Taking the Ligustrum lucidum extract as an example, this study investigated the influence of external mechanical forces under different processing conditions on the crystallographic solid form and the key parameter of drug dissolution rate, so as to provide guidance for the preparation and quality control of traditional Chinese medicine preparations. Under different pulverization and tableting conditions, the change of crystallographic solid form of L. lucidum extract was observed by polarizing light microscope. Meanwhile, the effect of this change on the dissolution rate was investigated, and the mathematical relationship between crystal content and dissolution rate was analyzed. The results showed that the process of ball milling and tableting had a significant impact on the crystallographic solid form of L. lucidum extract. The amorphous extract displayed crystal transformation, which induced a significant decline in dissolution rate. Further studies revealed that there was a negative linear relationship between crystal content and dissolution rate. The results of this study indicated that the crystallographic solid form transformation of traditional Chinese medicine extracts might occur during the preparation process, which may cause potential risks to the quality of traditional Chinese medicine preparations. It is suggested that we should pay attention to and strengthen the investigation of the crystallographic solid form during the preparation process, so as to guarantee the safety, effectiveness, and quality controllability of traditional Chinese medicine preparations.

Objective:To investigate the relationship and clinical significance of circulating tu-mor DNA(ctDNA)methylation with postoperative recurrence of thyroid cancer.Method:5 pa-tients with recurrent thyroid cancer in our hospital from March 2021 to April 2022 were selected as the observation group,and 2 healthy volunteers were selected as the control group.The level of ctDNA methylation in peripheral blood of the two groups was detected by Illumina high-throughput sequencing system.Gene ontology(GO)function analysis and Kyoto gene and genome encyclope-dia(KEGG)signal pathway analysis were carried out on the methylation region genes with signifi-cant differences through the DAVID gene function analysis platform.Result:There were 7787 dif-ferential ctDNA methylation sites between the two groups.2914(37.4％)were hypermethylation sites and 4873(62.6％)were low methylation sites.GO functional analysis showed that differentially methylated genes were enriched in molecular functions such as DNA-binding transcriptional acti-vation,cell-substrate adhesion,glycoprotein complex and other cellular components.KEGG path-way analysis showed that differentially methylated genes were enriched in thyroid carcinoma signal pathway,cell adhesion molecules,RAP1 signal pathway,RAS signal pathway,MAPK signal path-way and so on.Conclusion:ctDNA methylation may be involved in cancer recurrence in postop-erative patients with thyroid cancer.Monitoring the level of ctDNA methylation in peripheral blood may be an effective method to indicate the recurrence or metastasis of thyroid cancer and guide clinical diagnosis and treatment.

Objective To explore the treatment for endometriosis(EMs)by Professor SITU Yi,a Guangdong famous traditional Chinese medicine physician,thus to provide reference for the diagnosis and treatment of EMs in traditional Chinese medicine based on personalized knowledge graph analysis and data mining technology.Methods Based on the literature research achievements of diagnosis and treatment of EMs,the ontology knowledge tree of famous physician's principles,methods,prescriptions and medicines was established by user-computer integration method.The medical records of EMs patients treated by Professor SITU Yi in the outpatient department of Guangdong Provincial Hospital of Chinese Medicine from 2013 to 2019 were collected.After standardization of the data of medical records,the knowledge set was defined,the knowledge map of TCM diagnosis and treatment of EMs was constructed,and the symptom characteristics and medication rules for EMs were analyzed.Results The core symptoms of EMs patients were dysmenorrhea,chronic pelvic pain and infertility,with the predominated syndrome of blood stasis.The pathogenesis of EMs patients was mainly due to qi stagnation,kidney deficiency,and qi deficiency.Frequent itemset analysis yielded the core drug groups of"Corydalis Rhizoma,Cyperi Rhizoma,Paeoniae Radix Alba""Lycii Fructus,Taxilli Herba,Poria,Dioscoreae Rhizoma"and"Aurantii Fructus,Leonuri Herba".The EMs word cloud map constructed on the basis of knowledge element clustering and neural network algorithm showed that the drug combinations of"Salviae Miltiorrhizae Radix et Rhizoma,Paeoniae Radix Rubra""Corydalis Rhizoma,Curcumae Radix""Cinnamomi Ramulus,Moutan Cortex,Paeoniae Radix Rubra,Poria""Salviae Miltiorrhizae Radix et Rhizoma,Paeoniae Radix Rubra,Sparganii Rhizoma,Curcumae Rhizoma""Chuanxiong Rhizoma,Corydalis Rhizoma"and"Taxilli Herba,Cuscutae Semen"were commonly used for the treatment of EMs by Professor SITU Yi.The results of hierarchical clustering analysis and association network construction for Chinese medicinals,symptoms and syndromes showed that there were complex inner link among the syndromes,symptoms and medication.Conclusion For the treatment of EMs,Professor SITU Yi usually adopt the methods of activating blood to remove stasis and tonifying kidney,and also performs the periodic therapy and simultaneous application of purging and nourishing therapeutics.Knowledge graph analysis and data mining based on semantic web are helpful to unveil the tacit knowledge of clinical diagnosis and treatment experience of Professor SITU Yi,which can provide reference for the differentiation and treatment of EMs with Chinese medicine.

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.

In order to guarantee the quality of traditional Chinese medicines (TCMs), the crystallization transformation of complex extracts of TCMs and the influence of solid form on their physicochemical properties were studied.The extract of total flavonoids from Pueraria lobata was taken as a model.Crystallization transformation happened when lofting under different conditions, and the intrinsic dissolution tests were carried out.It was found that humidity was the key factor to induce crystallization of total flavonoids from Pueraria lobata.The greater the wettability was, the more the crystallization was.The dissolution rate of total flavonoids from Pueraria lobata with the most crystallization amount significantly decreased by 96.51% compared to the sample without crystallization.After further simulating the preparation process of total flavonoids from Pueraria lobata, it was found that the wet granulation process with introduced water would also lead to crystallization and reduced dissolution rate.As for all crystallization samples, there was an inversely proportional relationship between the dissolution rates and the amount of crystallization.The risk of crystallization existed both in the storage and preparation process of TCM extracts.Crystallization would significantly affect the dissolution rate, and thus the quality of TCM products.In this study, the crystallization transformation of amorphous complex TCM extracts was discovered, and the effect of the crystallization transformation on its dissolution behavior was systematically studied, which provides a new research idea for assuring the quality of TCM products and promoting the improvement of TCM preparation level.

OBJECTIVE: To explore the effect of a modified three-point bending fracture device for establishing a rabbit model of closed tibial fracture. METHODS: The model of closed tibial fracture was established in 40 6-month-old male New Zealand white rabbits with a body weight of 2.5 to 3.0 kg, and the model was verified at 6 weeks after operation. Five rabbits underwent pre modeling without temporary external fixation before modeling, and then were fractured with a modified three-point bending fracture device;35 rabbits underwent formal modeling. Before modeling, needles were inserted, and splints were fixed externally, and then the fracture was performed with a modified three-point bending fracture device. The fracture model and healing process were evaluated by imaging and histopathology at 2 hours, 4 weeks, and 6 weeks after operation. RESULTS: Two hours after modeling, the prefabricated module showed oblique fracture in varying degrees and the broken end shifted significantly;Except for 1 comminuted fracture, 2 curved butterfly fractures and 2 without obvious fracture line, the rest were simple transverse and oblique fractures without obvious displacement in formal modeling group. According to the judgment criteria, the success rate of the model was 85.71%. Four weeks after modeling, the fixed needle and splint of the experimental rabbits were in good position, the fracture alignment was good, the fracture line was blurred, many continuous callus growths could be seen around the fracture end, and the callus density was high. Six weeks after modeling, many thick new bone trabeculae at the fracture, marginal osteoblasts attached, and a small number of macrophages were seen under the microscope. The intramembrane osteogenesis area was in the preparation bone stage, the medullary cavity at the fracture had been partially reopened, the callus was in the absorption plastic stage, and many osteoclasts were visible. The X-ray showed that the fracture line almost disappeared, part of the medullary cavity had been opened, the external callus was reduced around, the callus was in the plastic stage, and the bone cortex was continuous. It suggests that the fracture model showed secondary healing. CONCLUSION The improved three-point bending fracture device can establish a stable rabbit model of closed tibial fracture, and the operation is simple, which meets the requirements of closed fracture model in basic research related to fracture healing.
Rabbits ; Male ; Animals ; Bony Callus ; Fracture Healing ; Tibial Fractures/surgery* ; Osteogenesis ; Radiography

Objective: To establish a method for the determination of butyronitrile and isobutyronitrile in the air of workplace by gas chromatography. Methods: In March 2020, butyronitrile and isobutyronitrile in the air of workplace was collected by silica gel, eluted with methanol, separated and determined by gas chromatogram with flame ionization detector, the characteristics of determination of nitrile and isobutyronitrile by gas chromatography were analyzed. Results: The limit of detection for butyronitrile and isobutyronitrile was 0.33 μg/ml. The linear range of butyronitrile determined by this method was 1.60-1600.00 μg/ml, y=2.295x-3.480, and the coefficient correlation was 0.99998, and the minimum detection concentration was 0.22 mg/m(3) (collected sample volume was 1.50 L) . The within-run precisions were 2.43%-4.12%, the between-run precisions were 1.72%-3.70%, and the desorption rates were 93.26%-98.41%. The linear range of isobutyronitrile determined by this method was 1.52-1520.00 μg/ml, y=2.208x-0.102, and the coefficient correlation was 0.99998, and the minimum detection concentration was 0.22 mg/m(3) (collected sample volume was 1.50 L) . The within-run precisions were 2.52%-3.22%, the between-run precisions were 1.20%-3.82%, and the desorption rates were 96.85%-102.50%. The sealed samples could be stored at least 10 days at room temperature without significant loss. Conclusion: The method has the advantages of good precision, high sensitivity and simple operation. It is suitable for the simultaneous determination of butyronitrile and isobutyronitrile in the air of workplace.
Air Pollutants, Occupational/analysis* ; Chromatography, Gas/methods* ; Nitriles ; Workplace

OBJECTIVE: To compare the clinical efficacy between Wei's triple nine needling combined with esculin and digitalis glycosides eye drops and esculin and digitalis glycosides eye drops alone for presbyopia complicated with visual fatigue of liver depression and spleen deficiency. METHODS: Forty-six cases (92 eyes) with presbyopia complicated with visual fatigue of liver depression and spleen deficiency were randomly divided into an observation group (23 cases) and a control group (23 cases, 2 cases dropped off). The cases in the observation group were treated with Wei's triple nine needling and esculin and digitalis glycosides eye drops. The acupoints included Shangming (Extra), Chengqi (ST 1), Cuanzhu (BL 2) to Jingming (BL 1), Sizhukong (TE 23) to Taiyang (EX-HN 5), etc; the needling was given once every other day, three times a week, and the eye drops were given one drop each time, three times a day. The cases in the control group were only treated with the eye drops. Both groups were treated for 7 days as one course of treatment, and 2 courses of treatment were given. The visual fatigue core symptoms score, adjustment amplitude, adjustment lag and best average corrected visual acuity were observed in the two groups before treatment, 1 week and 2 weeks into treatment, respectively. RESULTS: Compared before treatment, the visual fatigue core symptoms scores in the two groups were decreased after 1-week and 2-week treatment (P<0.05); in the observation group, the adjustment amplitude was increased after 2-week treatment (P<0.05), while in the control group, the adjustment amplitude was increased after 1-week and 2-week treatment (P<0.05); in the observation group, the adjustment lag was decreased after 1-week and 2-week treatment (P<0.05). After 2-week treatment, the visual fatigue core symptoms score in the observation group was lower than that in the control group, and the adjustment amplitude was higher than that in the control group (P<0.05). There were no significant differences in adjustment lag and best average corrected visual acuity between the two groups after 1-week and 2-week treatment (P>0.05). CONCLUSION Wei's triple nine needling combined with esculin and digitalis glycosides eye drops could improve the visual fatigue and eye regulation ability in patients with presbyopia complicated with visual fatigue of liver depression and spleen deficiency, and the effect is better than esculin and digitalis glycosides eye drops alone.
Acupuncture Points ; Acupuncture Therapy ; Asthenopia ; Depression ; Digitalis Glycosides ; Esculin ; Humans ; Liver ; Ophthalmic Solutions ; Presbyopia ; Spleen ; Treatment Outcome

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Hepatotoxicity is a common side effect for patients treated with gefitinib, but the related pathogenesis is unclear and lacks effective predictor and management strategies. A multi-omics approach integrating pharmacometabolomics, pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution. Here, we found that patients with rs4946935 AA, located in Forkhead Box O3 (FOXO3) which is a well-known autophagic regulator, had a higher risk of hepatotoxicity than those with the GA or GG variant (OR = 18.020, 95%CI = 2.473 to 459.1784, P = 0.018) in a gefitinib-concentration dependent pattern. Furthermore, functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity, increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury. In contrast, erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3. This study reveals that FOXO3 mutation, leading to autophagic imbalance, plays important role in gefitinib-induced hepatotoxicity, especially for patients with high concentration of gefitinib. In conclusion, FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.