The association and underlying mechanism of the digit ratio (2D:4D) in hypospadias.

ABSTRACT: The second-to-fourth digit (2D:4D) ratio is thought to be associated with prenatal androgen exposure. However, the relationship between the 2D:4D ratio and hypospadias is poorly understood, and its molecular mechanism is not clear. In this study, by analyzing the hand digit length of 142 boys with hypospadias (23 distal, 68 middle, and 51 proximal) and 196 controls enrolled in Shanghai Children's Hospital (Shanghai, China) from December 2020 to December 2021, we found that the 2D:4D ratio was significantly increased in boys with hypospadias (P < 0.001) and it was positively correlated with the severity of the hypospadias. This was further verified by the comparison of control mice and prenatal low testosterone mice model obtained by knocking out the risk gene (dynein axonemal heavy chain 8 [DNAH8]) associated with hypospadias. Furthermore, the discrepancy was mainly caused by a shift in 4D. Proteomic characterization of a mouse model validated that low testosterone levels during pregnancy can impair the growth and development of 4D. Comprehensive mechanistic explorations revealed that during the androgen-sensitive window, the downregulation of the androgen receptor (AR) caused by low testosterone levels, as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a (Wnt5a), Wnt5b, Smad family member 2 (Smad2), and Smad3; mitochondrial function-related genes in cartilage such as AMP-activated protein kinase (AMPK) and nuclear respiratory factor 1 (Nrf-1); and vascular development-related genes such as myosin light chain (MLC), notch receptor 3 (Notch3), and sphingosine kinase 1 (Sphk1), are responsible for the limitation of 4D growth, which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral ossification. This study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism.

Influence of different magnetic forces on the effect of colonic anastomosis in rats.

BACKGROUND: Despite much work having been conducted on magnetic compression anastomosis (MCA) in the digestive tract, there are no reports on the influence of magnetic force on the anastomosis. AIM: To investigate the effect of different magnetic force magnets on the MCA of the digestive tract. METHODS: Two groups of magnets of the same sizes but different magnetic forces were designed and produced. A total of 24 Sprague-Dawley rats were randomly assigned into two groups (powerful magnet group and common magnet group), with 12 rats in each group. Two types of magnets were used to complete the colonic side-to-side anastomosis of the rats. The operation time and magnet discharge time were recorded. The anastomotic specimens were obtained 4 wk after the operation and then the burst pressure and diameter of the anastomosis were measured, and the anastomosis was observed via the naked eye and subjected to histological examination. RESULTS: The magnetic forces of the powerful and common magnet groups at zero distance were 8.26 N and 4.10 N, respectively. The colonic side-to-side anastomosis was completed in all 24 rats, and the operation success rate and postoperative survival rate were 100%. No significant difference was noted in the operation time between the two groups. The magnet discharge time of the powerful magnet group was slightly longer than that of the common magnet group, but the difference was not statistically significant (P = 0.513). Furthermore, there was no statistical difference in the burst pressure (P = 0.266) or diameter of magnetic anastomosis (P = 0.095) between the two groups. The gross specimens of the two groups showed good anastomotic healing, and histological observation indicated good mucosal continuity without differences on healing. CONCLUSION: In the rat colonic side-to-side MCA model, both the powerful magnet with 8.26 N and the common magnet with 4.10 N showed no significant impact on the anastomosis establishment process or its effect.

A novel magnetic compression technique for establishment of a vesicovaginal fistula model in Beagle dogs.

Vesicovaginal fistula lacks a standard, established animal model, making surgical innovations for this condition challenging. Herein, we aimed to non-surgically establish vesicovaginal fistula using the magnetic compression technique, and the feasibility of this method was explored using eight female Beagle dogs as model animals. In these dogs, cylindrical daughter and parent magnets were implanted into the bladder and vagina, respectively, after anesthesia, and the positions of these magnets were adjusted under X-ray supervision to make them attract each other, thus forming the structure of daughter magnet-bladder wall-vaginal wall-parent magnet. Operation time and collateral damage were recorded. The experimental animals were euthanized 2 weeks postoperatively, and the vesicovaginal fistula gross specimens were obtained. The size of the fistula was measured. Vesicovaginal fistula was observed by naked eye and under a light microscope. Magnet placement was successful in all dogs, and remained in the established position for the reminder of the experiment. The average operation time was 14.38 min ± 1.66 min (range, 12-17 min). The dogs were generally in good condition postoperatively and were voiding normally, with no complications like bleeding and urine retention. The magnets were removed from the vagina after euthanasia. The vesicovaginal fistula was successfully established according to gross observation, and the fistula diameters were 4.50-6.24 mm. Histological observation revealed that the bladder mucosa and vaginal mucosa were in close contact on the internal surface of the fistula. Taken together, magnetic compression technique is a simple and feasible method to establish an animal model of vesicovaginal fistula using Beagle dogs. This model can help clinicians study new surgical techniques and practice innovative approaches for treating vesicovaginal fistula.

Y-Z deformable magnetic ring for the treatment of rectal stricture: A case report and review of literature.

BACKGROUND: Treatment of postoperative anastomotic stenosis for colorectal cancer is often challenging, especially for patients who do not respond well to endoscopy. In cases where patients have undergone an enterostomy, the stenosis can be easily resolved through magnetic compression. However, common magnetic compression techniques cannot be performed on those without enterostomy. We designed a novel Y-Z deformable magnetic ring (Y-Z DMR) and successfully applied it to a patient with a stenosis rectal anastomosis and without enterostomy after rectal cancer surgery. CASE SUMMARY: We here report the case of a 57-year-old woman who had undergone a laparoscopic radical rectum resection (Dixon) for rectal cancer. However, she started facing difficulty in defecation 6 months after surgery. Her colonoscopy indicated stenosis of the rectal anastomosis. Endoscopic balloon dilation was performed six times on her. However, the stenosis still showed a trend of gradual aggravation. Because the patient did not undergo an enterostomy, the conventional endoscopic magnetic compression technique could not be performed. Hence, we implemented a Y-Z DMR implemented through the anus under single channel. The magnetic ring fell off nine days after the operation and the rectal stenosis was relieved. The patient was followed up for six months and reported good defecation. CONCLUSION: The Y-Z DMR deformable magnetic ring is an excellent treatment strategy for patients with rectal stenosis and without enterostomy.

Sex-determining region Y gene promotes liver fibrosis and accounts for sexual dimorphism in its pathophysiology.

BACKGROUND & AIMS: Men are more prone to develop and die from liver fibrosis than women. In this study, we aim to investigate how sex-determining region Y gene (SRY) in hepatocytes promotes liver fibrosis. METHODS: Hepatocyte-specific Sry knock-in (KI), Sry knockout (KO), and Sry KI with platelet-derived growth factor receptor α (Pdgfrα) KO mice were generated. Liver fibrosis was induced in mice by bile duct ligation for 2 weeks or carbon tetrachloride treatment for 6 weeks. In addition, primary hepatocytes, hepatic stellate cells (HSCs), and immortalized cell lines were used for in vitro studies and mechanistic investigation. RESULTS: Compared to females, the severity of toxin- or cholestasis-induced liver fibrosis is similarly increased in castrated and uncastrated male mice. Among all Y chromosome-encoded genes, SRY was the most significantly upregulated and consistently increased gene in fibrotic/cirrhotic livers in male patients and in mouse models. Sry KI mice developed exacerbated liver fibrosis, whereas Sry KO mice had alleviated liver fibrosis, compared to age- and sex-matched control mice after bile duct ligation or administration of carbon tetrachloride. Mechanistically, both our in vivo and in vitro studies illustrated that SRY in hepatocytes can transcriptionally regulate Pdgfrα expression, and promote HMGB1 (high mobility group box 1) release and subsequent HSC activation. Pdgfrα KO or treatment with the SRY inhibitor DAX1 in Sry KI mice abolished SRY-induced HMGB1 secretion and liver fibrosis. CONCLUSIONS: SRY is a strong pro-fibrotic factor and accounts for the sex disparity observed in liver fibrosis, suggesting its critical role as a potentially sex-specific therapeutic target for prevention and treatment of the disease. IMPACT AND IMPLICATION: We identified that a male-specific gene, sex-determining region Y gene (SRY), is a strong pro-fibrotic gene that accounts for the sex disparity observed in liver fibrosis. As such, SRY might be an appropriate target for surveillance and treatment of liver fibrosis in a sex-specific manner. Additionally, SRY might be a key player in the sexual dimorphism observed in hepatic pathophysiology more generally.

Intracellular Magnetic Hyperthermia Enables Concurrent Down-Regulation of CD47 and SIRPα To Potentiate Antitumor Immunity.

Harnessing the potential of tumor-associated macrophages (TAMs) to engulf tumor cells offers promising avenues for cancer therapy. Targeting phagocytosis checkpoints, particularly the CD47-signal regulatory protein α (SIRPα) axis, is crucial for modulating TAM activity. However, single checkpoint inhibition has shown a limited efficacy. In this study, we demonstrate that ferrimagnetic vortex-domain iron oxide (FVIO) nanoring-mediated magnetic hyperthermia effectively suppresses the expression of CD47 protein on Hepa1-6 tumor cells and SIRPα receptor on macrophages, which disrupts CD47-SIRPα interaction. FVIO-mediated magnetic hyperthermia also induces immunogenic cell death and polarizes TAMs toward M1 phenotype. These changes collectively bolster the phagocytic ability of macrophages to eliminate tumor cells. Furthermore, FVIO-mediated magnetic hyperthermia concurrently escalates cytotoxic T lymphocyte levels and diminishes regulatory T cell levels. Our findings reveal that magnetic hyperthermia offers a novel approach for dual down-regulation of CD47 and SIRPα, reshaping the tumor microenvironment to stimulate immune responses, culminating in significant antitumor activity.

Endoscopic gastrointestinal bypass anastomosis using deformable self-assembled magnetic anastomosis rings (DSAMARs) in a pig model.

BACKGROUND: To investigate the feasibility of a deformable self-assembled magnetic anastomosis ring (DSAMAR), designed and developed by us, for endoscopic gastrointestinal bypass anastomosis. METHODS: Ten experimental pigs were used as model animals. The DSAMAR comprises 10 trapezoidal magnetic units, arranged in a straight line under the constraint of a guide wire. When the desired anastomosis site is reached under the guidance of an endoscope, the catheter pushes the magnetic unit along the guide wire. The linear DSAMAR can be assembled into a circular DSAMAR. Two DSAMARs were inserted, one at the end of the duodenum and the other into the stomach successively. They attracted each other and compressed the wall of the stomach and duodenum to establish gastrointestinal bypass anastomosis. The experimental pigs were euthanized 4 weeks after the operation, and the gastrointestinal bypass anastomosis specimens were obtained. The anastomosis formation was evaluated by the naked eye and histology. RESULTS: Gastrointestinal bypass anastomosis with DSAMARs was successfully performed. The average operation time under an endoscope was 70.30 ± 19.05 min (range: 43-95 min). The DSAMARs were discharged through the anus 10-17 days after surgery. There were no complications such as gastrointestinal bleeding, perforation, anastomotic fistula, and gastrointestinal obstruction during and after the operation. Gastroscopy and gross specimen of the anastomosis showed a well-formed magnetic anastomosis. Histological observation showed good continuity of the serous membrane and the mucosa of magnetic anastomosis. CONCLUSION: The DSAMAR is a safe and feasible device for fashioning gastrointestinal bypass anastomosis in this animal model.

Application of Y-Z deformable magnetic ring for recanalization of transanal single-access rectal stricture.

Magnetic compression anastomosis has been reported to have remarkable clinical outcomes. Here, we tested the applicability of a Y-Z deformable magnetic ring (DMR) for non-surgical manipulation of rectal stenosis (RS) in a beagle dog model under a transanal single-access condition. RS was modeled in 8 beagle dogs using partial ligation with silk thread. Under X-ray guidance, the Y-Z DMR was positioned at the proximal and distal ends of the RS, and the magnetic ring was bent into an "O" shape, such that the two rings were magnetically attracted. Operation time, complications during or after operation, and discharge time of the magnetic rings were recorded. The anastomosis bursting pressure was measured two weeks after removing the rings, and its formation was assessed through gross and histological examination. Partial ligation with a silk thread successfully established the canine RS model. After Y-Z DMR installation, the magnetic ring was successfully reconfigured from an "S" to an "O" shape. Strong attraction existed between the rings. The operation time was 9-15 min (average: 11.75 ± 1.98 min). No rectal bleeding or perforation occurred during or after operation. The ring was naturally expelled 7-10 days after surgery. A pressure of > 300 mmHg was recorded at the point of anastomosis rupture. The rectal anastomosis appeared to have healed properly on the surface, which was confirmed histologically, signifying the success of this procedure. A Y-Z DMR facilitated the successful recanalization of transanal single-channel RS without needing surgery in an animal model.

Appropriate time for ejection fraction reassessment after revascularization in patients with left ventricular dysfunction for risk stratification of sudden cardiac death.

BACKGROUND: Appropriate time for ejection fraction (EF) reassessment after revascularization in patients with left ventricular dysfunction has not been investigated comprehensively, although 3 months after revascularization is recommended to stratify the risk of sudden cardiac death (SCD). HYPOTHESIS: EF reassessed within different timeframe after revascularization may have incosistent contribution for risk stratification of SCD. METHODS: Patients who had EF ≤ 40% before revascularization and had EF reassessment at least once during follow-up were included. The role of early (<3 months) versus late (3-12 months) EF measurements in prediction of all-cause mortality and SCD were compared. RESULTS: A total of 1589 patients were identified. EF reassessed <3 months was lower than EF reassessed within 3-12 months (42.1 ± 9.7% vs. 45.8 ± 10.8%; p < .01). Among 1069 patients who had EF reassessed <3 months, EF ≤ 35% was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.22-2.29; p < .01), but had no association with the risk of SCD (HR, 1.44; 95% CI, 0.84-2.48; p = .18). By contrast, among 595 patients who had EF reassessed within 3-12 months, EF ≤ 35% was associated with higher risks of both all-cause death (HR, 1.81; 95% CI, 1.06-3.10; p = .03) and SCD (HR, 2.71; 95% CI, 1.31-5.61; p < .01). The relative contribution of SCD to all-cause death was higher in patients with EF ≤ 35% than patients with EF > 35% when EF was reassessed within 3-12 months (p = .04). However, when EF was reassessed <3 months, the mode of death was similar in patients with EF ≤ 35% versus >35% (p = .85). CONCLUSIONS: 3 to 12 months after revascularization may be appropriate for cardiac function reassessment and SCD risk stratification.

Ergosterol peroxide blocks HDV infection as a novel entry inhibitor by targeting human NTCP receptor.

Hepatitis D virus (HDV), which co-infects or superinfects patients with hepatitis B virus, is estimated to affect 74 million people worldwide. Chronic hepatitis D is the most severe form of viral hepatitis and can result in liver cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Currently, there are no efficient HDV-specific drugs. Therefore, there is an urgent need for novel HDV therapies that can achieve a functional cure or even eliminate the viral infection. In the HDV life cycle, agents targeting the entry step of HDV infection preemptively reduce the intrahepatic viral RNA. Human sodium taurocholate co-transporting polypeptide (hNTCP), a transporter of bile acids on the plasma membrane of hepatocytes, is an essential entry receptor of HDV and is a promising molecular target against HDV infection. Here, we investigated the effect of ergosterol peroxide (EP) on HDV infection in vitro and in vivo. EP inhibited HDV infection of hNTCP-expressing dHuS-E/2 hepatocytes by interrupting the early fusion/endocytosis step of HDV entry. Furthermore, molecular modeling suggested that EP hinders LHBsAg binding to hNTCP by blocking access to S267 and V263. In addition, we generated hNTCP-expressing transgenic (Tg) C57BL/6 mice using the Cre/loxP system for in vivo study. EP reduced the liver HDV RNA level of HDV-challenged hNTCP-Cre Tg mice. Intriguingly, EP downregulated the mRNA level of liver IFN-γ. We demonstrate that EP is a bona fide HDV entry inhibitor that acts on hNTCP and has the potential for use in HDV therapies.

Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity.

Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity, safeguarding receptor activation, and facilitating amplification of signal transduction across the cellular membrane. However, cell-surface antigen-induced multimerization (dubbed AIM herein) has not yet been consciously leveraged in chimeric antigen receptor (CAR) engineering for enriching T cell-based therapies. We co-developed ciltacabtagene autoleucel (cilta-cel), whose CAR incorporates two B-cell maturation antigen (BCMA)-targeted nanobodies in tandem, for treating multiple myeloma. Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity. Crystallographic analysis of BCMA-nanobody complexes revealed atomic details of antigen-antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution. BCMA-induced nanobody CAR multimerization enhanced cytotoxicity, alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release, towards myeloma-derived cells. Our results provide a framework for contemplating the AIM approach in designing next-generation CARs.

Animal experimental study on magnetic anchor technique-assisted endoscopic submucosal dissection of early gastric cancer.

BACKGROUND: Gastric cancer (GC) has high morbidity and mortality. Moreover, because GC has no typical symptoms in the early stages, most cases are already in the advanced stages by the time the symptoms appear, thus resulting in poor prognosis and a low survival rate. Endoscopic submucosal dissection (ESD) can realize the early detection and diagnosis of GC and become the main surgical method for early GC. However, ESD has a steep learning curve and high technical skill requirements for endoscopists, which is not conducive to its widespread implementation and advancement. Therefore, a series of auxiliary techniques have been derived. AIM: To evaluate the safety and efficacy of magnetic anchor technique (MAT)-assisted ESD in early GC. METHODS: This was an ex vivo animal experiment. The experimental models were the isolated stomachs of pigs, which were divided into two groups, namely the study group (n = 6) with MAT-assisted ESD and the control group (n = 6) with traditional ESD. Comparing the total surgical time, incidence of surgical complications, complete mucosal resection rate, specimen size, and the scores of endoscopist's satisfaction with the procedure reflected their feelings about convenience during the surgical procedure between the two groups. The magnetic anchor device for auxiliary ESD in the study group comprised three parts, an anchor magnet (AM), a target magnet (TM), and a soft tissue clip. Under gastroscopic guidance, the soft tissue clip and the TM were delivered to the pre-marked mucosal lesion through the gastroscopic operating hole. The soft tissue clip and the TM were connected by a thin wire through the TM tail structure. The soft tissue clip was released by manipulating the operating handle of the soft tissue clip in a way that the soft tissue clip and the TM were fixed to the lesion mucosa. In vitro, ESD is aided by maneuvering the AM such that the mucosal dissection surface is exposed. RESULTS: The total surgical time was shorter in the study group than in the control group (26.57 ± 0.19 vs 29.97 ± 0.28, P < 0.001), and the scores of endoscopist's satisfaction with the procedure were higher in the study group than in the control group (9.53 ± 0.10 vs 8.00 ± 0.22, P < 0.001). During the operation in the study group, there was no detachment of the soft tissue clip and TM and no mucosal tearing. The magnetic force between the AM and TM provided good mucosal exposure and sufficient tissue tension for ESD. The mucosal lesion was completely peeled off, and the operation was successful. There were no significant differences in the incidence of surgical complications (100% vs 83.3%), complete mucosal resection rate (100% vs 66.7%, P = 0.439), and specimen size (2.44 ± 0.04 cm vs 2.49 ± 0.02, P = 0.328) between the two groups. CONCLUSION: MAT-ESD is safe and effective for early GC. It provides a preliminary basis for subsequent internal animal experiments and clinical research.

A Novel Deformable Self-Assembled Magnetic Anastomosis Ring (DSAMAR) for Esophageal Stenosis Recanalization without Temporary Gastrostomy in Beagle Dogs.

BACKGROUND: To assess the feasibility of a deformable self-assembled magnetic anastomosis ring (DSAMAR) in the treatment of esophageal stenosis in beagle dogs via transoral access without temporary gastrostomy. METHODS: Experimental esophageal stenosis was created in 10 beagle dogs by partial cervical esophageal ligation. The DSAMAR was inserted into the distal esophagus via the narrow section of the esophagus using a gastroscope. A circular DSAMAR was placed in the proximal esophagus. The magnetic rings on both sides of the experimental stenosis automatically attracted each other. We then recorded the operation time, postoperative complications, anastomotic formation time, and magnetic ring discharge time. The dogs were euthanized 4 weeks postoperatively; subsequently, we obtained the esophageal anastomotic specimens and observed the anastomotic formation via the naked eye and by light microscopy. RESULTS: Our esophageal stenosis model produced reproducible stenoses in all dogs, which was confirmed via endoscopy and esophagography. DSAMAR was successfully implanted in all experimental animals under endoscopic and X-ray monitoring, and all linear DSAMARs were successfully transformed into rings. The magnets at both ends of the esophageal stenosis were automatically attracted. All animals survived until euthanasia. No complications, including esophageal perforation, bleeding, and gastrointestinal obstruction, were noted during the perioperative period. The mean operation time of endoscopic magnetic anastomosis was 15.6 ± 2.41 (range, 12-19) min. The mean esophageal anastomotic formation time was 8.8 ± 1.03 (range, 7-10) days, and the mean expulsion time of DSAMAR was 13.94 ± 2.88 (range, 10-19) days. Gastroscopy and esophagography were performed at 4 weeks postoperatively; the esophageal patency was good. Macroscopic observation of the esophageal anastomotic specimens revealed that the esophageal mucosal layer of the anastomosis had good continuity and the anastomosis was smooth. CONCLUSION: DSAMAR is a feasible option for magnetic recanalization of esophageal stricture via transoral access without temporary gastrostomy.

Magnetic anchor technique assisted endoscopic submucosal dissection for early esophageal cancer.

BACKGROUND: Esophageal cancer has high incidence globally and is often diagnosed at an advanced stage. With the widespread application of endoscopic technologies, the need for early detection and diagnosis of esophageal cancer has gradually been realized. Endoscopic submucosal dissection (ESD) has become the standard of care for managing early tumors of the esophagus, stomach, and colon. However, due to the steep learning curve, difficult operation, and technically demanding nature of the procedure, ESD has currently been committed to the development of various assistive technologies. AIM: To explore the feasibility and applicability of magnetic anchor technique (MAT)-assisted ESD for early esophageal cancer. METHODS: Isolated pig esophagi were used as the experimental model, and the magnetic anchor device was designed by us. The esophagi used were divided into two groups, namely the operational and control groups, and 10 endoscopists completed the procedure. The two groups were evaluated for the following aspects: The total operative time, perforation rate, rate of whole mucosal resection, diameter of the peering mucosa, and scores of endoscopists' feelings with the procedure, including the convenience, mucosal surface exposure degree, and tissue tension. In addition, in the operational group, the soft tissue clip and the target magnet (TM) were connected by a thin wire through a small hole at the tail end of the TM. Under gastroscopic guidance, the soft tissue clip was clamped to the edge of the lesioned mucosa, which was marked in advance. By changing the position of the anchor magnet (AM) outside the esophagus, the pulling force and pulling direction of the TM could be changed, thus exposing the mucosal peeling surface and assisting the ESD. RESULTS: Herein, each of the two groups comprised 10 isolated esophageal putative mucosal lesions. The diameter of the peering mucosa did not significantly differ between the two groups (2.13 ± 0.06 vs 2.15 ± 0.06, P = 0.882). The total operative time was shorter in the operational group than in the control group (17.04 ± 0.22 min vs 21.94 ± 0.23 min, P < 0.001). During the entire experiment, the TM remained firmly connected with the soft tissue clip and did not affect the opening, closing, and release of the soft tissue clip. The interaction between the TM and AM could provide sufficient tissue tension and completely expose the mucosa, which greatly assists the surgeon with the operation. There was no avulsion of the mucosa, and mucosal lesions were intact when peeled. Therefore, the scores of endoscopists' feelings were higher in the operational group than in the control group in terms of the convenience (9.22 ± 0.19 vs 8.34 ± 0.15, P = 0.002), mucosal surface exposure degree (9.11 ± 0.15 vs 8.25 ± 0.12, P < 0.001), and tissue tension (9.35 ± 0.13 vs 8.02 ± 0.17, P < 0.001). The two groups did not significantly differ in the perforation rate and rate of whole mucosal resection. CONCLUSION: We found MAT-assisted ESD safe and feasible for early esophageal cancer. It could greatly improve the endoscopic operation experience and showed good clinical application prospects.

Value of a novel Y-Z magnetic totally implantable venous access port in improving the success rate of one-time needle insertion.

Background and objectives: A totally implantable venous access port (TIVAP) is a commonly used intravenous infusion device for patients receiving chemotherapy or long-term infusion therapy. To improve the success rate of one-time insertion of the Huber needle, we developed a novel Y-Z magnetic TIVAP (Y-Z MTIVAP), which we produced using three-dimensional printing technology. Materials and methods: The Y-Z MTIVAP includes a magnetic port body and a magnetic positioning device. For testing, we established four venous port implantation models using the two types of TIVAPs and two implantation depth ranges (≤5 mm and >5 mm). Twenty nurses performed Huber needle puncture with the four models, and we recorded the number of attempts required for successful needle insertion, the operation time, and the operator's satisfaction. Results: The success rate for one-time needle insertion with the Y-Z MTIVAP was significantly higher than that with the traditional TIVAP at either depth range (100% vs. 75% at ≤5 mm, p = 0.047; 95% vs. 35% at >5 mm, p < 0.001). With increasing implantation depth, the success rate for one-time insertion was significantly reduced with the traditional TIVAP (75% at ≤5 mm vs. 35% vs. >5 mm, p = 0.025), but the success rate with the Y-Z MTIVAP was not significantly affected (100% vs. 95%, p = 1.000). The operation time with the Y-Z MTIVAP was significantly shorter than that with the traditional TIVAP at either depth range (both p < 0.001), and 90% of operators reported that the Y-Z MTIVAP was superior to the traditional TIVAP. Conclusions: The theoretical design of Y-Z MTIVAP is feasible, and the preliminary in vitro simulation experiment shows that it can significantly improve puncture success rate and shortened operation time.

Novel deformable self-assembled magnetic anastomosis ring for endoscopic treatment of colonic stenosis via natural orifice.

BACKGROUND: Although endoscope-assisted magnetic compression anastomosis has already been reported for colonic anastomosis, there is no report on a single-approach operation using the natural orifice. AIM: To design a deformable self-assembled magnetic anastomosis ring (DSAMAR) for colonic anastomosis for use in single-approach operation and evaluate its feasibility and safety through animal experiments. METHODS: The animal model for colonic stenosis was prepared by partial colonic ligation in eight beagles. The magnetic compression anastomosis of their colonic stricture was performed by endoscopically assisted transanal implantation of the DSAMAR. The anastomotic specimen, obtained 2 wk after the operation, was observed by both the naked eye and a light microscope. RESULTS: The DSAMAR was successfully inserted into the proximal end of colon stenosis through the anus. The DSAMAR of seven dogs was successfully transformed into rings, while that of the remaining dog was removed after the first deformation failed. The rings were successfully retransformed after optimization. All animals underwent colonic anastomosis using the DSAMAR. No device-related or procedure-related adverse events were observed. The colostomy specimens of the experimental dogs were obtained 2 wk after the operation. Both gross and histological observations showed good anastomotic healing. CONCLUSION: The DSAMAR is a safe and feasible option for the treatment of colon stenosis. Its specific deformation and self-assembly capability maximize the applicability of the minimally invasive treatment.

Primary animal experiment to test the feasibility of a novel Y-Z magnetic hepatic portal blocking band.

BACKGROUND: Hepatic portal blood flow occlusion is a common technique for reducing hepatic hemorrhage during hepatectomy. We designed a novel Y-Z magnetic hepatic portal blocking band (Y-Z MHPBB) based on the principle of magnetic compression technique. AIM: To introduce the Y-Z MHPBB device and verify the feasibility of this device for hepatic portal blood flow occlusion in dogs. METHODS: Ten beagles were randomly divided into the experimental group and control group. The operation time, intraoperative blood loss, the number of portal blood flow occlusions, the total time spent on adjusting the blocking band, and the average time spent on adjusting the blocking band were recorded. The surgeons evaluated the feasibility and flexibility of the two portal occlusion devices. RESULTS: Laparoscopic hepatectomy was successfully performed in both the experimental group and control group. There was no statistical difference between the two groups in the operation time, intraoperative blood loss, and the number of hepatic portal blood flow occlusions. With respect to the total time spent on adjusting the blocking band and the average time spent on adjusting the blocking band, the experimental group showed significantly better outcomes than the control group, with a statistical difference (P < 0.05). The operators found that the Y-Z MHPBB was superior to the modified T-tube in terms of operational flexibility. CONCLUSION: The Y-Z MHPBB seems to be an ingenious design, accurate blood flow occlusion effect, and good flexibility; and it can be used for hepatic portal blood flow occlusion during laparoscopic hepatectomy.

Magnetic compression anastomosis for reconstruction of digestive tract after total gastrectomy in beagle model.

BACKGROUND: Magnetic compression anastomosis (MCA) is a simple procedure contributing to a reliable anastomosis. However, digestive-tract reconstruction after total gastrectomy using MCA has not yet been reported. AIM: To investigate the feasibility of MCA for simultaneous esophagojejunostomy and jejunojejunostomy after total gastrectomy using beagle dogs. METHODS: Sixteen beagles were randomly divided into an MCA group (study group, n = 8) and a manual-suture anastomosis group (control group, n = 8). Two different magnetic anastomosis devices were used in the study group for esophagojejunal and jejunojejunal anastomoses. Both devices included a pair of circular daughter and parent magnets each. The time of esophagojejunostomy and jejunojejunostomy, postoperative complications, and survival rate of the two groups were compared. The dogs were sacrificed one month after the operation and their anastomotic specimens were obtained. Healing was observed by the naked eye and a light microscope. RESULTS: Digestive-tract reconstruction after total gastrectomy was successfully completed in both groups (survival rate = 100%). In the study group, esophagojejunal and jejunojejunal anastomoses took 6.13 ± 0.58 and 4.06 ± 0.42 min, respectively, significantly lower than those in the control group (15.63 ± 1.53 min, P < 0.001 and 10.31 ± 1.07 min, P < 0.001, respectively). Complications such as bleeding, anastomotic leakage, and anastomotic stenosis were not observed. In the study group, the magnets did not interfere with each other. Discharge time of the jejunojejunal magnetic anastomosis device was 10.75 ± 1.28 d, while that of the esophagojejunal magnetic anastomosis device was 12.25 ± 1.49 d. Residual silk was found in the control group. The study group showed a greater smoothness of the anastomosis than that of the control group. All layers of anastomosis healed well in both groups. CONCLUSION: MCA is a safe and feasible procedure for digestive-tract reconstruction after total gastrectomy in this animal model.

Phenethyl isothiocyanate induces oxidative cell death in osteosarcoma cells with regulation on mitochondrial network, function and metabolism.

Phenethyl isothiocyanate (PEITC), a kind of isothiocyanate available in cruciferous vegetables, exhibits inhibitory effects on cancers. PEITC has been extensively recorded for its effect on regulation of redox status in cancer cells. Our previous studies revealed that PEITC induced ROS-dependent cell death in osteosarcoma. Mitochondria are the main sites for ROS generation and play significant role in deciding cell fate. To dissect the mechanism of PEITC's action on osteosarcoma cells, we detected the changes on mitochondrial network, function and metabolism in K7M2 and 143B cells. Here, PEITC induced cytosolic, lipid and mitochondrial ROS production in osteosarcoma cells. It changed mitochondrial morphology from elongated to punctate network and decreased mitochondrial mass. Meantime, PEITC increased mitochondrial transmembrane potential in short time, decreased it with time prolonged, and later collapsed it in K7M2 cells, and reduced it in 143B cells. PEITC inhibited proliferation potential of osteosarcoma cells with damage on mitochondrial respiratory chain complexes. Further, PEITC-treated osteosarcoma cells experienced a sudden increase in ATP level, and later its content was decreased. Moreover, PEITC downregulated the expressions of mitochondrial respiratory chain complexes including COX IV, UQCR, SDHA and NDUFA9 in 143B cells and COX IV in K7M2 cells. At last, by using ρ0 cells derived from K7M2 and 143B cells, we found that osteosarcoma cells that depleted mtDNA were less sensitive to PEITC-induced changes on cellular morphology, cytoskeleton filament, mitochondrial transmembrane potential and ROS generation. In conclusion, our study demonstrated that mitochondria may play important role in PEITC-induced oxidative cell death in osteosarcoma cells.