Yigongsan is derived from Xiaoer Yaozheng Zhijue written by QIAN Yi in the Northern Song dynasty， which is the No. 3 formula in the Catalogue of Ancient Famous Classical Formulas（The Second Batch of Pediatrics） released by the National Administration of Traditional Chinese Medicine（TCM） in September 2022， and it can be developed as a class 3.1 new TCM drug. By referring to ancient medical books and modern literature， this study conducted herbal textual research on Yigongsan from five aspects， including historical evolution， origin and processing， dosage conversion， usage and preparation methods， and functional application， then formed the key information table of this formula， in order to provide reference for the development of reference samples and preparations of Yigongsan. Based on the results of the study， it is recommended that Panax ginseng should be removed the basal part of stem（rhizoma）， Poria cocos should be removed the peel， Citrus reticulata should be cut into shreds and Glycyrrhiza uralensis should be used. According to 4.13 g/Qian（钱）， 1 g/slice for ginger， 3 g for each jujube and 300 mL/Zhan（盏）， the doses of Ginseng Radix， Poria， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma， Citri Reticulatae Pericarpium， Zingiberis Rhizoma Recens， Jujubae Fructus were 1.652， 1.652， 1.652， 1.652， 1.652， 5， 6 g， and the total amount was 19.26 g. The decocting method was to crush the medicinal materials into fine powder with 50-80 mesh， add 300 mL of water and decoct to 210 mL for each dose， then remove the dregs and take it warmly. This formula was recorded in ancient books as the main treatment for the cold-deficiency of spleen and stomach， and Qi stagnation in children with vomiting and diarrhea and lack of appetite. It has been flexibly applied by later generations of physicians， and is often used to treat anorexia， inflammation of the digestive tract， diarrhea and other diseases in children.

Background and purpose:The standard therapy for locally advanced rectal cancer(LARC)is neoadjuvant chemoradiotherapy(nCRT)followed by surgery.NCRT can make the tumor regress and downstage,and increase the R0 resection rate.However,individual differences in rectal cancer are large,and some patients respond poorly to nCRT and cannot benefit from nCRT.Therefore,it is necessary to establish effective screening measures to identify patients with poor response to nCRT.This study aimed to analyze the influencing factors of nCRT for LARC and construct the tumor regression prediction model.Methods:Data of 158 LARC patients who underwent total mesenteric resection after receiving nCRT at the First Hospital Affiliated to Air Force Medical University from January 2016 to December 2020 were collected.Baseline clinical indicators before nCRT were collected,including laboratory examination,tumor markers and magnetic resonance imaging(MRI).According to the tumor size reported by MRI before and after nCRT,Response Evaluation Criteria in Solid Tumors(RECIST)was used to evaluate the extent of tumor regression after nCRT.After receiver operating characteristic(ROC)curve was used to standardize the clinical baseline indicators,logistic regression analysis was carried out to screen the factors affecting the tumor regression.The tumor regression prediction model was constructed by logistic regression,and the performance of the model was evaluated based on decision curve analysis(DCA)and the calibration curve.The accuracy of the model was tested by 10-fold cross-validation.Results:This retrospective cohort study enrolled 158 patients,in which,98 patients achieved complete response(CR)or partial response(PR).The objective response rate was 62%.Sixty patients had poor response to nCRT,either stable disease(SD)or progressive disease(PD).Multivariate logistic regression analysis showed that tumor diameter before treatment(P＜0.001),time to surgery after nCRT(P = 0.006),D-dimer(P = 0.010),prognostic nutrition index(PNI)(P = 0.035),carcinoembryonic antigen(CEA)(P = 0.004)and extramural vascular invasion(EMVI)(P = 0.026)were significantly related to tumor regression after nCRT.The area under ROC curve(AUC)of tumor regression after nCRT prediction model for LARC was 0.84(95%CI:0.780-0.899),sensitivity was 85.0%,and specificity was 72.4%.In the calibration curve,the predicted results were in good agreement with the actual results,and the prediction accuracy was good.The DCA showed that the tumor regression prediction model could bring clinical net benefit to diagnosis.Conclusion:Tumor diameter before treatment,time to surgery after nCRT,D-dimer,PNI,CEA and EMVI are independent risk factors for the tumor regression after nCRT in LARC patients.The tumor regression prediction model based on the above factors has good predictive efficacy for the tumor regression after nCRT in LARC patients.

BACKGROUND:Intervertebral disk degeneration is a pathological change caused by a series of complex molecular mechanisms that result in the aging and damage of intervertebral discs,ultimately leading to severe clinical symptoms.Traditional Chinese medicine has unique advantages in the treatment of intervertebral disk degeneration due to its low cost,non-addictive nature,multi-target effects,minimally toxic and side effects,and high patient acceptance. OBJECTIVE:To review the latest research results of traditional Chinese medicine monomer intervention-related signaling pathways in the treatment of intervertebral disk degeneration,describe and analyze the action mechanism of traditional Chinese medicine monomer on intervertebral disk degeneration,and provide a new approach and theoretical basis for future basic research and clinical treatment. METHODS:The first author searched for relevant literature from January 2018 to February 2023 in CNKI,PubMed,VIP,and WanFang using the search terms"intervertebral disc,signal pathway".The articles that did not meet the criteria were excluded after preliminary screening of the titles and abstracts.Finally,72 articles were selected for review and analysis. RESULTS AND CONCLUSION:Traditional Chinese medicine monomers can regulate multiple classical signaling pathways such as Wnt/β-catenin,PI3K/Akt,mTOR,NF-κB,and MAPK.They achieve this by regulating oxidative stress,adjusting the expression of pro/anti-apoptotic proteins in cells,stimulating cellular autophagy function,reducing stimulation of cell inflammatory factors,increasing the expression of extracellular matrix markers,reducing the production of matrix-degrading enzymes,maintaining the synthesis and stability of extracellular matrix,inducing differentiation of mesenchymal stem cells in the nucleus pulposus into nucleus pulposus cells,promoting endogenous repair and reconstruction,controlling apoptosis and aging of nucleus pulposus cells,and increasing the activity of nucleus pulposus cells.These actions improve the microenvironment within the intervertebral disc,maintain the normal physiological function of the intervertebral disc,and delay intervertebral disc degeneration.

ObjectiveTo establish the fingerprint of seven commercially available Yangyin Qingfei preparations， to quantitatively analyze the index components， to evaluate their quality uniformity with multivariate statistical analysis， and to explore the quality differences among different dosage forms. MethodA total of 33 batches of commercially available 7 kinds of Yangyin Qingfei preparations were analyzed by high performance liquid chromatography（HPLC）， the fingerprints were established and the common peaks were identified. Paeoniflorin， verbascoside， harpagoside， glycyrrhizic acid and paeonol were selected as the indicators of quality attributes to quantitatively analyze 33 batches of preparations. Based on the administration methods of Yangyin Qingfei preparations， the daily intake was calculated and the radar charts were poltted， and cluster analysis and principal component analysis were used to explore the quality differences of 7 kinds of Yangyin Qingfei preparations and the quality uniformity among different batches of the same dosage form. ResultThe similarity of fingerprints of 7 dosage forms was 0.248-0.956， suggesting that there were significant differences among different dosage forms of Yangyin Qingfei preparations， and a total of 15 common peaks were calibrated， of which peak 7， peak 8， peak 11， peak 13 and peak 15 were paeoniflorin， verbascoside， harpagoside， glycyrrhizic acid and paeonol， respectively. The radar plots showed that the average total daily intake of large honeyed pills and water honeyed pills was the highest， and the uniformity of pill components was better. The quality of 33 batches of samples was divided into poor quality and high quality by cluster analysis. Principal component analysis showed that the uniformity and dosage form of different dosage forms were significantly different， the oral liquid had the best quality homogeneity with the minimum dispersion. And the content of paeonol in different dosage forms was significantly different， which was the key component of quality control of Yangyin Qingfei preparations. ConclusionYangyin Qingfei large honeyed pills and water honeyed pills show high content and good uniformity， which are relatively preferred dosage forms. Different preparation processes have a great influence on the content of paeonol， and its quality control should be emphasized during production. This study provides a scientific method for the comparison of product quality of different dosage forms of traditional Chinese medicine prescriptions， which is helpful for the development of preferred dosage forms of different prescriptions， and provides a reference for efficient use of medication in the clinical practice.

ObjectiveTo explore the pretreatment methods to promote the enzymatic digestion and extraction of active ingredients from Magnoliae Officinalis Cortex dregs（MOCD）， and to provide a reference basis for the utilization of resource components in MOCD. MethodLiquid chromatography-mass spectrometry（LC-MS） was used for qualitative analysis of resource components in MOCD with an Agilent C₁₈ reversed-phase column（3.0 mm×100 mm， 2.7 µm） at the flow rate of 0.4 mL·min^-1， the mobile phase was water（A）-acetonitrile（B） for gradient elution（0-3 min， 25%-48%B； 3-6 min， 48%-59%B； 6-10 min， 59%-80%B； 10-20 min， 80%-90%B； 20-25 min， 90%B）， electrospray ionization（ESI） was employed with negative ion mode scanning and scanning range of m/z 50-1 200. A high performance liquid chromatography（HPLC）， which refered to the determination in the 2020 edition of Chinese Pharmacopoeia， was used for quantitative analysis of resource components in MOCD. Four kinds of pretreatment agents were used to separate the resource components from MOCD， and the mechanism of different pretreatment agents was investigated by field emission scanning electron microscopy（FESEM）， X-ray powder diffraction（XRD） and Fourier transform infrared spectroscopy（FT-IR）. ResultMagnolol， honokiol and lignocellulose were identified as the main resource components of MOCD by qualitative and quantitative analysis. Under the conditions of 1% NaOH， reaction temperature at 80 ℃ and reaction time of 60 min， the concentration of reducing sugar produced by the enzymatic hydrolysis was 32.18 g·L^-1， which was 79.8% higher than that of the untreated MOCD. After adding tween-80， the enzymatic hydrolysis time was reduced to 1/3 of the original time， the concentration of reducing sugar was increased by 102.0%. And the total recovery of magnolol and honokiol in the pretreatment solution was 69.23%. ConclusionMagnolol， honokiol and lignocellulosic components in MOCD are valuable for development and utilization， the combination of alkaline pretreatment and tween-80 can realize the recovery and utilization of these three resource components， which can provide a new idea for comprehensive utilization of resource components in MOCD.

Objective To explore the risk factors for vascular invasion and its influence on prognosis of resectable gastric cancer patients by analyzing the clinicopathological features. Methods We retrospectively analyzed the data of 1077 patients with stage Ⅰ-Ⅲ gastric cancer who underwent surgical resection. According to whether vascular invasion occurred, they were divided into LVI positive group (n=672) and LVI negative group (n=405). Logistic univariate and multivariate analyses were used for the relation between clinical pathological features and LVI. Survival analysis was used to study the relation between vascular invasion and survival rate in patients with stage Ⅰ gastric cancer. Results Univariate analysis showed that tumor size, type of differentiation, depth of invasion, lymph node metastasis, TNM stage, Lauren classification, nerve invasion and the increase of CEA, CA125 and CA199 were risk factors for vascular invasion (P < 0.05). Multivariate analysis showed that poor differentiation, deep invasion, lymph node metastasis, nerve invasion and elevated CA724 were independent risk factors for vascular invasion. The 5-year survival rate of stage Ⅰ gastric cancer patients with vascular invasion was significantly lower than that without vascular invasion (P < 0.01). Conclusion Gastric cancer patients with poor differentiation, deep invasion, lymph node metastasis, nerve invasion and elevated CA724 are more prone to vascular invasion. Patients with stage I gastric cancer at risk of vascular invasion should be treated more aggressively.

Objective To investigate the application prospect of the most extensive genome engineering pig internationally in preclinical xenotransplantation. Methods Porcine endogenous retrovirus (PERV) knockout combined with 3 major heterologous antigen gene knockouts and 9 humanized genes for inhibition of complement activation, regulation of coagulation disorders, anti-inflammatory and anti-phagocytosis were transferred into a pig (PERV-KO/3-KO/9-TG) as a donor, and the heart, liver and kidney were obtained and transplanted to 3 Rhesus macaque recipients respectively to establish a preclinical research model of pig-to-Rhesus macaque xenotransplantation. The functional status of xenografts after blood flow reconstruction was observed and the survival of recipients was summarized. The hemodynamics of xenografts were monitored. The change of hematological indexes of each recipient was compared. The histopathological manifestation of xenografts was observed. Results After the blood flow was reconstructed, all xenografts showed ruddy color, soft texture and good perfusion. The transplant heart, liver and kidney showed full arterial and venous blood flow and good perfusion at 1 d after operation. The postoperative survival time of heart, liver, and kidney transplant recipients was 7, 26, and 1 d, respectively. The levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase increased in heart transplant recipient at 1 d after operation, and gradually recovered to near normal levels at 6 d after operation. All indexes increased sharply at 7 d after operation. The level of aspartate aminotransferase increased in liver transplant recipients at 2 d after operation, and the alanine aminotransferase basically returned to normal at 10 d after operation, but the total bilirubin continued to increase. Both aspartate aminotransferase and alanine aminotransferase increased at 12 d after operation, and reached a peak at 15 d after operation. The kidney transplant recipient developed mild proteinuria at 1 d after operation, and died of sudden severe arrhythmia. Histopathology showed that the tissue structure of cardiac and renal xenografts was close to normal, and liver xenografts presented with patchy necrosis, the liver tissue structure was disordered, accompanied by inflammatory damage, interstitial hemorrhage and thrombotic microangiopathy. Conclusions PERV-KO/3-KO/9-TG pig shows advantages in overcoming hyperacute rejection, mitigating humoral rejection and coagulation dysregulation. However, whether it can be used as potential donor for clinical xenotransplantation needs further evaluation.

Objective    To investigate the safety and feasibility of laryngeal mask general anesthesia as a replacement of tracheal intubation general anesthesia in the "three-port" thoracoscopic thymectomy via subxiphoid and subcostal arch for thymoma patients without myasthenia. Methods    From January 2018 to June 2019, clinical data of patients with thymoma who underwent the novel "three-port" operation in our institution were analyzed retrospectively. The patients were divided into two groups according to the anesthesia methods, including a tracheal intubation general anesthesia group and a laryngeal mask general anesthesia group. There were 70 patients in the tracheal intubation general anesthesia group, including 42 males and 28 females, with an average age of 45.83±15.89 years. There were 39 patients in the laryngeal mask general anesthesia group, including 26 males and 13 females, with an average age of 43.31±15.64 years. The clinical data of the two groups were compared. Results    The baseline characteristics of the patients in the two groups were well balanced (P>0.05). No massive bleeding, conversion to thoracotomy, postoperative myasthenia or death occurred in those patients. No patient with laryngeal mask anesthesia had a conversion to tracheal intubation anesthesia during the operation. There was no significant difference in the operation time, intraoperative bleeding, intraoperative maximum partial pressure of CO2, lowest partial pressure of oxygen and anesthesia effect score between the two groups (P>0.05). There was also no statistical difference in postoperative aspiration, gastrointestinal discomfort, length of hospital stay, pain score and patient satisfaction degree between the two groups (P>0.05). However, the anesthesia time before operation and the time of awake after anesthesia in the laryngeal mask anesthesia group were significantly shorter than those in the tracheal intubation general anesthesia group (P<0.05), and the incidence of transient arrhythmia, laryngeal discomfort and hoarseness in the laryngeal mask general anesthesia group was significantly lower than that in the tracheal intubation general anesthesia group (P<0.05). Conclusion    The "three-port" thoracoscopic thymectomy via subxiphoid and subcostal arch under laryngeal mask general anesthesia is safe and feasible in the treatment of thymoma without myasthenia, and can be recommended routinely.

Objective To investigate the reasons of HOXA5 overexpression in GBM and the molecular mechanism of miR-128-3p regulating the proliferation, invasion and apoptosis of glioblastoma multiforme. Methods After increasing and decreasing miR-128-3p expression in U87 cell lines by lentivirus transfection, the changes of HOXA5 expression were detected by Western blot, to explore the correlation between miR-128-3p and HOXA5 in GBM. The dual-luciferase reporter tests were performed to detect the target interaction of miR-128-3p with HOXA5. Through CCK-8 test, Transwell test, flow cytometric assay and tumor cell xenograft in nude mice, we verified molecular mechanism of miR-128-3p regulating the proliferation, invasion and apoptosis of GBM in vitro and in vivo. Results The expression level of HOXA5 was decreased in U87 cell line after miR-128-3p upregulation. In addition, the expression level of HOXA5 was increased in U87 cell line after miR-128-3p downregulation (P < 0.05). The expression level of HOXA5 was correlated negatively with the expression of miR-128-3p in U87 cell lines. MiR-128-3p targetedly interacted with 3'UTR of HOXA5 and inhibited the expression of HOXA5. The proliferation, invasion and anti-apoptosis of U87 cells were significantly decreased in the miR-128-3p+control group. Conclusion MiR-128-3p regulates negatively the proliferation, invasion and anti-apoptosis of GBM cells by targeting HOXA5. The overexpression of HOXA5 is induced by downregulation of miR-128-3p in GBM.

Objective To investigate the molecular mechanism of SNHG5 regulating the proliferation, invasion and apoptosis of glioblastoma multiforme (GBM) cells by targeting miR-421. Methods Real-time quantitative PCR test was performed to detect the expression levels of SNHG5 and miR-421 in 31 cases of GBM tissue samples and 32 cases of normal brain tissue samples. After increasing or decreasing SNHG5 expression in U87 cell lines by lentivirus or plasmid transfection, the changes of miR-421 expression were measured by real-time quantitative PCR, to explore the correlation between SNHG5 and miR-421 in GBM. The dual-luciferase reporter test was performed to explore the target interaction of SNHG5 and miR-421. The plasmids with low expression of SNHG5 and miR-421 were cotransfected into U87 cells for the rescue experiment. CCK-8 test, Transwell test, flow cytometry and tumor cell xenograft in nude mice were used to verify molecular mechanism of SNHG5 regulating the proliferation, invasion and apoptosis of GBM in vitro and vivo. Results The expression level of miR-421 was decreased in U87 cell line after SNHG5 upregulation. In addition, the expression level of miR-421 was increased in U87 cell line after SNHG5 downregulation (P < 0.05). The expression level of SNHG5 was correlated negatively with the expression of miR-421 in GBM and U87 cell line. The result of luciferase reporter tests indicated SNHG5 targetedly interacted with miR-421. Rescue experiment results showed that compared with si-SNHG5+miR-421-inhibitor group, the proliferation, invasion and anti-apoptosis ability of U87 cells were significantly inhibited in the si-SNHG5+control-inhibitor group, the expression levels of BAX and p21 were significantly higher, the expression levels of CyclinD1 and Bcl-2 were lower remarkably (P < 0.05). Conclusion SNHG5 promotes the proliferation, invasion and anti-apoptosis of GBM by targeting miR-421 and regulating the expression of CyclinD1, p21, BAX and Bcl-2. Downregulation of miR-421 is related to SNHG5 overexpression in GBM.