The value of endoscopic duodenal papilloplasty with titanium clip in improving post-operative complications of choledocholithiasis.

OBJECTIVE: To investigate the value of endoscopic duodenal papillary sphincterotomy combined with balloon dilatation in the treatment of duodenal papilloplasty with titanium clip after choledocholithiasis in post-operative complications. MATERIALS AND METHODS: One hundred and twenty-five patients (69 males and 56 females) with a median age of 65 (32-81) years were included. The treatment plan was randomly divided into Group A (n = 59) and Group B (n = 66) according to the random number table. Patients in Group A were treated with endoscopic sphincterotomy (EST) combined with endoscopic papillary large balloon dilation (EPLBD), followed by a titanium clip for duodenal papilloplasty and then indwelling nasobiliary drainage, whereas those in Group B were treated with EST combined EPLBD to remove stones and then indwelling nasobiliary drainage. RESULTS: In patients with choledocholithiasis or with anatomical changes that make stone extraction difficult, this prospective study attempted to perform duodenal papilloplasty with titanium clips after EST and EPLBD lithotripsy to compare and observe post-operative papillary healing, biliary reflux, and complication rates. CONCLUSIONS: The use of endoscopic duodenal papilloplasty with a titanium clip can improve biliary reflux after lithotripsy and reduce the incidence of post-operative cholangitis complications.

OBJETIVO: Investigar el valor de la esfinterotomía papilar duodenal endoscópica combinada con dilatación con balón en el tratamiento de la papiloplastia duodenal con clip de titanio después de coledocolitiasis en complicaciones postoperatorias. MATERIALES Y MÉTODOS: Se incluyeron un total de 125 pacientes (69 hombres y 56 mujeres) con una mediana de edad de 65 (32-81) años. Los pacientes del Grupo A se trataron con esfinterotomía endoscópica (EST) combinada con dilatación papilar endoscópica con balón grande (EPLBD), seguida de clip de titanio para papiloplastia duodenal y luego drenaje nasobiliar permanente, mientras que los del Grupo B se trataron con EPLBD combinado con EST para eliminar cálculos y luego drenaje nasobiliar permanente. RESULTADOS: En pacientes con coledocolitiasis o con cambios anatómicos que dificultan la extracción de cálculos, este estudio prospectivo intentó realizar papiloplastia duodenal con clips de titanio después de litotricia EST y EPLBD para comparar y observar la cicatrización papilar postoperatoria, el reflujo biliar y las tasas de complicaciones. CONCLUSIÓN: El uso de papiloplastia duodenal endoscópica con clips de titanio puede mejorar el reflujo biliar después de la litotricia y reducir la incidencia de complicaciones de colangitis postoperatorias.

The novel HLA allele, HLA-DPB1*05:01:19, identified in a Chinese bone marrow donor by next-generation sequencing.

HLA-DPB1*05:01:19 differs from DPB1*05:01:01 by one nucleotide in codon 62 in exon 2.

Non-Conventional Allogeneic Anti-BCMA Chimeric Antigen Receptor-Based Immune Cell Therapies for Multiple Myeloma Treatment.

MM, characterized by the progressive accumulation of clonal plasma cells in bone marrow, remains a severe medical problem globally. Currently, almost all MM patients who have received standard treatments will eventually relapse. Autologous anti-BCMA CAR-T cells are one of the FDA-approved immunotherapy cell-based products for treating adults with relapsed or refractory (r/r) multiple myeloma. However, this type of CAR-T cell product has several limitations, including high costs, long manufacturing times, and possible manufacturing failure, which significantly hinder its wider application for more patients. In this review, we summarized the current development stage of applying other types of immune cells to bring the anti-BCMA CAR-T therapy from autologous to allogeneic. In general, anti-BCMA CAR gene-edited αß T cells and CAR-Natural Killer (NK) cells are at the forefront, with multiple clinical trials ongoing, while CAR-γδ T cells and CAR-invariant Natural Killer T (iNKT) cells are still in pre-clinical studies. Other immune cells such as macrophages, B cells, and dendritic cells have been mainly developed to target other antigens and have the potential to be used to target BCMA. Nevertheless, additional regulatory requirements might need to be taken into account in developing these non-conventional allogenic anti-BCMA CAR-based cell products.

Clinical value of preferred endoscopic ultrasound-guided antegrade surgery in the treatment of extrahepatic bile duct malignant obstruction.

OBJECTIVES: To explore the clinical value of preferred ultrasound endoscopic guided biliary drainage in patients with extrahepatic biliary obstruction with intrahepatic biliary ectasis. METHODS: A total of 58 patients with malignant obstruction and intrahepatic bile duct expansion, including 32 males, 26 females and median age 65 (58‒81) were selected. A prospective randomized controlled study was randomized into EUS-AG and ERCP-BD, with 28 patients in EUS-AG and 30 in ERCP-BD. The efficacy of the two treatments, operation success rate, operation time, the incidence of complications, hospitalization days, cost, unimpeded stent duration, and survival time were compared. RESULTS: 1) The surgical success rate in group EUS-AG was 100%, and in group, ERCP-BD was 96.67%. There was no statistical difference in surgical success rate in the two groups (p>0.05). 2) Average operating time in EUS-AG was (23.69±11.57) min, and in ERCP-BD was (36.75±17.69) min. The difference between the two groups has statistical significance (p<0.05). 3) The clinical symptoms of successful patients were significantly relieved. Compared with the preoperative procedure, the differences in group levels had statistical significance (p<0.05); TBIL, ALP, WBC and CRP levels, no statistical significance difference in groups (p>0.05). CONCLUSION: EUS-AG operation has short time, low incidence of complications, safe, effective, and can be used as the preferred treatment plan for patients with extrahepatic biliary duct malignant obstruction associated with intrahepatic biliary duct expansion; EUS-AG operation has more unique clinical advantages for patients with altered gastrointestinal anatomy or upper gastrointestinal obstruction.

Clinical value of preferred endoscopic ultrasound-guided antegrade surgery in the treatment of extrahepatic bile duct malignant obstruction

ABSTRACT Objectives: To explore the clinical value of preferred ultrasound endoscopic guided biliary drainage in patients with extrahepatic biliary obstruction with intrahepatic biliary ectasis. Methods: A total of 58 patients with malignant obstruction and intrahepatic bile duct expansion, including 32 males, 26 females and median age 65 (58-81) were selected. A prospective randomized controlled study was randomized into EUS-AG and ERCP-BD, with 28 patients in EUS-AG and 30 in ERCP-BD. The efficacy of the two treatments, operation success rate, operation time, the incidence of complications, hospitalization days, cost, unimpeded stent duration, and survival time were compared. Results: 1) The surgical success rate in group EUS-AG was 100%, and in group, ERCP-BD was 96.67%. There was no statistical difference in surgical success rate in the two groups (p>0.05). 2) Average operating time in EUS-AG was (23.69±11.57) min, and in ERCP-BD was (36.75±17.69) min. The difference between the two groups has statistical significance (p<0.05). 3) The clinical symptoms of successful patients were significantly relieved. Compared with the preoperative procedure, the differences in group levels had statistical significance (p<0.05); TBIL, ALP, WBC and CRP levels, no statistical significance difference in groups (p>0.05). Conclusion: EUS-AG operation has short time, low incidence of complications, safe, effective, and can be used as the preferred treatment plan for patients with extrahepatic biliary duct malignant obstruction associated with intrahepatic biliary duct expansion; EUS-AG operation has more unique clinical advantages for patients with altered gastrointestinal anatomy or upper gastrointestinal obstruction.

Massively parallel sequencing of 165 ancestry-informative SNPs and forensic biogeographical ancestry inference in three southern Chinese Sinitic/Tai-Kadai populations.

Ancestry informative markers (AIMs), which are distributed throughout the human genome, harbor significant allele frequency differences among diverse ethnic groups. The use of sets of AIMs to reconstruct population history and genetic relationships is attracting interest in the forensic community, because biogeographic ancestry information for a casework sample can potentially be predicted and used to guide the investigative process. However, subpopulation ancestry inference within East Asia remains in its infancy due to a lack of population reference data collection and incomplete validation work on newly developed or commercial AIM sets. In the present study, 316 Chinese persons, including 85 Sinitic-speaking Haikou Han, 120 Qiongzhong Hlai and 111 Daozhen Gelao individuals belonging to Tai-Kadai-speaking populations, were analyzed using the Precision ID Ancestry Panel (165 AISNPs). Combined with our previous 165-AISNP data (375 individuals from 6 populations), the 1000 Genomes Project and forensic literature, comprehensive population genetic comparisons and ancestry inference were further performed via ADMIXTURE, TreeMix, PCA, f-statistics and N-J tree. Although several nonpolymorphic loci were identified in the three southern Chinese populations, the forensic parameters of this ancestry inference panel were better than those for the 23 STR-based Huaxia Platinum System, which is suitable for use as a robust tool in forensic individual identification and parentage testing. The results based on the ancestry assignment and admixture proportion evaluation revealed that this panel could be used successfully to assign individuals at a continental scale but also possessed obvious limitations in discriminatory power in intercontinental individuals, especially for European-Asian admixed Uyghurs or in populations lacking reference databases. Population genetic analyses further revealed five continental population clusters and three East Asian-focused population subgroups, which is consistent with linguistic affiliations. Ancestry composition and multiple phylogenetic analysis further demonstrated that the geographically isolated Qiongzhong Hlai harbored a close phylogenetic relationship with Austronesian speakers and possessed a homogenous Tai-Kadai-dominant ancestry, which could be used as the ancestral source proxy in population history reconstruction of Tai-Kadai-speaking populations and as one of the representatives for forensic database establishment. In summary, more population-specific AIM sets focused on East Asian subpopulations, comprehensive algorithms and high-coverage population reference data should be developed and validated in the next step.

Generation of Mesenchymal Stromal Cells with Low Immunogenicity from Human PBMC-Derived ß2 Microglobulin Knockout Induced Pluripotent Stem Cells.

Mesenchymal stromal cells (MSCs) are viewed as immune-privileged cells and have been broadly applied in allogeneic adoptive cell transfer for regenerative medicine or immune-suppressing purpose. However, the surface expression of human leukocyte antigen (HLA) class I molecules on MSCs could still possibly induce the rejection of allogeneic MSCs from the recipients. Here, we disrupted the ß2 microglobulin (B2M) gene in human peripheral blood mononuclear cell-derived induced pluripotent stem cells (iPSCs) with two clustered regulatory interspaced short palindromic repeat (CRISPR)-associated Cas9 endonuclease-based methods. The B2M knockout iPSCs did not express HLA class I molecules but maintained their pluripotency and genome stability. Subsequently, MSCs were derived from the HLA-negative iPSCs (iMSCs). We demonstrated that B2M knockout did not affect iMSC phenotype, multipotency, and immune suppressive characteristics and, most importantly, reduced iMSC immunogenicity to allogeneic peripheral blood mononuclear cells. Thus, B2M knockout iPSCs could serve as unlimited off-the-shelf cell resources in adoptive cell transfer, while the derived iMSCs hold great potential as universal grafts in allogeneic MSC transplantation.

A cyanine-derivative photosensitizer with enhanced photostability for mitochondria-targeted photodynamic therapy.

A cyanine-derivative photosensitizer, CYBF2, was synthesized for photodynamic therapy of cancer. The photosensitizer can be activated by red-light with enhanced photostability compared to traditional cyanine photosensitizers. CYBF2 was able to generate singlet oxygen inside the cell mitochondria, which efficiently resulted in apoptosis of cancer cells.

Successful en bloc endoscopic full-thickness resection of a giant cervical esophageal leiomyoma originating from muscularis propria.

BACKGROUND: Esophageal leiomyomas, the most common benign primary tumors of the esophagus, are esophageal subepithelial lesions treated by surgery traditionally. In recent years, endoscopic submucosal dissection and related endoscopic treatment techniques are adopted by endoscopists to resect gastrointestinal submucosal tumors. But if a giant esophageal leiomyoma approaches the esophagus entrance and originates from the deep layer of muscularis propria, it will be difficult for both endoscopic resection and surgical treatment. Especially, endoscopic resection has a high risk of huge perforation difficult to be sutured. CASE PRESENTATION: A 72-year-old man with dysphagia underwent gastroscopy examination which indicated a large submucous eminence lesion, about 18-24 cm from the incisors. Endoscopic ultrasonography revealed the lesion was hypoechoic and originated from the muscularis propria with a clear boundary. The patient refused invasive surgical resection. Then, an en bloc endoscopic full-thickness resection was performed, which perforation was successfully closed with purse-string sutures using a novel endoloop device through standard single-channel endoscopy. Histopathologic examination showed an esophageal leiomyoma. CONCLUSION: This endoscopic procedure may be an alternative to avoid surgery for the removal of a giant upper esophagus tumor from muscularis propria layer.

Purse-string sutures using novel endoloops and repositionable clips for the closure of large iatrogenic duodenal perforations with single-channel endoscope: a multicenter study.

BACKGROUND: Serious complications due to perforation restrict the development of duodenal endoscopic treatment. The key stage for remediation is the successful endoscopic closure to prevent peritonitis and the need for surgical intervention. This report aimed to present a new simple method for the closure of large iatrogenic duodenal perforations with purse-string sutures using the novel endoloops and repositionable clips through a single-channel endoscope. METHODS: A total of 23 patients with iatrogenic duodenal perforations ≥ 1 cm were retrospectively studied who were presently treated by purse-string sutures using the novel endoloops and the repositionable hemostasis clips with the single-channel endoscope at four institutes. During and after the procedure, a 20-gauge needle was used to relieve the pneumoperitoneum or subcutaneous emphysema. Finally, a gastroduodenal decompression tube was placed. RESULTS: The median maximum diameter of iatrogenic duodenal perforations was 1.65 cm (range 1.0-3.0 cm). Complete endoscopic closure of all 23 perforations was achieved. No patient had severe complications such as peritonitis. The wounds were healed and no obvious duodenal stricture was observed in all cases after 3 months. CONCLUSION: Purse-string sutures using the novel endoloops and repositionable endoclips through single-channel endoscope were feasible, effective and easy methods for the closure of large duodenal iatrogenic perforations.

Large-scale expansion of Vγ9Vδ2 T cells with engineered K562 feeder cells in G-Rex vessels and their use as chimeric antigen receptor-modified effector cells.

Vγ9Vδ2 T cells are a minor subset of lymphocytes in the peripheral blood that has been extensively investigated for their tolerability, safety and anticancer efficacy. A hindrance to the broad application of these cells for adoptive cellular immunotherapy has been attaining clinically appropriate numbers of Vγ9Vδ2 T cells. Furthermore, Vγ9Vδ2 T cells exist at low frequencies among cancer patients. We, therefore, sought to conceive an economical method that allows for a quick and robust large-scale expansion of Vγ9Vδ2 T cells. A two-step protocol was developed, in which peripheral blood mononuclear cells (PBMCs) from healthy donors or cancer patients were activated with Zometa and interleukin (IL)-2, followed by co-culturing with gamma-irradiated, CD64-, CD86- and CD137L-expressing K562 artificial antigen-presenting cells (aAPCs) in the presence of the anti-CD3 antibody OKT3. We optimized the co-culture ratio of K562 aAPCs to immune cells, and migrated this method to a G-Rex cell growth platform to derive clinically relevant cell numbers in a Good Manufacturing Practice (GMP)-compliant manner. We further include a depletion step to selectively remove αß T lymphocytes. The method exhibited high expansion folds and a specific enrichment of Vγ9Vδ2 T cells. Expanded Vγ9Vδ2 T cells displayed an effector memory phenotype with a concomitant down-regulated expression of inhibitory immune checkpoint receptors. Finally, we ascertained the cytotoxic activity of these expanded cells by using nonmodified and chimeric antigen receptor (CAR)-engrafted Vγ9Vδ2 T cells against a panel of solid tumor cells. Overall, we report an efficient approach to generate highly functional Vγ9Vδ2 T cells in massive numbers suitable for clinical application in an allogeneic setting.

Evaluation of post-mortem heart blood culture in a Chinese population.

BACKGROUND: Post-mortem blood cultures have been used in a wide variety of research studies. However, their significance is still a matter of dispute among medico-legal experts. This study was aimed to determine the factors which influenced post-mortem blood culture results and to assess their value in determining the cause of death. METHODS: We retrospectively investigated 76 post-mortem cases with suspected infection and correlated pathological findings with heart blood culture results. RESULTS: We found that survival time after onset of illness was significantly associated with positive heart blood cultures (P=0.014). Blood culture results were not influenced by age, gender, prior antibiotic therapy, interval time from death to store or interval time from death to autopsy (P>0.05). In those who had heart blood cultures taken, 49 cases (64.5%) including four cases with mixed growth, showed positive results, and approximately one-third of blood cultures were sterile. The positive predictive value (PPV) was 77.6% (38/49) including two cases with mixed growth; most were genuine pathogens according to the clinical and pathological findings. However, the negative predictive value (NPV) was 59.3% (16/27). Escherichia coli, Streptococcus spp., Staphylococcus aureus, Streptococcus pneumoniae and Klebsiella spp. were isolated most often. CONCLUSION: These findings suggest that the results of post-mortem heart blood cultures, when combined with clinical and pathological findings, strengthen the understanding of the cause of death.

Efficacy of antitumor necrosis factor(α) agents on patients with ankylosing spondylitis.

OBJECTIVES: This study was designed to investigate the efficacy of antitumor necrosis factor(TNF)(a) agents (etanercept, infliximab, golimumab or adalimumab) in ankylosing spondylitis (AS). METHODS: A literature search was done using PubMed, Embaseand Cochrane databases. The reference section of all primary studies was inspected for additional references, and only those reporting the results of a randomized-controlled trial comparing etanercept, infliximab or adalimumab with placebo for patients with AS were included in this analysis. RESULTS: Eleven trials with 1851 patients were included. Compared with placebo, anti-TNF(α) agents was associated with significantly higher rates of Assessment in Ankylosing Spondylitis (ASAS) 20 responders (risk ratio [RR]: 2.45, 95% confidence interval [CI]: 2.13-2.82; P < 0.00001), ASAS 50 responders (RR: 3.77, 95% CI: 2.87-4.95; P < 0.00001), ASAS 70 responders (RR: 3.25, 95% CI: 1.97-5.35; P < 0.00001) and patients with partial remission (RR: 5.39, 95% CI: 3.25-8.93; P < 0.00001). In addition, there were more patients with at least 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index score in the experimental groups (RR: 3.07, 95% CI: 2.44-3.86; P < 0.00001). Most adverse events in both treatment groups were mild or moderate in severity. CONCLUSIONS: Anti-TNF(a) agents is an effective and well-tolerated treatment for reducing clinical symptoms of AS.