Aim To observe the role of salvianolic acid B(Sal B)in enhancing the survival of random skin flaps and to preliminarily explore its potential mecha-nisms.Methods The appearance,degree of edema,color and hair condition of the skin flap were evaluated seven days after operation.The vascular network and blood flow of random flaps were measured by laser Doppler flow measurement.HE staining was used to detect the growth of microvessels in random flaps.The expressions of VEGF and CD34 were detected by im-munohistochemistry,the expressions of RIPK1,2 and LC3 Ⅱ were detected by immunofluorescence,and the effects of autophagy related proteins and signaling path-ways were detected by Western blot.Results The ex-perimental results showed that Sal B induced autophagy in the random skin flaps,promoted angiogenesis,and reduced oxidative stress and necrotic apoptosis,signifi-cantly increasing the survival rate of the flaps.Immu-nohistochemistry,immunofluorescence staining,and Western blot confirmed that Sal B induced autophagy in the random skin flaps by activating TFE3 protein.Conclusion Sal B can promote autophagy in cells of random skin flaps and reduce their necrotic apoptosis by activating TFE3 protein.

OBJECTIVES: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. METHODS: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. RESULTS: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. CONCLUSIONS Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Child, Preschool ; Combined Modality Therapy ; Humans ; Infant ; Neuroblastoma/drug therapy* ; Positron-Emission Tomography ; Radionuclide Imaging ; Retrospective Studies ; Treatment Outcome

AIM:To observe the clinical effect of ranibizumab combined with 577nm micropulse laser in the treatment of severe diabetic macular edema(DME). METHODS:There were 52 eyes of 52 patients diagnosed with severe DME who admitted to the People's Hospital of Guangxi Zhuang Autonomous Region from June 2016 to September 2019. The patients were randomly divided into the observation group(26 patients with 26 eyes, treated with ranibizumab combined with 577nm micropulse laser)and the control group(26 patients with 26 eyes, treated with ranibizumab alone). Patients in both groups received intravitreal injection of ranibizumab with “3+PRN” regimen. Followed up at 9mo after treatment to observe the central macular thickness(CMT), the best corrected visual acuity(BCVA)and the times of intravitreal injection of ranibizumab in the two groups.RESULTS:Compared with before treatment, the CMT and BCVA of the two groups were significantly improved at each time point after treatment(all P<0.001), but there was no difference between the two groups(P>0.05). During the follow-up period, the times of vitreous injection of ranibizumabin the observation group was significantly less than that in the control group(5.88±1.24 times vs 7.12±1.24 times, P=0.001). CONCLUSION:Both ranibizumab combined with 577nm micropulse laser and ranibizumab alone are effective in reducing edema and improving vision in patients with severe DME, but the combination therapy reduces the times of injection.

Aim To explore the mechanism of asiatic acid (AA) on alcoholic hepatitis (AH) based on the network pharmacology and experimental verification in vivo methods. Methods The potential mechanism of AA on AH was explored by data collection, network construction, and enrichment analysis. Meanwhile, the model of alcoholic hepatitis disease was induced by in-tragastric administration of edible alcohol every day in SD rats. The key related indicators were detected, including biochemical markers, inflammatory responses, alcohol metabolism, pathological changes in liver tissues, and the expression of proteins of the NF-kB pathway. Results A total of 24 overlapping targets of AA and AH were screened out, and 20 signaling path ways and 12 GO functional entries were obtained. This study focused on the first pathway, hsa05200; Pathways in cancer. The pathway contained NF-kB signaling pathway. In vivo results showed that AA significantly reduced the serum levels of ALT and AST, increased the levels of alcohol metabolism and decreased the liver content of TNF-a and GSH. Additionally, AA significantly inhibited p-IKKa/(3, p-Ii

Objective: To compare the efficacy, advantages and disadvantages of endoscopic CO₂ laser cauterization (ECLC) and open neck surgery in the treatment of congenital pyriform sinus fistula (CPSF). Methods: From September 2014 to March 2017, 80 cases with confirmed diagnosis of CPSF received initial treatment at Guangdong Provincial People's Hospital were prospectively analyzed, including 34 males and 46 females, aged 18 to 672 (194.17±141.18) months. They were consecutively divided into endoscopic group and open-surgery group, with 40 cases in each group. Both groups of patients received surgical treatment under general anesthesia. The endoscopic group was treated by endoscopic CO₂ laser cauterization, and the open-surgery group underwent the following surgery: first, we performed suspension laryngoscopy examination to confirm the presence of fistula in the bottom of the piriform fossa, then open-neck resection of congenital piriform sinus fistula with recurrent laryngeal nerve and/or lateral branch of superior laryngeal nerve anatomy plus partial thyroidectomy were performed. The data between the two groups were compared, including the operative time, intraoperative blood loss, postoperative pain, average length of stay, neck cosmetic scores, complications and cure rates. All patients were followed up in outpatient clinics. Statistical analysis was performed using SPSS 20.0 software. P<0.05 indicates that the difference is statistically significant. Results: All patients were successfully completed the operation. The operative time, intraoperative blood loss, postoperative pain and average length of hospital stay in the endoscopic group were significantly less than those in the open group [(27.4±5.5) min to (105.8±52.5) min, (0.6±0.5) ml to (33.6±41.5) ml, (1.7±0.9) points to (4.6±0.7) points, (5.9±2.9)d to(8.9±3.3)d, t values were-9.400, -5.031, -16.199, -4.293, P values were all<0.01]; The neck cosmetic score in the endoscopy group was significantly greater than that of the open group [(9.9±0.4) against (5.8±0.9) points, t=25.847, P<0.01]. Compared with the open group (15.0%, 6/40), the complication rate of the endoscopic group (7.5%, 3/40) was not statistically significant (χ²=0.50, P>0.05). Three months after the first treatment, the cure rate in the endoscopic group (82.5%, 33/40) was significantly lower than that in the open-neck group (100.0%, 40/40), χ²=5.64, P<0.05. The follow-up time was 12 months after the last treatment. Eighty cases were followed up and none was lost to follow-up. During the follow-up period, the cure rate of the endoscopy group (97.5%, 39/40) was compared with that of the open group (100.0%, 40/40), and the difference was not statistically significant. Conclusions: In the treatment of CPSF, the two-surgical method each has their advantages. Compared with open-neck surgery, ECLC is simpler, repeatable. ECLC has shorter time in operation and hospital stay, less complications, and less postoperative pain and more precise cosmetic results. It could be preferred for the initial treatment of CPSF and relapsed cases after cauterization. But subject to relatively low cure rate of one-time cauterization and uncertain long-term efficacy, it cannot completely replace the open-neck surgery at present.
Carbon Dioxide ; Cautery ; Endoscopy ; Female ; Fistula/surgery* ; Humans ; Lasers, Gas/therapeutic use* ; Male ; Pyriform Sinus/surgery* ; Retrospective Studies ; Treatment Outcome

Hemorrhagic transformation (HT) is a common complication of ischemic stroke, especially after thrombolytic therapy, which is associated with increased morbidity and mortality. Thrombolysis with tissue plasminogen activator (t-PA) increases the rate of HT by as much as 10-fold, and the mortality by about 60%. The patients who are eligible for t-PA treatment are still between 3.4% and 5.2% of all patients with acute ischemic stroke because of the narrow therapeutic time window. Due to the unknown mechanism and therapeutic target of HT, there are no effective drugs to decrease the incidence of HT. The main mechanism of HT is disruption of the blood-brain barrier (BBB) integrity and neurovascular homeostasis, involving a variety of molecular signaling pathways. In animal and clinical studies, combining therapeutic agents with t-PA, which may help to minimize BBB perturbations, reduces the incidence of HT and increases the safety of thrombolytic therapy. This article is prepared to review the mechanisms, targets and therapeutic drugs of t-PA induced HT in recent years to provide a reference to the basic research and drug development of HT.

In this paper, the status of adjuvant standard for Chinese materia medica processing in the Chinese Pharmacopoeia 2015 edition, the National Specification of Chinese Materia Medica Processing, and the 29 provincial specification of Chinese materia medica was summarized, and the the status including general requirements, specific requirements, and quality standard in the three grade official specifications was collected and analyzed according to the "medicine-adjuvant homology" and "food-adjuvant homology" features of adjuvants. This paper also introduced the research situation of adjuvant standard for Chinese materia medica processing in China; In addition, analyzed and discussed the problems existing in the standard system of adjuvant for Chinese materia medica processing, such as lack of general requirements, low level of standard, inconsistent standard references, and lack of research on the standard, and provided suggestions for the further establishment of the national standards system of adjuvant for Chinese materia medica processing.

BACKGROUND:The roles of osteocyte and osteoblast apoptosis in steroid-induced avascular necrosis of the femoral head (ANFH) have arouse much attention,and its pathogenesis has been understood gradually.But there is a lack of knowledge about the mechanisms underlying osteocyte and osteoblast apoptosis.Meanwhile,hormones have been shown to enhance the Dickkopf-1 expression in Wnt signaling pathway.OBJECTIVE:To investigate the roles of Dickkopf-1 and cell apoptosis in steroid-induced ANFH,and to understand their correlations with steroid-induced ANFH.METHODS:Necrotic femoral head samples were removed from 14 patients with steroid-induced ANFH after total hip arthroplasty (experimental group),and normal femoral heads were from 8 patients with femoral neck fracture (control group).The cellular morphology was observed using transmission electron microscope;the number of empty lacunae was counted through hematoxylin-eosin staining;the cell apoptosis was detected by TUNEL assay;the expression level of Dickkopf-1 was detected by immunohistochemistry.Moreover,the correlation between the Dickkopf-1 positive rate and apoptosis index of osteocytes was analyzed by Spearman rank correlation analysis.RESULTS AND CONCLUSION:The number of empty lacunae,expression level of Dickkopf-1,and apoptosis index of osteocytes in the experimental group were significantly higher than those in the control group (P ＜ 0.05).In the experimental group,the Dickkopf-1 positive rate was positively correlated to the apoptosis index of osteocytes (r=0.623).These results indicate that Dickkopf-1 and osteocyte apoptosis both play key roles in steroid-induced ANFH,and increased Dickkopf-1 level may promote the development of ANFH.

Objective To investigate the effect and molecular mechanisms of phosphatidylinositol-3 kinase(PI3K)inhibitor ZSTK474 on human melanoma A375 cells in vitro. Methods The effect of ZSTK474 on the proliferation of A375 cells was deter?mined by MTT assay.Flow cytometric analysis was carried out to examine effect of ZSTK474 on the cell cycle of A375 cells.Western-blot was conducted to evaluate the effect of ZSTK474 on the expression of the cell cycle related proteins,cyclin B1 and cdc2.Chou-Talalay method was used to evaluate the combination of ZSTK474 with PD0332991.Results In the MTT assay,ZSTK474 inhibited the proliferation of A375 cells in a dose-dependent manner with the IC50value of 1.535 μmol/L.Furthermore,ZSTK474 arrested the cell cycle progression of the A375 cells at the G2/M phase via downregulating the expression of cyclin B1 and cdc2 at 1 and 5 μmol/L. In the synergistic assay,the combination of ZSTK474 with PD0332991 in the ratio 8×IC50 ZSTK474:1×IC50 PD0332991showed a synergistic ef?fect,with the combination index(CI)values of 0.463 ± 0.113,0.658 ± 0.009 and 0.941 ± 0.034 for ED50、ED75and ED90,respectively. Conclusion ZSTK474 could inhibit the proliferation of A375 cells and arrest the cell cycle at the G2/M phase.The combination of ZSTK474 with PD0332991 could exert a synergistic effect.The precent result has revealed that the PI3K inhibitor ZSTK474 is likely to be applied alone or in combination with the CDK4/6 inhibitor PD0332991 for the human melanoma therapy.

The chinmedomics method was used to explore the effect of Nanshi capsule on endogenous metabolites of rats with kidney-yang deficiency syndrome, investigate the metabolites and metabolic pathways closely related to kidney-yang deficiency syndrome (KYDS)and identify the therapeutic basis of Nanshi capsule(NPC)as well as its action mechanism for KYDS. The routine biochemical indexes of serum were detected and histomorphology was observed. Based on the chinmedomics technology platform, discriminatory analysis in multivariate modes was conducted for rat blood and urine, thus to investigate the biomarkers of KYDS and the therapeutic effect of NPC against KYDS. Meanwhile, the main constituents of NPC in rat serum were also detected to analyze its correlation between the constituents in vivo and the biomarkers of KYDS, and determine the potential effective compounds for therapeutic effect. Eleven biomarkers of KYDS were identified in the rat models, involving steroid hormone biosynthesis, tryptophan metabolism and tyrosine metabolism. It was found that NPC could regulate steroid hormone biosynthesis, tryptophan metabolism and tyrosine metabolism; PCMS analysis showed that caffeic acid, 2-hydroxy-1-methoxy-anthraquinone, 1-hydroxy-2-methoxyanthraquinone, ferulic acid glucuronide conjugation, deacetylasperulosidic acid, cynaroside, betaine and umbelliferone were the main effective compounds of NPC for KYDS. In this study, cynaroside, betaine, umbelliferone and other compounds in NPC could integrally regulate the disturbance of metabolic profile in KYDS by improving the hormone synthesis, hormone synthesis pathway, hormone synthesis and release pathway in tyrosine metabolism and linoleic acid synthesis pathway in linoleic acid metabolism. These results indicated that the NPC had the characteristics of multi-pathway, multi-target and overall regulation in the treatment of KYDS. Chinmedomics approach can provide methodology support to discover innovative drug from traditional Chinese medicine.