Objective:To prepare heparin (Hep)-modified gelatin methacryloyl (GelMA) microspheres and to investigate their application in liver-targeted delivery of adipose-derived mesenchymal stem cells (ADSCs).Methods:GelMA microspheres were modified with Hep to obtain GelMA-Hep microspheres. The surface morphology of the GelMA-Hep microspheres was observed by scanning electron microscopy. The changes of carbon atoms, nitrogen atoms and sulfur atoms on the surface of the GelMA-Hep microspheres were detected by X-ray photoelectron spectroscopy. The surface chemical group composition of the GelMA-Hep microspheres was analyzed by Fourier transform infrared spectrometer. The swelling properties of the GelMA-Hep microspheres were detected by water absorption swelling experiment. Human liver HL-7702 cells transfected with lentivirus were co-cultured with GelMA, GelMA-dopamine (GelMA-dop) and GelMA-Hep microspheres. The effects of microspheres on cell proliferation activity were evaluated by cell counting kit-8 method and live/dead cell staining experiment. The adhesion of microspheres to cells was observed by confocal microscopy. The GelMA-Hep microspheres loaded with ADSCs were injected into C57BL/6 mice through the tail vein, and its efficiency of liver-targeted delivery of ADSCs was observed by a small animal in vivo imaging system. The data were compared by independent sample t test or one-way analysis of variance. Results:The GelMA-Hep microspheres were prepared by modifying the GelMA microspheres with Hep. Compared with the GelMA microspheres, the size of the GelMA-Hep microspheres did not change significantly, and the surface did not collapse and showed some crystalline particles. The binding energy of sulfur atoms on the surface of the GelMA-Hep microspheres increased from 166 eV to 168 eV. On the surface of the GelMA-Hep microspheres, the characteristic peaks of sulfonic acid and sulfate groups of Hep were detected at 1 490 cm ?1 and from 1 135 cm ?1 to 1 050 cm ?1, respectively. The swelling rate of the GelMA-dop microspheres was uniform, while the swelling rate of the GelMA microspheres and the GelMA-Hep microsphere was quite different, but the final swelling mass of the three microspheres tended to be consistent at 5 min. After 12, 24, 36 and 48 h of culture, the relative proliferation of cells in the GelMA-Hep group (1.61±0.29, 1.78±0.05, 2.27±0.08, 2.26±0.33) were higher than those in the negative control group (1.00±0.00, 1.28±0.06, 1.39±0.02, 1.41±0.04) (all P<0.05). After 36 h of culture, the relative proliferation of cells in the GelMA-Hep group was higher than that in the GelMA-dop group (1.63±0.21), with significant difference ( P<0.05). Live/dead cell staining experiment showed that after 12 h of cell culture in the GelMA-Hep group, only a few microspheres had cell adhesion; at 24 h, the cells were densely distributed on the surface of the microspheres. After 36 h, the number of cells increased further. At 48 h, live cells were distributed throughout the microspheres. Confocal microscopy showed that after 24 h of culture, cells adhered to the surface of the microspheres in the GelMA-Hep group and showed a stretched morphology. The liver of the GelMA-Hep+ADSCs group showed strong fluorescence at 0.5 h, and the fluorescence brightness continued to 48.0 h. The number of ADSCs reaching the liver was more than that of ADSCs group and GelMA+ADSCs group. Conclusions:GelMA-Hep microspheres were successfully prepared, which can improve the efficiency of liver-targeted delivery of ADSCs.

There is still a lack of guidelines on biliary cannulation in recent years. The guidelines are an initiative of the World Endoscopy Organization （WEO） formulated by a panel of experts from Asia， Europe， and America. Through a systematic literature review and the application of the Grading of Recommendations Assessment， Development， and Evaluation methodology， the guidelines address clinical questions pertaining to four key domains， i.e.， prevention of post-ERCP pancreatitis （PEP）， bile duct cannulation techniques， sphincterotomy/papillary balloon dilation， and bile duct cannulation under special circumstances. Successful biliary cannulation and sphincterotomy are cornerstones of ERCP and are indispensable for almost all therapeutic and advanced diagnostic procedures； however， adverse events， especially PEP， may occur frequently and affect the prognosis of patients. A high success rate of bile duct cannulation and a low incidence rate of PEP are quality indicators for ERCP and should be the goal of all endoscopists. The guidelines aim to provide clinical practice recommendations applicable worldwide， regardless of resources and expertise. The guidelines cover the preoperative， intraoperative， and postoperative management of ERCP， including the measures to reduce the risk of PEP， the technique for an initial biliary cannulation attempt， options for cannulation in case of difficult biliary access， alternatives to ERCP in case of failure （under the guidance of percutaneous and endoscopic ultrasound）， and biliary access in altered anatomy （periampullary diverticulum and postsurgical anatomy） and in the presence of duodenal stenosis.

The rising prevalence of allergic diseases imposes a significant burden on healthcare resources and socio-economic systems. Allergen testing plays a critical role in the prevention, diagnosis, and treatment of allergic diseases. However, its application in clinical practice still faces numerous challenges. This article reviews the current status of allergen testing in clinical settings and discusses the challenges in managing allergic diseases. Additionally, it provides recommendations for improving medical education on allergen testing and promoting standardized clinical management of allergic diseases.

The rising prevalence of allergic diseases imposes a significant burden on healthcare resources and socio-economic systems. Allergen testing plays a critical role in the prevention, diagnosis, and treatment of allergic diseases. However, its application in clinical practice still faces numerous challenges. This article reviews the current status of allergen testing in clinical settings and discusses the challenges in managing allergic diseases. Additionally, it provides recommendations for improving medical education on allergen testing and promoting standardized clinical management of allergic diseases.

Using constructivism theory， this study explored the relationship between the "origin" and "flow" of academic schools in traditional Chinese medicine （TCM）， clarified the developmental patterns of schools， and provided insights for the modernization， inheritance， and innovation of current schools. Academic schools originate from different cultural sources， and their differentiation and development are similar to the replication， spread and variation of biological "genes". The theoretical characteristics of constructivism align well with the principles of formation and differentiation of academic schools. The construction of academic thoughts and core diagnostic and therapeutic concepts within each school can be seen as a multilevel unity of self-construction， mutual construction among individuals， and social construction. Firstly， individual medical practitioners choose and inherit from the origins of TCM， integrating personalized understanding， which then differentiates into various schools in the history of academia. Secondly， during the process of cultural inheritance， medical practitioners from different times and regions gradually form academic schools and local medical schools through the method of "tailoring strategies to three categories of etiological factors" and mutual construction among individuals. Finally， in the context of the scientific， standardized， and intelligent development of modern medicine， the further evolution of academic schools needs to follow the evolutionary laws of traditional medicine， combine with the health needs of the new era， adopt a social construction approach， facilitate multi-party participation in the inheritance and innovation of academic thoughts and clinical experiences， and utilize the internet and intelligent technology means to empower modern development.

Objective:To analyze the advantages and disadvantages of online and offline laboratory medicine continuing education and training, and to discuss the future continuing education and training mode under new technology development and new situation.Methods:A questionnaire was administered to the trainees who participated in the 2019 and/or 2020 national continuing medical education project—Clinical Application and Evaluation of New Technologies and Methods of Laboratory Medicine—sponsored by the Department of Laboratory Medicine, West China Hospital, Sichuan University. One hundred and twenty-four questionnaires were completed for the 2019 offline training, and 503 questionnaires were completed for the 2020 online training. The rank sum test, Fisher's exact test, and chi-square test were performed for statistical analysis with the use of SPSS 26.0.Results:The participants in 2020 were significantly younger and the proportion of female participants in 2020 was significantly higher compared with those in 2019. Intermediate titles or above accounted for 66.93% (83/124) in 2019, and intermediate titles or below accounted for 88.67% (446/503) in 2020. The proportion of people from Sichuan Province was significantly higher in 2019. The proportion of trainees from primary institutions was significantly lower in 2019. In 2019, public institutions were mainly tertiary hospitals (74.31%, 81/109), and the majority of participants from private institutions were from third party testing institutions (60.00%, 9/15). In 2020, the percentage of tertiary hospitals in public institutions decreased to 60.99% (258/423), while the percentage of community medical institutions increased to 10.64% (45/423), and 75.00% (60/80) of trainees from private institutions were from tertiary and secondary medical institutions. Trainees with lower educational levels were more likely to appreciate the value of the training course, especially with higher degrees of satisfaction with improvements in theoretical levels and practical skills, and participants from primary institutions believed that the training course could effectively improve their theoretical and practical levels. The number of participants who provided suggestions on laboratory medicine continuing education and training needs in 2019 (83.75%, 67/80) was higher than that in 2020 (48.51%, 244/503). The overall pass rate of post-training assessment in 2020 was 88.52% (424/479).Conclusions:Online and offline training modes have different audience groups and training effects. Online continuing education can provide training opportunities to more primary care personnel and junior and intermediate professionals, which is conducive to improving the basic professional literacy and testing skills of laboratory personnel on the whole. At the same time, the integration of online and offline modes will promote the development of laboratory medicine continuing education.

Objective:To investigate the clinical efficacy in one stage reconstruction of composite defects of Achilles tendon and surrounding soft tissues with a flap transfer combined with allogeneic tendon transplantation.Methods:From July 2018 to August 2022, a total of 12 patients, including 9 males and 3 females, with a mean age of 31.5(ranged 8 to 56) years old, had surgery with flap transfer combined with transplantation of allogeneic tendon in one stage reconstruction for compound defects of Achilles tendon and soft tissue at the Department of Orthopaedics of First Affiliated Hospital of Nanchang University. The defects of Achilles tendons ranged from 4.0 to 9.0 cm, and the soft tissue defects sized from 3.0 cm × 4.0 cm to 14.0 cm × 6.0 cm. Of the 12 patients, 6 received transfers of sural neurovascular flaps, 3 with peroneal perforator flaps and 3 with free anterolateral thigh flaps(ALTF). The flaps sized from 4.0 cm × 4.5 cm to 15.0 cm×7.0 cm, and in addition, allogeneic tendon grafts were used to reconstruct the defects of Achilles tendons in all patients. All the flap donor sites were either directly sutured or covered with skin grafts. Follow-up was carried out by visits of outpatient clinic or telephone or WeChat distant interviews. The flap survival and recovery of ankle function and Achilles tendon were observed.Results:During the 3 months to 2 years of follow-up, none of the patient showed obvious immunological rejection against the transplanted allogeneic tendon. All 12 flaps survived well with the colour and texture close to the surrounding skin. No ulceration occurred in both of the donor and recipient sites. There was no re-rupture of the transplanted allogeneic tendon. At the final follow-up, ankle movement was measured at 13.4°±2.6° in dorsal extension and 33.6°±3.2° in plantar flexion. According to American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hind foot function score, a score of 88.7±5.6 was achieved with 7 patients in excellent, 4 in good and 1 was acceptable.Conclusion:In patients with a composite defect of Achilles tendon and surrrounding soft tissue, the application of a flap transfer combined with a homogeneous allograft tendon transplantation in an one stage surgery is a feasible surgical procedure. It can achieve a satisfactory outcome with less trauma and fewer complications.

Objective:To observe the efficacy and safety of radium-223 in metastatic castration resistant prostate cancer (mCRPC) with bone metastasis.Methods:The clinical data of 48 patients with mCRPC treated with radium-223(55 kBq/kg, once every 4 weeks, planned to use for 6 cycles)from February 2021 to May 2022 were analyzed retrospectively. All patients had symptomatic bone metastasis without visceral metastasis, which the number of bone metastasis was more than one site.They were all classified as IVb stage. The average age was 70.5 (ranging 49-90) years. The median PSA was 44.70(ranging 0.15-1 864.00) ng/ml. The median ALP was 162 (ranging 43-1 589) U/L. The median time from mCRPC diagnosis to radium-223 use was 10 (ranging 3-47) months. 9, 18 and 11 patients had received first-line, second-line and third-line treatment for mCRPC before enrollment respectively, 10 patients had received at least fourth-line treatment. 38 (79.1%), 31 (64.5%), 30 (62.5%) and 7 (14.6%) patients had used abiraterone, enzalutamide, docetaxel and olaparib before enrollment. The probability of PSA level decrease >30%, ALP level decrease >30%, symptom improvement rate, median overall survival (OS), as well as the occurrence of treatment-related adverse reactions and the reasons for withdraw treatment were analyzed.Results:The median follow-up time was 8 (ranging 1-16) months. 11 patients completed all 6 courses of treatment. The median number of completed courses was 4 (ranging 1-6). 27 patients (56.2%) received radium-223 and bone protection drugs (Bisphosphate/ Denosumab). PSA decreased by >30% was recorded in 10 patients (20.8%) and ALP decreased by >30% was recorded in 25 patients (52.1%). 23 cases (47.9%) reported bone pain relief during treatment. Among the 9 patients who had received first-line of mCRPC previously, 6 cases (66%) had relief of bone pain symptoms, and 4 cases (44%) had a decrease of PSA >30%. Among the 18 patients who had previously received second-line mCRPC treatment, 11 cases (61%) had relief of bone pain symptoms, and 4 cases (22%) had a decrease of PSA >30%. Among the 21 patients who had received third-line or more mCRPC treatment in the past, 6 (28.5%) had symptom relief, and 2 (9.5%) had PSA decrease >30%. The median overall survival (OS) was not reached, and the OS was estimated to be 12.5 months using the Kaplan-Meier method. The most common hematological adverse effects were thrombocytopenia (15 cases, 31.2%; grade 3 in 6 cases and grade 4 in 0), followed by leucopenia (11 cases, 22.9%; grade 3 in 4 cases and grade 4 in 1 case) and anemia (8 cases, 16.7%; grade 3 in 3 cases and grade 4 in 0). Non-hematological adverse reactions included fever in 1 case (2.1%), constipation in 4 cases (8.3%), nausea and vomiting in 10 cases (20.8%), diarrhea in 7 cases (14.6%), dizziness in 1 case (2.1%) and fatigue in 11 cases (22.9%). Seven cases were discontinued due to intolerable adverse reactions (median 2 courses), 14 cases were discontinued due to disease progression or death (median 2 courses), and 5 cases were discontinued due to other reasons (median 1 course).Conclusions:Radium-223 has a good performance in symptom control for mCRPC patients who have previously received first-line or second-line therapy. Due to the high incidence of hematological adverse reactions, more attention should be paid to the changes of hemogram during the treatment, and timely treatment should be carried out to improve the drug tolerance of patients.

Objective To analyze the clinical features and risk factors of delayed intracranial hemorrhage (DICH) after ventriculoperitoneal shunt (VPS) in patients with communicating hydrocephalus.Methods One hundred and seventy-six patients with ventriculoperitoneal shunt due to communicating hydrocephalus secondary to craniocerebral trauma,hypertensive intracerebral hemorrhage,brain tumor or intracranial aneurysm rupture hemorrhage,admitted to our hospital from January 2012 to August 2018,were selected in our study;these patients were divided into DICH group and non-DICH group according to whether or not DICH occurred.The clinical features,including incidence,time and location of DICH,were analyzed.The differences of age,gender,length of stay,concomitant diseases,previous operation history,incidences of subdural effusion and puncture canal edema after ventriculoperitoneal shunt,and history of down-regulating shunt valve within 2 weeks between the two groups were compared by univariate analysis.The independent risk factors for DICH were further assessed using multivariable Logistic regression.Results Among 176 patients,23 (13.07％) had DICH;2-11 d after surgery,DICH appeared,manifesting as subdural,ventriculoventricular end canal and/or hemorrhage in one or more areas of the ventricle.There were significant differences in incidence of subdural effusion and history of down-regulating shunt valve within 2 weeks between the two groups (P＜0.05).Multivariate Logistic regression analysis showed that subdural effusion after surgery and down-regulation of shunt valve pressure within 2 weeks after ventriculoperitoneal shunt were independent risk factors for DICH (OR=4.516,95％CI:1.555-13.110,P=0.006;OR=5.352,95％CI:1.987-14.414,P=0.001).Conclusion High incidence of DICH mighty be noted within two weeks of ventriculoperitoneal shunt;subdural effusion and pressure reduction of shunt valve within 2 weeks are independent risk factors for DICH,which needs close monitoring and clinical intervention.

Objective To compare the effectiveness and safety of ultramini percutaneous nephrolithotomy (UMP) and retrograde intrarenal surgery (RIRS) in treatment of moderate-sized (about 1-2 cm) renal lower caliceal calculi.Methods From March 2015 to December 2016,patients in our hospital scheduled for surgery due to renal lower caliceal calculi with the greatest diameter of 10-22 mm were prospectively analyzed.Patients were randomized into two groups according to the random number table.Group UMP's operational channel was only F14 and the nephroscope's diameter was 1 mm.200 μm holmium laser lithotripsy was used to break the stones which was rushed out by eddy cuurent.In Group RIRS,all patients needed placing a F6 double J stent preoperatively for two weeks.A flexible ureteroscope sheath required imbedding intraoperatively.The stones were smashed by 200 μm holmium laser lithotripsy through the WOLF flexible ureteroscope.The intraoperative and postoperative datas including stone-free status and the complications were compared.Results 100 patients were enrolled in the study 50 patients in Group UMP,28 were male and 22 were female,mean age was 43.4 ± 7.9 years old.Mean stone size was 14.5 ±3.0 mm(range 10-22 mm).Among them,18 cases were complicated with mild and moderate hydronephrosis.The other 50 cases were allocated to Group RIRS,including 31 males and 19 females.Their mean age was 44.5 ± 8.3 years old and mean stone size was 13.7 ± 3.1 mm (range 10-21 mm).Among them,16 cases were complicated with mild and moderate hydronephrosis.No statistically significant difference were seen between the two groups (P ＞ 0.05).After three months' follow-up,one-time stone free rate(SFR) of UMP group was 94.0％ (47/50),which was significantly more superior than the 72.0％ (36/50) of the RIRS group(P ＜ 0.05).The intraoperative decrease in hemoglobin were (7.8 ± 3.3) g/L vs.(3.1 ± 3.4) g/L,and operating time(26.5 ± 6.1) min vs.(43.3 ± 6.3) min.Significant differences were also seen between the two groups(P ＜0.05).There was more blood loss and less operating time in the group of UMP.The hospital stay,delayed hemorrhage and postoperative fever between the UMP and RIRS groups were (4.3±1.3)d vs.(3.24 ± 1.21)d,8.0％ (4/50)vs.0(0/50),16.0％ (8/50)vs.12.0％ (6/50) respectively.No significant differences were seen (P ＞ 0.05).Conclusions Both UMP and RIRS procedures are effective and safe in the treatment of moderate-sized renal lower caliceal calculi.Compared with RIRS,UMP may be more effective and has less operating time,however wtih more intraoperative blood loss.