower than the low-risk group (76.2%, P<0.001). Conclusion:Compared to AFP, detecting the methylation of BMPR1A and PLAC8 genes can predict the recurrence of hepatocellular carcinoma more accurately, making it a practical method for monitoring liver cancer recurrence.

BackgroundCombination of antipsychotic drugs and modified electroconvulsive therapy （MECT） is currently a commonly used method for treating schizophrenia， but its efficacy varies among different patient groups. ObjectiveTo explore the therapeutic effects of MECT on schizophrenia patients living in different urban versus rural environments， so as to provide references for the selection of treatment plans based on patients' residence. MethodsA total of 587 patients hospitalized at Luzhou Mental Health Center， Zigong Mental Health Center and Yibin Fourth People's Hospital from May 2018 to August 2022， who met the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） ，were included in the study. Patients were divided into two groups： medication-only group （n=106） and MECT combined with medication group （n=481）. In MECT combined with medication group， 24 rural patients residing in urban areas were excluded， leaving the remaining patients divided into urban group （n=103） and rural group （n=354） based on their place of residence. Positive and Negative Syndrome Scale （PANSS） was used to assess the severity of symptoms. Clinical efficacy was evaluated using PANSS score reduction rate， and covariance analysis was used to compare the therapeutic effects of different patients. ResultsThe differences of reduction rate of PANSS total score， positive symptom scale score and negative symptom scale score as well as treatment effectiveness rate between MECT combined with medication group and medication-only group were statistically significant （F=11.149， 12.111， 31.725， χ²=14.010， P<0.01）. Statistically significant differences were also observed in reduction rate of PANSS total score and positive symptom subscale score as well as treatment effectiveness rate between urban and rural patients in MECT combined with medication group （F=3.946， 4.523， χ²=4.033， P<0.05）. ConclusionThe efficacy of MECT combined with medication may be superior to medication alone in the treatment of schizophrenia， and the combined therapy may be more effective in urban patients than that in rural patients， with potentially more pronounced improvements in positive symptoms.

Objective This study aimed to explore the differences and influencing factors of static teeth exposure in different postures of orthognathic surgery patients.Methods A total of 148 patients were collected before or after or-thognathic surgery.Photographs were taken in the upright and supine positions,and the static teeth exposure values were measured to compare whether the difference among different positions was statistically significant.The patients were classified in accordance with gender,presence or absence of orthodontic brackets,measurement time(preoperative or postoperative),and maxillary movement direction(forward or backward),and the difference of static teeth exposure was compared.The correlation between the difference of static teeth exposure and age was analyzed.Results The diffe-rence of static teeth exposure between the two positions was 0.99 mm±0.95 mm,which was statistically significant(P=0.000).A statistical difference in the difference of static exposure was observed between female and male(P<0.05).No statistical difference in the difference of static expo-sure was observed among orthodontic brackets,preopera-tive or postoperative time points,and maxillary move-ment direction.In addition,no significant correlation was found between the difference of static teeth exposure and age(r=-0.087,P=0.291).Conclusion Compared with the upright position,the static exposure of teeth increased by ap-proximately 0.99 mm in the supine position.The difference of static exposure under different postures was greater in males than in females.Furthermore,orthodontic bracket,maxillary surgery,maxillary movement direction,and age had no effect on the difference of static teeth exposure in different postures.

Objective To investigate the clinical characteristics of female migraine patients with patent foramen ovale(PFO)and design a risk prediction model for PFO in female migraine patients(migraineur patients PFO risk prediction model,MPRPM).Methods Female migraine patients who visited Zhongshan Hospital,Fudan University from Jun 1,2019 to Dec 31,2022 were included.Preoperative information and follow-up results after discontinuation of medication were collected.Patients were divided into PFO-positive and PFO-negative groups based on transesophageal echocardiography results.A multivariate Logistic regression model and a random forest model were constructed,and the random forest model was validated multidimensionally.Key features were selected based on the mean decrease accuracy(MDA)to construct MPRPM.Results A total of 305 female patients were included in the study,with 204 patients in the PFO-positive group and 101 patients in the PFO-negative group.Multivariate Logistic regression analysis showed that age at migraine onset,attack frequency,severe impact on life during attacks,exercise-related headaches,menstruation-induced headaches,aura migraines,and a history of cryptogenic stroke were predictive factors for PFO positivity.The random forest model effectively predicted the incidence of PFO in female migraine patients,with an AUC of 0.895(95%CI:0.847-0.943).MPRPM demonstrated a sensitivity of 71.6%and specificity of 91.1%(AUC:0.862,95%CI:0.818-0.906,P<0.001).The optimal cut-off value was 2.5 points.Patients correctly classified by the model showed a higher rate of symptom improvement compared to incorrectly classified patients(94.3%vs.82.0%,P=0.023).Conclusion We identified predictive factors for PFO in migraine patients.MPRPM can provide guidance in the diagnostic process and therapeutic decision-making for female migraine patients,assist in patient triage,and reduce the healthcare burden.

Objective To explore the ideas,methods and pathways for the registration of Chinese medicine prescriptions in overseas countries,to form a strategy for overseas registration of Chinese medicine,and to provide technical support and reference for China's Chinese medicine prescriptions to go abroad.Methods Five representative countries were selected to form corresponding expert teams and exchange platforms for international cooperation.The laws,regulations,rules,standards,specifications and technical guidance documents related to Chinese medicine prescription preparations of the target countries were used as pathway research materials,and the documents were translated directly,naturalized,proofread and diagrammed,and a problem-oriented mechanism for consultation with domestic and international experts was established to form a pathway for overseas registration of Chinese medicine prescription preparations.Results The path for standardization of overseas registration of Chinese medicines was clarified,and the detailed registration paths and corresponding work strategies of Chinese medicines in five countries were formulated with flow charts,tables and explanatory texts.Conclusion By developing standardized registration pathways for traditional Chinese medicine in target countries,reference can be provided for the internationalization of Chinese herbal formula preparations.

Objective To investigate the effects of the physical parameters of radiotherapy and intestinal flora on the risk of secondary radiation enteritis(RE)in patients with abdominal malignant tumors.Methods Ninety-eight patients with malignant abdominal tumors who were treated with radiotherapy from April 2020 to August 2023 at Anyang District Hospital in Puyang City were selected and assigned to the RE group(n=26)or the non-RE group(n=72).The clinical data,physical parameters of radiotherapy,and changes in the intes-tinal flora were compared between the two groups.Pearson's correlation analysis was used to determine the correlation between the phy-sical parameters of radiotherapy and changes in the intestinal flora,and logistic analysis was used to analyze the relationship between the physical parameters of radiotherapy,changes in the intestinal flora,and risk of RE.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to analyze the physical parameters of radiotherapy and changes in intestinal flora in predicting risk of RE.Results The doses of V20,V40,and D2cc in the small intestine,D2cc in the rectum,and D2cc in the colon were higher in the RE group than in the non-RE group(P＜0.05).The α diversity Chao1 index,Shannon index,and Simpson index of the intestinal flora in the RE group were lower than in the non-RE group,at the third week of radiotherapy,and the decrease in the α diversity Chao1 index,Shannon index,and Simpson index of the intestinal flora in the RE group was greater than in the non-RE group,before and after radiotherapy(P＜0.05).The doses of V20,V40,and D2cc in the small intestine,D2cc in the rectum,and D2cc in the colon were posi-tively correlated with decreases in the α diversity Chao 1 index,Shannon index,and Simpson index of the intestinal flora,before and after radiotherapy(P＜0.05).The logistic analysis showed that the decrease in V20,V40,and D2cc in the small intestine,D2cc in the rectum,D2cc in the colon,α diversity Chao1 index,Shannon index,and Simpson index of the intestinal flora were independent risk factors for occurrence of RE(P＜0.05).The AUC of the physical parameters of radiotherapy and changes in intestinal flora combined to predict the risk of RE as 0.920,which was greater than that of each indicator alone.Conclusion The physical parameters of radiotherapy are closely related to the changes of intestinal flora in patients with malignant abdominal tumors,which,in combination,can increase the risk of RE,and have a high predictive value for the risk of RE.

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 establish a mesenchymal stem cell(MSC)-based in vitro cell model for the evaluation of mouse bone marrow acute graft-versus-host disease(aGVHD).Methods:Female C57BL/6N mice aged 6-8 weeks were used as bone marrow and lymphocyte donors,and female BALB/c mice aged 6-8 weeks were used as aGVHD recipients.The recipient mouse received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1× 107/mouse)in 6-8 hours post irradiation to establish a bone marrow transplantation(BMT)mouse model(n=20).In addition,the recipient mice received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1 × 107/mouse)and spleen lymphocytes(2 × 106/mouse)in 6-8 hours post irradiation to establish a mouse aGVHD model(n=20).On the day 7 after modeling,the recipient mice were anesthetized and the blood was harvested post eyeball enucleation.The serum was collected by centrifugation.Mouse MSCs were isolated and cultured with the addition of 2％,5％,and 10％recipient serum from BMT group or aGVHD group respectively.The colony-forming unit-fibroblast(CFU-F)experiment was performed to evaluate the potential effects of serums on the self-renewal ability of MSC.The expression of CD29 and CD105 of MSC was evaluated by immunofluorescence staining.In addition,the expression of self-renewal-related genes including Oct-4,Sox-2,and Nanog in MSC was detected by real-time fluorescence quantitative PCR(RT-qPCR).Results:We successfully established an in vitro cell model that could mimic the bone marrow microenvironment damage of the mouse with aGVHD.CFU-F assay showed that,on day 7 after the culture,compared with the BMT group,MSC colony formation ability of aGVHD serum concentrations groups of 2％and 5％was significantly reduced(P＜0.05);after the culture,at day 14,compared with the BMT group,MSC colony formation ability in different aGVHD serum concentration was significantly reduced(P＜0.05).The immunofluorescence staining showed that,compared with the BMT group,the proportion of MSC surface molecules CD29+and CD 105+cells was significantly dereased in the aGVHD serum concentration group(P＜0.05),the most significant difference was at a serum concentration of 10％(P＜0.001,P＜0.01).The results of RT-qPCR detection showed that the expression of the MSC self-renewal-related genes Oct-4,Sox-2,and Nanog was decreased,the most significant difference was observed at an aGVHD serum concentration of 10％(P＜0.01,P＜0.001,P＜0.001).Conclusion:By co-culturing different concentrations of mouse aGVHD serum and mouse MSC,we found that the addition of mouse aGVHD serum at different concentrations impaired the MSC self-renewal ability,which providing a new tool for the field of aGVHD bone marrow microenvironment damage.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.