Clinical management strategies for recipients with renal graft loss / 器官移植

With the maturity of kidney transplantation, introduction of new immunosuppressive drugs and improvement of immunosuppressive regimen, the short-term survival rate of kidney transplant recipients has been significantly improved, whereas the long-term survival rate has not been significantly elevated. Kidney transplant recipients may have the risk of renal graft loss. Clinical management after renal graft loss is complicated, including the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy. These management procedures directly affect clinical prognosis of patients with renal graft loss. Nevertheless, relevant guidelines or consensuses are still lacking. Clinical management of patients after renal graft loss highly depend upon clinicians’ experience. In this article, the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy were reviewed, aiming to provide reference for prolonging the survival and improving the quality of life of these patients.

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

α-Hederin Regulates SREBP1/FASN Pathway and Inhibits Malignant Phenotype of Non-small Cell Lung Cancer / 肿瘤防治研究

Objective To explore the regulative effect of α-Hederin on the proliferation and invasion of NSCLC and investigate its related molecular mechanism. Methods After A549 and HCC-1833 cells were treated with a concentration gradient of α-Hederin for 24 and 48 h, the OD450nm was detected by using CCK8 assays, and the IC50 was calculated.The A549 and HCC-1833 cells were divided into the blank control and α-Hederin groups in accordance with IC50 values.Cell proliferation was detected by EdU assays, and cell cycle transformation and cell apoptosis were detected by flow cytometry.Cell mobility was detected by using Transwell and scratch assays.SREBP1 and FASN protein expression levels were detected through Western blot analysis, and cell lipid accumulation was detected via oil red O staining. Results The survival rate of lung cancer cells decreased significantly with the increase of α-Hederin concentration, and the IC50 values of A549 and HCC-1833 cells at 48 h were 15 and 25 μg/ml, respectively.Compared with the blank control group, cells proliferation and migration were significantly inhibited, cells were blocked in the G1/S phase, the apoptosis rate increased, and the protein expression and lipid accumulation of SREBP1/FASN significantly reduced after α-Hederin treatment. Conclusion α-Hederin can inhibit the proliferation and migration, G1/S phase transition and induce the apoptosis of NSCLC cells and hinder the malignant progression of NSCLC by downregulating the expression of SREBP1 and FASN and reducing the accumulation of cell lipids.

Advances in the diagnosis and treatment of gallbladder carcinoma / 临床肝胆病杂志

Gallbladder carcinoma is a common malignant tumor of the biliary system characterized by poor specificity of early symptoms， a high degree of malignancy， and rapid progression， and it is difficult to make an early diagnosis. Gallstones and gallbladder polyps are considered the most common risk factors for gallbladder carcinoma. Ultrasound is the preferred examination， while CT， MRI， and PET also have their own advantages. There is a lack of radical treatment methods for gallbladder carcinoma， and surgical operation remains the preferred treatment method for gallbladder carcinoma； however， due to the rapid progression of this disease， most patients have lost the opportunity for surgery at the time of diagnosis. A combination of various treatment modalities， such as radiochemotherapy， targeted therapy， and immunotherapy， has improved the prognosis of patients to a certain extent， but with an unsatisfactory long-term therapeutic effect. Therefore， it is of particular importance to give priority to prevention rather than treatment and emphasize early identification and treatment.

Establishment and evaluation of a predictive model for clinical remission of advanced esophageal squamous cell carcinoma after neoadjuvant chemotherapy / 中国胸心血管外科临床杂志

@#Objective     To investigate the influencing factors for the clinical remission of advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemotherapy, establish an individualized nomogram model to predict the clinical remission of advanced ESCC with neoadjuvant chemotherapy and evaluate its efficacy, providing serve for the preoperative adjuvant treatment of ESCC. Methods     The clinical data of patients with esophageal cancer who underwent neoadjuvant chemotherapy (nedaplatin 80 mg/m2, day 3+docetaxel 75 mg/m2, day 1, 2 cycles, 21 days per cycle interval) in the Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College from February 2016 to August 2020 were analyzed retrospectively. According to the WHO criteria for efficacy assessment of solid tumors, tumors were divided into complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD). CR and PR were defined as effective neoadjuvant chemotherapy, and SD and PD were defined as ineffective neoadjuvant chemotherapy. Univariate and multivariate analyses were used to analyze the influencing factors for the short-term efficacy of neoadjuvant chemotherapy. The R software was used to establish a nomogram model for predicting of the model. C-index, calibration curve and receiver operating characteristic (ROC) curve were used to evaluate the predictive performance of the nomogram. Results     Finally 115 patients were enrolled, including 93 males and 22 females, aged 40-75 (64.0±8.0) years. After receiving docetaxel+nedaplatin neoadjuvant chemotherapy for 2 cycles, there were 9 patients with CR, 56 patients with PR, 43 patients with SD and 7 patients with PD. Among them, chemotherapy was effective (CR+PR) in 65 patients and ineffective (SD+PD) in 50 patients, with the clinical effective rate of about 56.5%(65/115). Univariate analysis showed that there were statistical differences in smoking history, alcoholism history, tumor location, tumor differentiation degree, and cN stage before chemotherapy between the effective neoadjuvant chemotherapy group and the ineffective neoadjuvant chemotherapy group (P<0.05). Logistic regression analysis showed that low-differentiation advanced ESCC had the worst clinical response to neoadjuvant chemotherapy, moderately-highly differentiated ESCC responded better (P<0.05). Stage cN0 advanced ESCC responded better to neoadjuvant chemotherapy than stage cN1 and cN2 (P<0.05). The C-index and the area under the ROC curve of the nomogram were both 0.763 (95%CI 0.676-0.850), the calibration curve fit well, the best critical value of the nomogram calculated by the Youden index was 70.04 points, and the sensitivity and specificity of the critical value were 80.0% and 58.0%, respectively. Conclusion    The established clinical prediction model has good discrimination and accuracy, and can provide a reference for individualized analysis of the clinical remission of advanced ESCC with neoadjuvant chemotherapy and the screening of new adjuvant treatment subjects.

A case report of bilateral chylous hemothorax presenting after laparoscopic renal pedicle lymphatic disconnection / 中华泌尿外科杂志

Laparoscopic renal pedicle lymphatic disconnection is the most effective method for treating chyluria that has failed to respond to conservative management. Chylous hemothorax is a rare clinical occurrence resulting from the anatomic abnormality. This paper reported a case, who was admitted with painless gross hematuria for 1 month and was diagnosed with left chylous hematuria. Laparoscopic left renal pedicle lymphatic disconnection was performed, and bilateral chylous hemothorax occurred after the operation. After conservative treatment such as bilateral closed thoracic drainage and blood transfusion support, the patient recovered well. After 2 months of follow-up, there was no obvious effusion in the bilateral thoracic cavity, and the chylous test of urine fluid was negative.

Prognostic factors of spontaneous rupture hemorrhage in primary liver cancer / 中华肝胆外科杂志

Objective:To explore the independent influencing factors of patients with spontaneous rupture hemorrhage of primary liver cancer (PLC).Methods:A retrospective cohort study was conducted. The clinical data of 128 patients with PLC spontaneous rupture hemorrhage in Ningxia Medical University General Hospital from January 2017 to March 2022 were analyzed, including 108 males and 20 females, aged (53.4±10.6) years. According to different treatment, 128 patients were divided into liver resection group (LR, n=28), interventional group [ n=39, transcatheter arterial chemoembolization (TACE) and transcatheter arterial embolization (TAE)], and conservative group ( n=61). Univariate and multivariate Cox regression was performed to analyze prognostic factors. The LR and TACE groups were subdivided into LR (aLR, n=15), TACE/TAE (aTACE, n=33) and LR+ TACE ( n=19) groups. Kaplan-Meier analysis was performed, and the survival rate was compared by log-rank test. Results:The median survival time of LR group and TACE group was 23 months and 21 months, respectively, with no statistical significance ( P>0.05). The median survival time (38 months) in LR+ TACE group was significantly longer than that in aLR group (10 months) and aTACE group (9 months), and the difference was statistically significant ( P<0.05). Univariate analysis showed that Barcelona Clinical Liver Cancer (BCLC)staging, tumor length ≥10.0 cm, vascular invasion, α-fetoprotein ≥400 μg/L, total bilirubin, prothrombin time and treatment affected overall survival of PLC spontaneous rupture hemorrhage patients (all P<0.05). Multivariate analysis showed that BCLC staging, tumor length ≥10.0 cm, Child-Pugh grade and treatment were independent influencing factors for overall survival of PLC spontaneous rupture hemorrhage patients (all P<0.05). Conclusion:BCLC stage, tumor length ≥10.0 cm, Child-Pugh grade and treatment method are independent predictors of overall survival in patients with spontaneous rupture of PLC. LR combined with TACE therapy can improve the survival and prognosis of patients with spontaneous rupture of primary liver cancer.

Rapid health technology assessment of linaclotide in the treatment of constipated irritable bowel syndrome / 中国药房

OBJECTIVE To comprehensively evaluate the effectiveness， safety and economics of linaclotide in the treatment of constipated irritable bowel syndrome （IBS-C）， and to provide the evidence-based basis for clinical application. METHODS Rapid health technology assessment method was adopted； PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang data， VIP database， SinoMed， and related HTA websites were searched. Systematic review/meta-analysis， HTA reports and pharmacoeconomic research about linaclotide were collected. After literature screening， data extraction and quality evaluation， descriptive analysis was used to classify and summarize the research results. RESULTS A total of 11 literature were included， involving 7 systematic reviews/meta-analyses and 4 pharmacoeconomic research. In terms of effectiveness， compared with placebo， linaclotide could achieve FDA specified endpoint and European Medicines Agency-recommended endpoint faster， significantly improved patients’ complete spontaneous bowel movements （CSBM）， abdominal pain， constipation and quality of life， and relieved patients’ global symptoms； compared with the indirect evidence of lubiprostone， plecanatide and tenapanor， the efficacy of linaclotide at the FDA specified endpoint， CSBM， abdominal pain relief， and global relief response were the best. In terms of safety， the incidence of overall adverse drug reactions， diarrhea and flatulence caused by linaclotide were significantly higher than placebo，but patients can tolerate them. In terms of economics， compared with traditional therapeutic drugs， linaclotide showed an economic advantage. CONCLUSIONS Linaclotide has advantages in efficacy， safety and economics in the treatment of IBS-C. It is an effective strategy for the treatment of IBS-C.

Effects of individualized parenteral nutrition versus pre-mixed parenteral nutrition on liver function of patients with acute kidney injury / 中国药房

OBJECTIVE To compare the effects of individualized parenteral nutrition versus pre-mixed parenteral nutrition on liver function of patients with acute kidney injury （AKI）. METHODS Totally 97 AKI patients in the intensive care unit of our hospital from January 2021 to March 2022 were collected and randomly divided into pre-mixed multi-chamber bag （MCB） group （48 cases） and compounded parenteral nutrition （COM） group （49 cases）. The patients in both groups were given routine treatment to correct the reversible cause in time， and parenteral nutrition support treatment was started within 48 hours after the fluid resuscitation was successful or the hemodynamics of low-dose vasoactive drugs were stable. MCB group was given one bag of Fat emulsion amino acid （17） glucose （11%） injection， intravenous infusion， once a day； COM group was given Medium/long chain Fat emulsion injection （C8-24Ve） 0.5-0.8 g/kg+Compound amino acid 18AA-Ⅶ 1.0-1.2 g/kg+Glucose injection 1.5-2.5 g/kg+one Water soluble vitamin injection+Fat-soluble vitamin injection （Ⅱ） 10 mL+Multiple trace element injection （Ⅱ） 10 mL+ individualized supplement of sodium chloride and potassium chloride， with a ratio of glucose to lipid of 5∶5 and a ratio of heat to nitrogen of 100∶1. The treatment course of both groups lasted for 7 days. The percentage of abnormal liver function， the levels of liver function indexes [alanine aminotransferase （ALT）， total bilirubin （TBIL）， aspartate transaminase （AST）]， albumin （ALB）， interleukin-6 （IL-6） and C-reactive protein （CRP） were observed in 2 groups before and after treatment. RESULTS After treatment， the ratio of liver dysfunction， the levels of ALT， AST and CRP in MCB group were significantly higher than before treatment； the ratio of liver dysfunction， the levels of ALT and CRP in MCB group were significantly higher than COM group （P＜0.05）. There were no statistical significance in the ratio of liver dysfunction， the levels of ALT， AST， TBIL and CRP in COM group before and after treatment （P＞0.05）. CONCLUSIONS Individualized parenteral nutrition support treatment can reduce the occurrence of liver injury and improve the nutritional status of AKI patients.

Astragali Radix-Curcumae Rhizoma combination inhibits proliferation, migration, and invasion of colon cancer HT-29 cells by regulating EMT / 中国中药杂志

This study aims to investigate the effect of Astragali Radix-Curcumae Rhizoma(AC) combination on the proliferation, migration, and invasion of colon cancer HT-29 cells based on epithelial-mesenchymal transition(EMT). HT-29 cells were respectively treated with 0, 3, 6 and 12 g·kg~(-1) AC-containing serum for 48 h. The survival and growth of cells were measured by thiazole blue(MTT) colorimetry, and the proliferation, migration, and invasion of cells were detected by 5-ethynyl-2'-deoxyuridine(EdU) test and Transwell assay. Cell apoptosis was examined by flow cytometry. The BALB/c nude mouse model of subcutaneous colon cancer xenograft was established, and then model mice were classified into blank control group, 6 g·kg~(-1) AC group, and 12 g·kg~(-1) AC group. The tumor weight and volume of mice were recorded, and the histopathological morphology of the tumor was observed based on hematoxylin-eosin(HE) staining. The expression of apoptosis-associated proteins B-cell lymphoma-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), and cleaved caspase-3, and EMT-associated proteins E-cadherin, MMP9, MMP2 and vimentin in HT-29 cells and mouse tumor tissues after the treatment of AC was determined by Western blot. The results showed that cell survival rate and the number of cells at proliferation stage decreased compared with those in the blank control group. The number of migrating and invading cells reduced and the number of apoptotic cells increased in the administration groups compared with those in the blank control group. As for the in vivo experiment, compared with the blank control group, the administration groups had small tumors with low mass and shrinkage of cells and karyopycnosis in the tumor tissue, indicating that the AC combination may improve EMT. In addition, the expression of Bcl2 and E-cadherin increased and the expression of Bax, caspase-3, cleaved caspase-3, MMP9, MMP2, and vimentin decreased in HT-29 cells and tumor tissues in each administration group. In summary, the AC combination can significantly inhibit the proliferation, invasion, migration, and EMT of HT-29 cells in vivo and in vitro and promote the apoptosis of colon cancer cells.

Chronic Injury of Mice Bone Marrow Multipotent Hematopoietic Progenitor Cells Induced by Ionizing Radiation / 中国实验血液学杂志

OBJECTIVE@#To explore the chronic injury and its possible mechanism of ionizing radiation on multipotent hematopoietic progenitor cells (MPPs) by determining the related indicators of MPPs in bone marrow of mice post-radiation.@*METHODS@#Sixteen C57BL/6 adult mice were randomly divided into normal control and irradiation groups, 8 mice in each group. The mice in irradiation group were exposed to 6 Gy X-ray. The proportion of bone marrow MPPs, their apoptosis and proliferation 2 months after irradiation were detected by flow cytometry. Mitochondrial activity and levels of reactive oxygen species (ROS) in each MPPs population were detected by Mitotracker Red and DCFDA probes, and the senescent state of MPPs in the bone marrow was analyzed.@*RESULTS@#Ionizing radiation could reduce the proportion of MPPs in mouse bone marrow. The proportions and numbers of MPP1, MPP3 and MPP4 in the bone marrow were significantly decreased after whole-body irradiation with 6 Gy X-ray (P<0.05). In addition, radiation significantly reduced the colony-forming capacity of MPPs in bone marrow (P<0.05), the proportions of apoptotic cells in the MPP1 and MPP4 cell populations increased significantly in the bone marrow (P<0.05). The activity of mitochondria was significantly reduced in the bone marrow MPP2, MPP3 and MPP4 cell populations compared with that of the control group (P<0.05). It was also found that the radiation could significantly increase the ROS levels of MPPs in bone marrow, and the content of ROS in the MPP2, MPP3 and MPP4 cell population of the bone marrow was significantly increased(P<0.05). The senescent cells ratios of MPP1, MPP3 and MPP4 cells in the bone marrow after irradiation were significantly higher than those in the control group (P<0.05).@*CONCLUSION@#Ionizing radiation can cause chronic MPPs damage in mice, which is closely associated with persistent oxidative stress, cells apoptosis, and cellular senescence.

Structural Analysis and Characterization of 4-F-α-PVP Analog 4-F-3-Methyl-α- PVP Hydrochloride / 法医学杂志

OBJECTIVES@#To identify 1-(4-fluorophenyl)-2-(1-pyrrolidinyl) pentan-1-one (4-F-α-PVP) analog 1-(4-fluoro-3-methyl phenyl)-2-(1-pyrrolidinyl) pentan-1-one (4-F-3-Methyl-α-PVP) hydrochloride without reference substance.@*METHODS@#The direct-injection electron ionization-mass spectrometry (EI-MS), GC-MS, electrospray ionization-high resolution mass spectrometry (ESI-HRMS), ultra-high performance liquid chromatography-high resolution tandem mass spectrometry (UPLC-HRMS/MS), nuclear magnetic resonance (NMR), ion chromatography and Fourier transform infrared spectroscopy (FTIR) were integrated utilized to achieve the structural analysis and characterization of the unknown compound in the sample, and the cleavage mechanism of the fragment ions was deduced by EI-MS and UPLC-HRMS/MS.@*RESULTS@#By analyzing the direct-injection EI-MS, GC-MS, ESI-HRMS and UPLC-HRMS/MS of the compound in the samples, it was concluded that the unknown compound was a structural analog of 4-F-α-PVP, possibly with one more methyl group in the benzene ring. According to the analysis results of 1H-NMR and 13C-NMR, it was further proved that the methyl group is located at the 3-position of the benzene ring. Since the actual number of hydrogen in 1H-NMR analysis was one more than 4-F-3-Methyl-α-PVP neutral molecule, it was inferred that the compound existed in the form of salt. Ion chromatography analysis results showed that the compound contained chlorine anion (content 11.14%-11.16%), with the structural analysis of main functional group information by FTIR, the unknown compound was finally determined to be 4-F-3-Methyl-α-PVP hydrochloride.@*CONCLUSIONS@#A comprehensive method using EI-MS, GC-MS, ESI-HRMS, UPLC-HRMS/MS, NMR, ion chromatography and FTIR to identify 4-F-3-Methyl-α-PVP hydrochloride in samples is established, which will be helpful for the forensic science laboratory to identify this compound or other analog compounds.

History and present situation of seromuscular flap anastomosis in proximal gastrectomy / 中华胃肠外科杂志

With the increasing detection rate of early upper gastric cancer and adenocarcinoma of esophagogastric junction, the safety of proximal gastrectomy with clear indications has been verified, and function-preserving proximal gastrectomy has been widely used. However, proximal gastrectomy destructs the normal anatomical structure of esophagogastric junction, resulting in severe postoperative gastroesophageal reflux symptoms and seriously affecting the quality of life. Among various anti-reflux surgery methods, reconstruction of "cardiac valve" has always been the focus of relevant scholars because its similarity with the mechanism of normal anti-reflux. After years of development, evolution and optimization, the designed seromuscular flap anastomosis includes tunnel muscle flap anastomosis, Hatafuku valvuloplasty, single muscle flap anastomosis and double muscle flap anastomosis. The double muscle flap anastomosis has become a research hotspot because it shows good anti-reflux effect in clinical application. This paper reviews the history, research status and hot issues of seromuscular flap anastomosis of esophageal remnant stomach at home and abroad.

Spatial-temporal clustering analysis of hand, foot and mouth disease in Hunan Province in 2016 - 2020 / 公共卫生与预防医学

Objective To analyze the spatial and temporal characteristics of hand, foot and mouth disease (HFMD) in Hunan Province from 2016 to 2020. Methods The data of HFMD in Hunan Province from 2016 to 2020 were collected from China's Disease Prevention and Control Information System. HFMD spatial autocorrelation analysis was conducted by ArcGIS 10.2 software at county level, and spatial-temporal scan statistical analysis was performed by SaTScan 9.7 software. Results A total of 714 157 cases was reported in Hunan Province during 2016-2020, with an average annual incidence rate of 208.36/100 000. Global spatial autocorrelation showed that HFMD had a positive spatial correlation on the county scale in Hunan Province during this period. Local spatial autocorrelation indicated that the hot spots were mainly concentrated in the north of central Hunan, the east of central Hunan and the west of Hunan. Spatial-temporal scanning analysis revealed the first class clusters (RR = 6.65, P< 0.001) covering 34 counties in northern and central Hunan, mainly distributed in Yueyang City, Changsha City, Zhuzhou City, Yiyang City and Xiangtan City from May 2018 to June, and the second class clusters (RR = 3.02, P < 0.001) covering 40 counties in western Hunan and central and southwest Hunan from April 2016 to June 2016. Conclusion HFMD incidence exhibits seasonal and regional characteristics in Hunan Province. The prevention and control of HFMD should be guided by combining the characteristics of spatial-temporal clustering.

Research on the Construction of Hospital Equipment Management Information Platform / 中国医疗器械杂志

With the deepening of China's medical reform, the scale of hospital equipment assets at all levels is also expanding. In the face of large-scale and various equipment assets, the traditional single machine statistical management method not only has a single interface, poor data accuracy and is not compatible with other systems, but also is difficult to achieve "full life cycle" management. In order to solve above problems, the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University of Medicine aims to use the Internet of Things to build a medical equipment management information platform, realize the whole hospital area, whole subject and whole process management of medical materials, and achieve the objectives of business linkage, information connectivity and data sharing between management departments and clinical departments.

Realization and Clinical Study of Robotic Technology in Cardiovascular Interventional Surgery / 中国医疗器械杂志

The high incidence of cardiovascular diseases is a serious threat to human health, and endovascular surgery has become the standard treatment for most interventional cardiovascular diseases. The robotassisted endovascular surgery system further enhances surgeons' ability to perform minimally invasive endovascular procedures in interventional cardiology. This study presents a new robotic technique for coronary intervention from the perspective of clinical application. Aiming at clinical application scenarios, this scheme proposed an intuitive guide wire catheter mechanism design, which accurately and perfectly simulates the doctor's hand movements, realizes the positive and negative direction translation of the guide wire catheter, accurate torque control of the guide wire rotation and locking. The results of animal test showed that the R-OneTM has a high degree of dexterity, accuracy and stability,and meets the clinical needs.

Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Clinical and imaging features of neuroglial heterotopia in children / 中华放射学杂志

Objective:To summarize the clinical and imaging features of pediatric neuroglial heterotopia (NGH) in different locations.Methods:The clinical and preoperative imaging data of 9 patients (6 boys and 3 girls, median age 3 months, range from 1 to13 months) with NGH confirmed by pathology were retrospectively reviewed in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology from October 2009 to December 2020. All patients underwent preoperative CT or/and MR examination. Follow-up was performed in 12 to 60 months after operation, with a median follow-up time of 24 months. The location, range, size, density/signal intensity of the lesions were reviewed.Results:Of all 9 cases, three cases were located in nose (2 extranasal type and 1 mixed type), with the maximum diameter of 13, 13 and 15 mm; there were 3 lesions in tongue, all of which were located on the dorsum of tongue, with the maximum diameter of 13, 18 and 23 mm; there were also 2 cases located in nasopharynx, maximum diameter of 15 and 22 mm, respectively. One case was in sacrococcygeal area, with the maximum diameter as 18 mm. All lesions presented as solid masses with well-defined margins, displaying slightly low density compared to grey matter. The CT value ranged from 25 to 47 HU. Compared to grey matter or spinal cord, MRI demonstrated isointense or slight hypointense on T 1WI and slight hyperintense on T 2WI. All masses presented homogenous density or signal intensity, with mild homogenous enhancement. During postoperative follow-up, no recurrence was found in 8 cases. One case of nasal NGH with gradeⅡcleft lip recurred at 1 month follow-up after surgery, and no recurrence was found after the second surgery. Conclusions:The NGH in children has typical imaging features, and is mostly located at the extracranial midline structure.It presents as solid mass, with quasi-circular morphology, well-defined margins and homogeneous density or signal intensity similar to gray matter or spinal cord. The postoperative recurrence rate is low.

A cyclodextrin-based nanoformulation achieves co-delivery of ginsenoside Rg3 and quercetin for chemo-immunotherapy in colorectal cancer

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

The effect of PAD class on improving the practical ability of dermatovenereology residents / 中华医学教育探索杂志

Objective:To study the effect of PAD (presentation-assimilation-discussion) class applied in the standardized residency training of dermatovenereology on improving residents' practical operation ability.Methods:A total of 120 residents taking the standardized residency training of dermatovenereology in the Affiliated Hospital of North Sichuan Medical College from November 2018 to December 2020 were selected as the research objects and divided into two groups according to the time order of admission, among which, 60 residents enrolled from November 2018 to November 2019 were selected as the control group, and 60 residents enrolled from December 2019 to December 2020 were selected as the experimental group. The control group adopted the traditional standardized residency training mode, and the experimental group adopted the teaching mode of PAD class. SPSS 22.0 statistical software was used for data analysis. The results of theoretical knowledge assessment and skill operation assessment were compared between the two groups by t test, the evaluation of teaching effect was compared between the two groups by chi-square test, and the satisfaction of teaching was compared between the two groups by rank sum test. Results:The theoretical knowledge [(45.38±4.14) points], skill operation [(42.35±4.32) points] and total score [(88.74± 7.69) points] of the experimental group were higher than those of the control group [(39.62 ± 4.15) points, (36.25±4.27) points, (77.96±7.52) points, respectively], with statistical significance ( P<0.05). The evaluation of teaching effect in the experimental group showed that 49 residents (81.67%) believed that their learning interest had been stimulated; 51(85.00%) improved their self-learning ability; 47(78.33%)improved their ability of analyzing and solving problems; 50(83.33%) improved their doctor-patient communication ability; 49(81.67%) improved their clinical thinking ability; 52(86.67%) improved their teamwork ability; and 50(83.33%) improved their literature retrieval ability. The results of satisfaction showed that the experimental group was significantly higher than the control group in sense of responsibility, teaching methods, teaching contents and self-evaluation. Conclusion:The application of PAD class in the standardized residency training of dermatovenereology plays a positive role in mobilizing the learning enthusiasm of residents and cultivating their independent learning ability, and can significantly improve the practical operation and theoretical awareness of residents.