Application of organoids in basic research and clinical translation of cancers / 天津医药

Organoids are the three-dimensional culture of adult stem cells or pluripotent stem cells in vitro to form tissue analogs with specific structures,which have highly similar tissue properties and physiological functions to the corresponding organs.The emergence of organoid technology has laid an important foundation for research in organ development,disease modeling and drug discovery.Tumor organoid,as an important branch of organoids,is a transition between cell lines and animal models,which can well retain the histological and mutational characteristics of tumors in patients and play an essential role in building tumor organoid sample libraries,reconstructing tumor microenvironment,studying the tumor development mechanism as well as formulating personalized treatment plans and drug screening.Tumor organoids help clinicians to realize precise treatment for patients.However,some factors still limit the further development of tumor organoids,such as the lack of microenvironmental components,vascular structure,high culture cost and technical difficulties.In this review,we summarize the applications and challenges of organoid technology in basic tumor research and clinical translation and look forward to the future development of tumor organoids.

Application of core-shell structured nanofibers in oral tissue regeneration / 中国组织工程研究

BACKGROUND:The combination of good biomechanical properties,controlled drug release and multi-functionality of core-shell structured nanofibers is receiving more and more attention,which also makes them promising for a wide range of applications in the field of oral tissue regeneration. OBJECTIVE:To summarize the preparation,drug loading and release mechanisms of core-shell structured nanofibers and their application in the regenerative repair of oral tissues. METHODS:A computer search of the literature collected in CNKI and PubMed from January 2000 to November 2022 was applied,and the search terms in English and Chinese were"electrospinning,core-shell structures,drug delivery systems,jaw bone regeneration,cartilage regeneration,periodontal tissue regeneration". RESULTS AND CONCLUSION:(1)There are various methods for the preparation of core-shell structured nanofibers,but the coaxial and emulsion methods of electrostatic spinning have unique advantages such as simple operation,diverse material selection and good biocompatibility.(2)Core-shell structured nanofibers can be used as bacteriostatic agents,carriers of different types of drugs,and scaffolds for cell adhesion,providing new therapeutic options for oral tissue regeneration.(3)Controlled degradation and drug release rate of core-shell structured nanofibers can better adapt to the healing process of oral tissue defect repair and achieve ideal tissue regeneration.

Effects of Peripheral Blood Stem Cell Transplantation from Haploidentical Versus Matched Sibling Donors on High-risk and Refractory/Relapsed Acute Myeloid Leukemia / 肿瘤防治研究

Objective To investigate the clinical efficacy of peripheral blood stem cell transplantation from haploidentical and matched sibling donors for treatment of high-risk and refractory/relapsed acute myeloid leukemia (AML). Methods Data on the efficacy of haploidentical peripheral blood stem cell transplantation (Haplo-HSCT) with myeloablative conditioning regimen were retrospectively analyzed and compared with that of matched sibling donors' peripheral blood stem cell transplantation (MSD-HSCT) for treatment of high-risk refractory/relapsed AML in our center from January 1st, 2010 to June 30th, 2020. Results A total of 98 patients were enrolled, including 62 patients in the Haplo-HSCT group and 36 patients in MSD-HSCT group. The median age, conditioning regimen, and infusion doses of MNC and CD34+ cells were significantly different between the two groups, but no significant differences in other baseline parameters were found. Transplantation-related infectious complications and the incidence of acute and chronic graft-versus-host disease (GVHD) were also not significantly different between the two groups. The 3-year cumulative relapse in the Haplo-HSCT group was significantly lower than that in the MSD-HSCT group (16.2% vs. 41.1%, P=0.036). The 3-year DFS of the Haplo-HSCT and MSD-HSCT groups were 66.98% and 41.8%, respectively (P=0.140), and their OS were 73.37% and 51.41%, respectively (P=0.105). Conclusion The clinical efficacy of Haplo-HSCT for the treatment of high-risk and refractory/relapsed AML is similar to that of MSD-HSCT, and Haplo-HSCT may have better GVL effect.

Efficacy observation of high-dose non-T-cell depleted PBSC used as grafts for haploidentical HSCT with reduced intensity conditioning in elderly patients with AML/MDS / 白血病·淋巴瘤

Objective:To investigate the clinical efficacy of high-dose non-T-cell depleted peripheral blood stem cells (PBSC) used as grafts in haploidentical hematopoietic stem cell transplantation with reduced intensity conditioning (RIC-haplo-HSCT) in the treatment of elderly patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).Methods:The clinical data of AML or MDS 28 patients aged ≥50 years who underwent RIC-haplo-HSCT in the First Affiliated Hospital of Xinjiang Medical University from January 2014 to June 2022 were retrospectively analyzed. All patients received high-dose non-T-cell depleted PBSC as grafts. Anti-CD25 monoclonal antibody and glucocorticoid were added as intensive graft-versus-host disease (GVHD) prophylaxis.Results:All patients achieved hematopoietic reconstruction. The accumulative incidence of grade Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD within 100 d was 22.5% (95% CI 5.1%-39.9%) and 8.2% (95% CI 0-19.2%), respectively. The 3-year cumulative incidence of chronic GVHD was 26.8% (95% CI 7.8%-45.8%), and the incidence of extensive chronic GVHD was 5.9% (95% CI 0-17.1%). The median follow-up time was 35.5 (2-83) months. The 3-year cumulative incidence of relapse and non-relapse mortality was 16.7% (95% CI 2.0%-31.9%) and 12.2% (95% CI 0-25.2%), respectively. The 3-year disease-free survival and overall survival rates were 73.3% (95% CI 56.2%-90.4%) and 79.1% (95% CI 62.2%-96.0%), respectively. Conclusions:High-dose non-T-cell depleted PBSC used as grafts for RIC-haplo-HSCT can achieve good clinical efficacy in elderly patients with AML/MDS.

Relationship between non-high density lipoprotein cholesterol and leptomeningeal collaterals in patients with acute middle cerebral artery occlusion / 实用医学杂志

Objective To explore the relationship between non-high density lipoprotein cholesterol(non-HDL-C)level and leptomeningeal collateral circulation in patients with acute middle cerebral artery occlusion.Methods A total of 85 patients with first-onset acute cerebral infarction with middle cerebral artery M1 segment occlusion were enrolled.According to the results of DSA,LMC circulation was assessed by American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology Collateral Circulation Assess-ment System.All patients were assigned to better LMC circulation group(score 2～4,n = 30)and worse LMC circulation group(score 0～1,n = 55),and the levels of non-HDL-C were compared between the two groups.Results The levels of LDL-C and non-HDL-C in worse LMC circulation group were significantly higher than those of the better LMC circulation group(P = 0.026,P = 0.010).non-HDL-C was an independent risk factor for the worse LMC circulation(OR = 3.019,95%CI:1.053～8.658,P = 0.04).LMC circulatory score of patients was negatively correlated with the levels of non-HDL-C level(r =-0.228,P = 0.036).The AUC of non-HDL-C predicted for the worse LMC circulation was 0.638(95%CI:0.521～0.755,P = 0.036).Conclusions non-HDL-C in patients with acute cerebral infarction was significantly related to worse LMC circulation,and was a risk factor for worse LMC circulation.It is suggested that the higher expression of non-HDL-C could be used to predict worse LMC circulation as a serological indicator.

Acceptance testing and clinical assessment of the in-vivo dose measurement EPIgray system / 中国医学装备

Objective:To assess the accuracy of dose reconstruction of the in-vivo dose verification EPIgray system in intensity-modulated radiation therapy(IMRT)and volumetric-modulated arc therapy(VMAT)through acceptance testing,and to explore the preliminarily clinical application of that.Methods:A total of 37 patients with cancer at various parts were selected for clinical testing.Referring to the suggestions of the acceptance manual of manufacturer and the American Association of Physicists in Medicine(AAPM)TG-119 report,the square field,strip field and intensity-modulated plan were adopted to test the precision of dose reconstruction of EPIgray system on phantom.The recognition ability of the system for error was researched through changed the thickness of homogeneous phantom and the skin distance of exposure source.A total of 37 patients with cancer at different parts who underwent VMAT were selected to conduct clinical test,and then,the consistence between the dose reconstruction of EPIgray system and the counted dose of treatment plan system were further analyzed.Results:In the tests of square field,EPIgray dose reconstruction demonstrated excellent linearity and higher accuracy.On the phantoms with different thicknesses of fields with different sizes,the highest precision of dose reconstruction of central axis of field was(0.10±0.39)%.The all precisions of dose reconstruction were within 3.0%besides the built region of dose and field edges.In the tests of IMRT and VMAT plan,the deviation of dose reconstruction was<5.0%.With the increasing of the complexity of plan and the heterogeneity of phantom,there was a slight decrease in the reconstruction precision,but all deviations of dose reconstruction were within the range of allowable deviations.In clinical testing of 37 patients,the average reconstruction deviation of the prescription dose point was(-0.6±4.8)%,and the average deviation of sampling points within the range of target area was(-2.1±2.7)%.The reconstruction deviations outside of field and that with large dose gradient were larger.Conclusion:The dose reconstructions of in-vivo dose verification system EPIgray has better consistency with treatment planning system in calculating dose,and the precision of dose reconstruction can meet the requirement of clinical application.

Repair and regeneration of myocardial fibroblasts after myocardial injury and regulation by traditional Chinese medicine / 中国药理学通报

Cardiomyocytes are highly differentiated terminal cells with poor self-renewal ability. Therefore, after myocardial infarction necrotic cardiomyocytes cannot be effectively replenished, and the infarcted area is quickly replaced by fibrous tissue, which seriously affects cardiac function. The reduction of the number of myocardial cells and the destruction of the structural integrity of the heart have caused cardiovascular diseases such as myocardial infarction and heart failure, which continue to endanger human life and health. At present, the treatment of coronary heart disease has made great progress. The commonly used treatment options for myocardial repair after myocardial infarction mainly include stem cell transplantation, exosome mediation and microenvironment construction, but all of them are difficult to solve to varying degrees. Cardiac fibroblasts occupy the majority of cardiac cells, and the distribution characteristics of fibroblasts and their role in the process of myocardial infarction make them important effector cells after myocardial infarction. Therefore, this article reviews the source, distribution, post-infarction status of myocardial fibroblasts and the effect of fibroblasts on cardiomyocytes, in order to provide new treatment ideas and solutions for fibroblasts in the repair and regeneration of myocardial cells after myocardial infarction.

Treatment of intravesical instillation with fulguration-hydrodistention on female interstitial cystitis / 北京大学学报(医学版)

OBJECTIVE@#To investigate the efficacy and safety of intravesical instillation of heparin/alkalized lidocaine (lidocaine mixed with sodium bicarbonate) combined with hydrodistension and transurethral fulguration in the treatment of female interstitial cystitis (IC).@*METHODS@#Female patients who attended the Department of Urology at the First Hospital of China Medical University between January 2012 and December 2020 and met the diagnostic criteria proposed in the guidelines of the American Urological Association with a new diagnosis of IC were selected for retrospective analysis. Cystoscopy and biopsy of suspicious lesions were performed at the time of diagnosis. All the patients were treated with an intravesical instillation regimen of 2% lidocaine 10 mL + 5% sodium bicarbonate 5 mL + heparin 25 000 IU for a continuous period of 12 months, with or without water dilatation and transurethral electrocautery according to the patient's preference, categorized as hydrodistension and transurethral fulguration (HD/TF) group and non-HD/TF group. The patients were evaluated before and 1, 6, and 12 months after treatment for O'Leary-Sant interstitial cystitis patient symptom index scores (ICSI), interstitial cystitis patient problem index scores (ICPI), visual analog scale (VAS) of suprapubic pain, and functional bladder capacity (FBC) changes.@*RESULTS@#A total of 79 patients were collected in this study. Four (5.1%) of these patients underwent cystectomy due to pathological diagnosis of cancer or treatment failure. The remaining patients were followed up 1, 6 and 12 months after treatment. Repeated-measures ANOVA showed a significant decrease in ICPI, ICSI and VAS and an increase in FBC after treatment compared with before treatment (P < 0.05). FBC continued to decrease during the 1, 6 and 12 months' post-treatment follow-ups, with statistically significant differences; ICSI continued to decrease during the 1 and 6 months post-treatment follow-ups, with statistically significant differences, while the difference between ICSI at 6 months post-treatment and at 12 months' post-treatment was not statistically significant. In the HD/TF group, ICPI continued to decrease in the follow-up from 1 and 6 months after treatment, and the difference was statistically significant, while the difference between ICPI 6 months after treatment and 12 months after treatment was not statistically significant. There was no statistically significant difference between the remaining indicators 1, 6 and 12 months after treatment. ICPI, ICSI, VAS and FBC improved earlier and the changes in VAS and FBC were more significant in the HD/TF group compared with the non-HD/TF group (P < 0.05).@*CONCLUSION@#Heparin/alkalized lidocaine combination of intravesical instillation with hydrodistension and transurethral fulguration for IC is an effective treatment option. Heparin/alkalized lidocaine combination of intravesical instillation may be the first choice of treatment, which can significantly reduce the economic burden of patients and medical insurance system. If patients can accept it, transurethral fulguration with hydrodistension may be considered.

Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research / 中华血液学杂志

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

Feasibility study of using bridging temporary permanent pacemaker in patients with high-degree atrioventricular block after TAVR / 中华心血管病杂志

Objective: To determine the feasibility of using temporary permanent pacemaker (TPPM) in patients with high-degree atrioventricular block (AVB) after transcatheter aortic valve replacement (TAVR) as bridging strategy to reduce avoidable permanent pacemaker implantation. Methods: This is a prospective observational study. Consecutive patients undergoing TAVR at Beijing Anzhen Hospital and the First Affiliated Hospital of Zhengzhou University from August 2021 to February 2022 were screened. Patients with high-degree AVB and TPPM were included. Patients were followed up for 4 weeks with pacemaker interrogation at every week. The endpoint was the success rate of TPPM removal and free from permanent pacemaker at 1 month after TPPM. The criteria of removing TPPM was no indication of permanent pacing and no pacing signal in 12 lead electrocardiogram (EGG) and 24 hours dynamic EGG, meanwhile the last pacemaker interrogation indicated that ventricular pacing rate was 0. Routinely follow-up ECG was extended to 6 months after removal of TPPM. Results: Ten patients met the inclusion criteria for TPPM, aged (77.0±11.1) years, wirh 7 females. There were 7 patients with third-degree AVB, 1 patient with second-degree AVB, 2 patients with first degree AVB with PR interval>240 ms and LBBB with QRS duration>150 ms. TPPM were applied on the 10 patients for (35±7) days. Among 8 patients with high-degree AVB, 3 recovered to sinus rhythm, and 3 recovered to sinus rhythm with bundle branch block. The other 2 patients with persistent third-degree AVB received permanent pacemaker implantation. For the 2 patients with first-degree AVB and LBBB, PR interval shortened to within 200 ms. TPPM was successfully removed in 8 patients (8/10) at 1 month without permanent pacemaker implantation, of which 2 patients recovered within 24 hours after TAVR and 6 patients recovered 24 hours later after TAVR. No aggravation of conduction block or permanent pacemaker indication were observed in 8 patients during follow-up at 6 months. No procedure-related adverse events occurred in all patients. Conclusion: TPPM is reliable and safe to provide certain buffer time to distinguish whether a permanent pacemaker is necessary in patients with high-degree conduction block after TAVR.

Pathological evaluation of 30 cases of esophageal squamous cell carcinoma after two neoadjuvant therapies / 中华放射肿瘤学杂志

Objective:To explore the pathological differences of surgically resected specimens of advanced esophageal squamous cell carcinoma (ESCC) to different neoadjuvant therapies (neoadjuvant radiochemotherapy and toripalimab combined with neoadjuvant radiochemotherapy).Methods:Thirty patients diagnosed with advanced ESCC who underwent surgical operation after neoadjuvant therapy in Jiangsu Cancer Hospital from October 2020 to September 2021 were included. Among them, 15 patients received neoadjuvant radiochemotherapy (radiochemotherapy group) and 15 patients were treated with toripalimab combined with radiochemotherapy (immunotherapy combined with radiochemotherapy group). Surgically resected specimens were collected. The histopathological features of primary esophageal lesions and the responses of involved lymph nodes were analyzed and compared between two groups.Results:The major pathological response (MPR) rate in the radiochemotherapy group was 10/15, and 14/15 in the immunotherapy combined with radiochemotherapy group ( P=0.17). The pathological complete response (pCR) rate of the primary lesions in the radiochemotherapy group was 7/15, and 10/15 in the immunotherapy combined with radiochemotherapy group ( P=0.46). In the radiochemotherapy group, the incidence rate of tertiary lymphoid structure (TLS) was 7/15, and 12/15 in the immunotherapy combined with radiochemotherapy group ( P=0.02). The incidence rate of necrosis in the radiochemotherapy group was 6/15, and 1/15 in the immunotherapy combined with radiochemotherapy group ( P=0.03). In addition, the incidence rate of foam cell infiltration in the radiochemotherapy group was 6/15, and 13/15 in the immunotherapy combined with radiochemotherapy group ( P=0.01). Furthermore, the pCR rate of involved lymph nodes in the radiochemotherapy group was 7/33, and 11/12 in the immunotherapy combined with radiochemotherapy group ( P<0.001). Conclusion:Compared with the radiochemotherapy group, the incidence of TLS and foam cell infiltration is higher, the incidence of necrosis is lower and clinical efficacy of involved lymph nodes is higher in the immunotherapy combined with radiochemotherapy group, prompting that toripalimab combined with neoadjuvant radiochemotherapy exert higher synergistic immune effect.

Exploring the common mechanism of Yindan Xinnaotong soft capsule in the treatment of stroke and coronary heart disease through HIF1α-MMP9-mediated HIF1α signaling pathway / 药学学报

Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".

Improvement effects and its mechanism of catalpol on testicular lesions in KK-Ay spontaneous diabetic mice by regulating glycolysis / 中国药房

OBJECTIVE To study the improvement effects and its mechanism of catalpol on testicular lesions in KK-Ay spontaneous diabetic mice on the basis of glycolysis process mediated by advanced glycation end products （AGEs） and their receptors （RAGE）. METHODS KK-Ay spontaneous diabetic mice fed with high-fat diet were used as diabetic model， and then randomly divided into model group， catalpol group （100 mg/kg）， aminoguanidine group （AGEs inhibitor， 100 mg/kg） and FPS- ZM1 group （RAGE inhibitor， 1 mg/kg）， and C57BL/6J mice fed in the same period were set as normal group， with 6 mice in each group. The catalpol group and aminoguanidine group mice were given relevant medicine intragastrically， normal group and model group mice were given constant volume of normal saline intragastrically， and FPS-ZM1 group mice were given relevant medicine 1 mL/g intraperitoneally， for consecutive 8 weeks. After the last administration， the body mass， fasting blood glucose， 24-hour food intake， water consumption， urine volume， testicular organ coefficient， and sperm motility of the mice were measured； pathological morphology and ultrastructural structure of testicular tissue were observed； the levels of reduced glutathione （GSH）， superoxide dismutase （SOD）， lactate dehydrogenase （LDH） and sugar metabolites in testicular tissue of mice were detected； pathway enrichment analysis was performed； the level of AGEs in serum and testicular tissue， protein expressions of RAGE， B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）， and mRNA expressions of key rate-limiting enzymes [hexokinase （HK）， phosphofructose kinase （PFK）， pyruvate kinase （PK）， LDH] in testicular tissue were alldetected. RESULT S Catalpol could significantly improve the general symptoms， testicular organ coefficients and motility ofsperm in KK-Ay spontaneous diabetic mice （P＜0.05 or P＜0.01）. The morphology and ultrastructure of spermatogenic cells in each layer of the seminiferous tubules were all improved. The levels of GSH， SOD and LDH in testicular tissue，the levels of the metabolic product glucose fructose-1，6-diphosphate， 3-phosphate glycerate， 3-phosphate glyceraldehyde， lactic acid and pyruvate， the expressions of HK， PFK， PK and LDH mRNA were all significantly increased（P＜0.05 or P＜0.01）； the levels of AGEs in serum and testicular tissue， the expression of RAGE protein and the ratio of Bax to Bcl-2 in testicular tissue were significantly decreased（P＜0.05 or P＜0.01）. Aminoguanidine and FPS-ZM1 could significantly improve the levels of most of above indicators in mice（P＜0.05 or P＜0.01）. CONCLUSIONS Catalpol shows significant improvement effects on testicular lesions of KK-Ay spontaneous diabetic mice， and its mechanism of action was associated with upregulation of AGEs/RAGE signaling pathway- mediated glycolysis.

Fibrocartilaginous mesenchymoma: a clinicopathological analysis of four cases / 中华病理学杂志

Objective: To investigate the clinical, radiological, histological and molecular features and the differential diagnosis of fibrocartilaginous mesenchymoma (FM). Methods: Four cases of FM diagnosed in the Department of Pathology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine from 2020 to 2022 were analyzed. Related literature was also reviewed. Results: Case 1 was a 10-year-old girl with bone destruction in the sacrum and L5 articular processes revealed by CT scan. Case 2 was a 7-year-old girl with an aggressive lesion in her right distal ulna. Case 3 was an 11-year-old boy with a lesion in the metaphysis of his left proximal tibia. Case 4 was an 11-year-old boy with bone destruction in the distal portion of a radius. Microscopically, the four tumors all consisted of numerous spindle cells, hyaline cartilage nodules, and bone trabeculae. The hypocellular to moderately cellular spindle cell component contained elongated cells with slightly hyperchromatic, mildly atypical nuclei arranged in bundles or intersecting fascicles. Benign-appearing cartilaginous nodules of various sizes and shapes were scattered throughout the tumors. There were areas mimicking epiphyseal growth-plate characterized by chondrocytes arranged in parallel columns and areas of enchondral ossification. The stroma was rich in mucus in case 1. Mutation of GNAS and IDH1/IDH2 and amplification of MDM2 gene were not found in any of the three tested cases. Conclusions: FM is very rare and tends to affect young patients. It most frequently occurs in the metaphysis of long tubular bones, followed by the iliac-pubic bones and vertebrae. FM is characterized by a mixed population of spindle cells, hyaline cartilage nodules and trabeculae of bone, without specific immunophenotypes and molecular alternations. As a borderline, locally aggressive neoplasm, surgical removal with a wide margin is generally the treatment of choice for FM.

Progress in omics research and preclinical models of gallbladder cancer / 中华外科杂志

Gallbladder cancer(GBC)is one common type of bile tract cancers with poor prognosis. This review summarizes the recent development of studies about somatic mutation, molecular subtype, microenvironment heterogeneity, organoid, orthotopic model, patient-derived xenograft and clinical translation on GBC in aspects of genomic,transcriptome,single cell omics and clinical translation. We expect this review will provide new ideas on dissecting molecular mechanisms underlying the development and emerging chemoresistance of GBC following therapy and promote GBC precision medicine.

Etiological diagnostic value of metagenomic next-generation sequencing in peritoneal dialysis-related peritonitis / 中华肝脏病杂志

Objective: To explore the etiological diagnostic value of metagenomic next-generation sequencing (mNGS) in peritoneal dialysis (PD)-related peritonitis. Methods: The study was a retrospective cohort study. The clinical data of patients with PD-related peritonitis who were treated and underwent microbial cultivation and mNGS test at the same time from June 2020 to July 2021 in the Affiliated Drum Tower Hospital, Medical School of Nanjing University were analyzed. The positive rate, detection time and consistency between mNGS test and traditional microbial culture were compared. Results: A total of 18 patients with age of (50.4±15.4) years old and median dialysis time of 34.0 (12.4, 62.0) months were enrolled in the study, including 11 males and 7 females. Pathogenic microorganisms were isolated in 17 patients by mNGS test, with a positive rate of 17/18, which was higher than 13/18 of microbial culture, but the difference was not statistically significant (P=0.219). Both mNGS test and microbial culture isolated positive pathogenic bacteria in 12 patients, and mNGS test isolated the same types of pathogenic bacteria as microbial cultivation did in 11 patients. In five patients with negative microbial culture, mNGS test also isolated pathogenic microorganisms, including 3 cases of Staphylococcus epidermidis, 1 case of Mycobacterium tuberculosis and 1 case of Ureaplasma urealyticum. In 1 patient, microbial culture isolated pathogenic bacteria (Escherichia coli) whereas mNGS test did not. The detection time of mNGS was 25.0 (24.0, 27.0) h, which was significantly shorter than 89.0 (72.8, 122.0) h of microbial culture (Z=3.726, P<0.001). Conclusions: mNGS test can improve the detection rate of pathogenic microorganisms in PD-related peritonitis and greatly shorten the detection time, and has good consistency with microbial culture. mNGS may provide a new approach for pathogen identification of PD-related peritonitis, especially refractory peritonitis.

Research progress of occupational hazards in plywood manufacturing / 中华劳动卫生职业病杂志

Occupational disease hazards in plywood manufacturing mainly include wood dust, formaldehyde, phenol, ammonia, noise, terpene, microorganisms, etc. The exposure is complex with multiple factors accompanied or coexisted. In the production process, these factors are exceeded, and mass occupational disease hazard events occurred among workers. Exposure to wood dust, formaldehyde, terpene, etc., put workers at increased risk of cancer. This article provides a review of this issue in order to provide a scientific basis for the prevention and control of occupational disease hazards in plywood manufacturing.

Percutaneous hollow screw internal fixation combined with cementoplasty in treatment of periacetabular metastasis / 中国修复重建外科杂志

OBJECTIVE@#To explore the percutaneous hollow screw internal fixation combined with cementoplasty in the treatment of periacetabular metastasis.@*METHODS@#A retrospective study was performed on 16 patients with periacetabular metastasis who were treated with percutaneous hollow screw internal fixation combined with cementoplasty between May 2020 and May 2021. There were 9 males and 7 females. The age ranged from 40 to 73 years, with an average of 53.6 years. The tumor involved around the acetabulum, and 6 cases were located on the left and 10 cases on the right. Operation time, frequency of fluoroscopy, bed rest time, and complications were recorded. Before operation, and at 1 weeks, 3 months after operation, the visual analogue scale (VAS) score was used to evaluate the pain degree, the short-form 36 health survey scale (SF-36) score was used to evaluate the quality of life. At 3 months after operation, the Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate the functional recovery of patients. During follow-up, the loosening of internal fixator and bone cement leakage were observed by X-ray film.@*RESULTS@#All patients were performed operation successfully. The operation time ranged from 57 to 82 minutes, with an average of 70.4 minutes. The frequency of intraoperative fluoroscopy was 16-34 times, with an average of 23.1 times. After operation, 1 case of incision hematoma and 1 case of scrotal edema occurred. All patients felt the pain relieved after operation. The patients started walking at 1-3 days after operation, with an average of 1.4 days. All patients were followed up 6-12 months (mean 9.7 months). The VAS and SF-36 scores significantly improved after operation when compared with the preoperative scores, and the scores at 3 months after operation were significant better than those at 1 week after operation ( P<0.05). At 3 months after operation, the MSTS score ranged from 9 to 27, with an average of 19.8. Among them, 3 cases were excellent (18.75%), 8 cases were good (50%), 3 cases were fair (18.75%), and 2 cases were poor (12.5%). The excellent and good rate was 68.75%. And 11 patients returned to normal walking, 3 had mild claudication, and 2 had obvious claudication. Radiological examination showed that there were 2 cases of bone cement leakage after operation, and there was no internal fixator loosening or displacement.@*CONCLUSION@#Percutaneous hollow screw internal fixation combined with cementoplasty can effectively relieve pain and improve the quality of life of patients with periacetabular metastasis.

Dorsal plate assisted fixation of dorsal lunate fossa fracture of distal radius / 中国骨伤

OBJECTIVE@#To explore clinical efficacy of dorsal plate assisted fixation of dorsal lunate fossa fracture block of distal radius.@*METHODS@#From January 2019 to January 2022, 30 patients were treated with dorsal plate assisted fixation of dorsal lunate fossa fracture of distal radius, including 13 males and 17 females, aged from 42 to 68 years old with an average of (48.7±5.6) years old;According to Doi fracture classification, 24 patients were type 3 blocks and 6 patients were type 4 blocks. The degree of palmar angle of anterior and posterior distal radius was fixed by dorsal steel plate during operation. Fracture healing and functional recovery of wrist were observed after operation. Functional evaluation was performed by Gartland and Werley scoring system at 12 months after operation.@*RESULTS@#All patients were followed up from 12 to 13 months with an average of (11.3±0.9) months. All fractures healed for 4 to 5 months with an average of(4.7±0.8) months. Median palpal inclination of anterior and posterior distal radius fixed by dorsal plate was 5.30°(4.85°, 6.03°), 12.45°(11.98°, 13.43°) respectively, and had statistical difference( P<0.01). Gartland and Werley scores was (1.1±0.4) at 12 months afteropertaion, and 27 patients got excellent result and 3 good.@*CONCLUSION@#Dorsal plate assisted fixation of dorsal lunate fossa fractures is beneficial to reduction and stabilization of displaced dorsal fractures and restoration of palmar inclination.

Effects of Qilong Capsules on myocardial fibrosis and insufficient blood circulation in ischemic cardiomyopathy with Qi deficiency and blood stasis / 中国中药杂志

Protective effect of Qilong Capsules(QL) on the myocardial fibrosis and blood circulation of rats with coronary heart disease of Qi deficiency and blood stasis type was investigated. Sleep deprivation and coronary artery ligation were used to construct a disease-symptom combination model, and 60 SD rats were divided into sham operation(sham) group, syndrome(S) group, disease and syndrome(M) group and QL group randomly. The treatment group received administration of QL 0.4 g·kg~(-1)·d~(-1). Other groups were given the same amount of normal saline. The disease indexes of each group [left ventricular end diastolic diameter(LVESD), left ventricular end systolic diameter(LVEDD), left ventricular ejection fraction(LVEF), left ventricular axis shortening rate(LVFS), myocardial histopathology, platelet morphology, peripheral blood flow] and syndrome indexes(tongue color, pulse, grip power) were detected. In sham group, cardiomyocytes and myocardial fibers were arranged neatly and densely with clear structures. The tongues' color in sham were light red, and the pulse shape were regular. RGB is a parameter reflected the brightness of the image of the tongue. In the S group, the amplitude and frequency of the animal's pulse increased accompanied by decreasing R,G,B, however, the decreased R,G,B was accompanied by reduced pulse amplitude in M group. And in M group, we observed fuzzy cell morphology, hypertrophied myocytes, disordered arrangement of cardiomyocytes and myocardial fibers, reduced peripheral blood flow and increased collagen volume fraction(CVF). Increased LVESD and LVEDD, and decreased LVEF and LVFS represented cardiac function in S group was significantly lower than that in sham. In QL group, the tongue's color was red and the pulse was smooth. The myocardial fibers of the QL group were arranged neatly and secreted less collagen. It improved the blood circulation in the sole and tail, and reversed the increasing of LVEDD, LVESD and the decreasing of LVEF and LVFS of M group. Platelets in M and S group showed high reactivity, and QL could decrease aggregation risk. In conclusion, Qilong Capsules has an obvious myocardial protective effect on ischemic cardiomyopathy, which may inhibit the degree of myocardial fibrosis and reduce platelet reactivity.