Multidisciplinary management of ulcerative colitis complicated by immune checkpoint inhibitor-associated colitis with life-threatening gastrointestinal hemorrhage:A case report

BACKGROUND Programmed cell death 1(PD-1)inhibitors are immune checkpoint inhibitors(ICI)that have demonstrated significant efficacy in treating various advanced malignant tumors.While most patients tolerate treatment well,several adverse drug reactions,such as fatigue,myelosuppression,and ICI-associated colitis,have been reported.CASE SUMMARY This case involved a 57-year-old male patient with ulcerative colitis complicated by hepatocarcinoma who underwent treatment with tirelizumab(a PD-1 inhibitor)for six months.The treatment led to repeated life-threatening lower gastrointestinal hemorrhage.The patient received infliximab,vedolizumab,and other salvage procedures but ultimately required subtotal colectomy due to uncontrollable massive lower gastrointestinal bleeding.Currently,postoperative gastrointestinal bleeding has stopped,the patient’s stool has turned yellow,and his full blood cell count has returned to normal.CONCLUSION This case highlights the necessity of early identification,timely and adequate treatment of ICI-related colitis,and rapid escalation to achieve the goal of improving prognosis.

Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular networks.Brain vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the brain.This elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing vasculature.Brain capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

case of familial hyperlipoproteinemia type Ⅲ hypertriglyceridemia induced acute pancreatitis: role for outpatient apheresis maintenance therapy

Hypertriglyceridemic pancreatitis(HTGP) accounts for up to 10% of acute pancreatitis presentations in nonpregnant individuals and is the third most common cause of acute pancreatitis after alcohol and gallstones. There are a number of retrospective studies and case reports that have suggested a role for apheresis and insulin infusion in the acute inpatient setting. We report a case of HTGP in a male with hyperlipoproteinemia type Ⅲ who was treated successfully with insulin and apheresis on the initial inpatient presentation followed by bi-monthly outpatient maintenance apheresis sessions for the prevention of recurrent HTGP. We also reviewed the literature for the different inpatient and outpatient management modalities of HTGP. Given that there are no guidelines or randomized clinical trials that evaluate the outpatient management of HTGP, this case report may provide insight into a possible role for outpatient apheresis maintenance therapy.

Kangaroo Care (Skin-to-Skin) for Clustered Pain Procedures: Case Study

Background: Pain management for term newborns undergoing clustered painful procedures has not been tested. Kangaroo Care (chest-to-chest, skin-to-skin position of infant on mother) effectively reduces pain of single procedures, but its effect on pain from clustered procedures is not known. Aim: The aim was to test Kangaroo Care’s effect on pain in one term infant who received clustered painful procedures while determining feasibility of the Kangaroo Care intervention. Design, Setting, and Participant: A case study design was used with one healthy term newborn who received two heel sticks and one injection in one session in the mother’s postpartum room. Method: Heart rate and oxygen saturation (recorded from Massimo Pulse Oximeter every 30 seconds), crying time (total seconds of crying on videotape) and behavioral state (using Anderson Behavioral State Scoring system every 30 seconds) were measured before (5 minutes), during (10.5 minutes) and after (30 minutes) the three clustered painful procedures in a newborn who was in Kangaroo Care during all observations. One staff nurse administered the clustered procedures. Results: Heart rate increased sequentially with each heelstick, oxygen saturation remained unchanged, sleep predominated, and crying was minimal throughout the procedures. Conclusion: Kangaroo Care appeared to reduce pain from clustered painful procedures and can be further tested.

Immunotherapy of Malignant Tumors Using Antisense Anti-IGF-I Approach: Case of Glioblastoma

The review article describes the criteria established for methodology of antisense anti IGF-I therapy of malignant tumors, particularly of glioblastoma. The cancer patients, after classical therapy of surgery, radiotherapy and chemotherapy, have undergone the injection of genetically modified autologous malignant cells—transfected by IGF-I antisense/triple helix expression vectors. For all cancer patients supervised for up to 19 months, the period corresponding to minimum survival of glioblastoma patients, the following common immune criteria for “anti IGF-I” strategy were admitted: 1) characteristics of cell “vaccines”—absence of IGF-I and expression of MHC-I in cloned transfected cells;2) the peripheral blood lymphocytes, PBL cells, removed after every of two successive vaccinations, demonstrate an increasing level of CD8+ and CD8+28+ molecules (with a switch from CD8+11b+ to CD8+11b-).

Gallstone ileus associated with impaction at Meckel's diverticulum:Case report and literature review

Gallstone ileus due to erosion of one or more gallstones into the gastrointestinal tract is an uncommon cause of small bowel obstruction. The site of impaction is usually distal ileum, and less commonly the jejunum, colon, duodenum, or stomach. We report a rare case of gallstone ileus with impaction at the proximal small bowel and at a Meckel's diverticulum(MD) in a 64-yearold woman managed with laparoscopic converted to open small bowel resections. Patient was discharged home in stable condition and remained asymptomatic at 6-mo follow up. We review the current literature on surgical approaches to MD and gallstone ileus. Diverticulectomy or segmental resection is preferred for complicated MD. For gallstone ileus, simple enterolithotomy or segmental resection are the most the most favored especially in older co-morbid patients due to lower mortality rates and the rarity of recurrent gallstone ileus. In addition, laparoscopy has been increasingly reported as a safe approach to manage gallstone ileus.

Isolated colonic neurofibroma, a rare tumor: A case report and review of literature

BACKGROUND Neurofibromas are tumors comprised of peripheral nerve sheath and connective tissue components.They can occur sporadically or as part of familial syndromes such as neurofibromatosis type 1.Isolated colonic neurofibroma without systemic manifestations is a rarely reported clinical entity.Here we present a case of a 51 years old male with an isolated colonic neurofibroma seen on a screening colonoscopy.CASE SUMMARY Fifty-one years old male who was otherwise healthy without a significant family history of cancer underwent a screening colonoscopy and was found have a 2.3 cm×1.4 cm lesion in the colon.Tissue biopsy revealed a spindle cell tumor.Magnetic resonance imaging of the pelvis was negative for adenopathy.He underwent an endoscopic ultrasound that showed an ill-defined avascular lesion of mixed echogenicity measuring 2.8 cm×15.2 cm in the submucosa with no communication with muscularis mucosa or propria.Immunohistochemistry staining of the tumor was strongly positive for S100,with rare penetrating axons deep within the tumor.Tumor cells were negative for c-kit and desmin and had low Ki-67 index.These findings were consistent with a solitary colonic submucosal neurofibroma.A detailed history and physical examination did not reveal any evidence of extraintestinal neurofibromatosis.He underwent transanal surgical resection of the tumor.The patient tolerated the procedure well without any complications.CONCLUSION While neurofibromas have been well described in literature,an isolated colonic neurofibroma is a rare pathological entity.Malignant transformation of neurofibromas has been reported in patients with neurofibromatosis syndromes.We report a case of isolated colonic neurofibroma and highlight the importance of resection due to the increased risk of tumorigenesis.

Spinal cord infarction attributed to SARS-CoV-2, with post-acute sequelae of COVID-19: A case report

BACKGROUND While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),spinal cord infarction or ischemia has been extremely rare.Findings of long coronavirus disease(COVID)in this select population have not been studied.CASE SUMMARY We present the case of a 70-year-old female with sudden onset of trunk and lower extremity sensorimotor loss due to spinal cord infarction,attributed to acute infection with SARS-CoV-2.Diagnostic work up confirmed a T3 complete(ASIA impairment Scale A)paraplegia resulting from a thrombotic infarct.Her reported myalgias,neuropathic pain,spasticity,bladder spasms,and urinary tract infections exceeded the frequency and severity of many spinal cord injury(SCI)individuals of similar age and degree of neurologic impairment.In her first year after contracting COVID-19,she underwent 2 separate inpatient rehabilitation courses,but also required acute hospitalization 6 additional times for subsequent infections or uncontrolled pain.Yet other complications of complete non-traumatic SCI(NTSCI),including neurogenic bowel and temperature hypersens-itivity,were mild,and pressure injuries were absent.She has now transitioned from the acute to chronic phase of spinal cord injury care,with subsequent development of post-acute sequelae of SARS-CoV-2 infection(PASC).CONCLUSION This individual experienced significant challenges with the combined effects of acute T3 NTSCI and acute COVID-19,with subsequent progression to PASC.Core Tip:Although stroke and venous thromboembolism have been frequently observed with acute coronavirus disease 2019(COVID-19),spinal cord infarction leading to paraplegia has rarely been seen.We report a case of spinal cord infarction shortly following infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Consequently,this individual has experienced severe neurologic disability,with subsequent development of long COVID.Symptoms such as myalgias,neuropathic pain,muscle spasms,and frequent bacterial infections are present in post-acute sequelae of SARS-CoV-2 infection(PASC),independent of spinal cord injury(SCI).Over the past 3 years,the dual presence of PASC and recent SCI may have led to increased severity of symptoms shared by both conditions.INTRODUCTION Among vascular events,spinal cord infarction is relatively rare,accounting for only 0.3%-1%of all strokes[1]and 5%-8%of acute myelopathies[2].One cause of spinal cord infarction arises from a thrombotic event in vulnerable areas of the thoracic cord,particularly between T8-12,which is supplied by the artery of Adamkiewicz.While deep vein thrombosis,pulmonary embolism,and stroke are commonly observed complications of coronavirus disease 2019(COVID-19),spinal cord infarction is comparatively infrequent[3-6].The cytokine release following acute infection,which peaks 7 d after contracting the virus,may be responsible for the increase in thrombotic events associated with acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[7,8].This case discussed in this report differs from other published accounts describing spinal cord infarcts attributed to acute SARS-CoV-2,because we have followed this individual for nearly 3 years after contracting COVID-19,covering her difficulties with“long COVID,”which has now officially named post-acute sequelae of SARS-CoV-2 infection(PASC)by the World Health Organization[9].The term PASC may be assigned to“individuals with a history of probable or confirmed SARS-CoV-2 infection,usually 3 mo from the onset of COVID-19 with symptoms that last for at least 2 mo and cannot be explained by an alternative diagnosis”.The definition further states that PASC generally impacts everyday functioning and that symptoms may be of new onset,follow initial recovery from an acute COVID-19 episode,or persist from the initial illness.Moreover,symptoms may also fluctuate or relapse over time[9].Common complaints of PASC include fatigue,cough shortness of breath,cognitive deficits or“brain fog”.Reported features of PASC may also involve headache,heart palpitations,exercise intolerance,joint pain or swelling,myalgias,vertigo,peripheral neuropathy,altered taste or smell,disordered sleep,anxiety,depression,and thromboembolic events[10-13].While a number of the above symptoms may occur subsequent to SCI,many would be unusual,such as persistent cough,fatigue months after SCI,changes in taste or smell,continued exercise intolerance,new onset cognitive deficits or“brain fog”,unrelated to any sedating medications or concomitant brain injury.Our patient became symptomatic prior to COVID-19 vaccine availability and has given written consent to share her story for educational publication.This project was approved by the Institutional Review Board of the MetroHealth System.

Pediatric-type follicular lymphoma in a Crohn’s disease patient receiving anti-α4β7-integrin therapy:A case report

BACKGROUND Patients with autoimmune conditions receiving immunosuppressants are at risk of non-Hodgkin lymphomas(NHL).Vedolizumab(anti-α4β7-integrin antibody),a treatment-of-choice for Crohn’s disease(CD),reduces inflammatory lymphocyte trafficking into the intestinal mucosa.This effect is believed to be confined to the colon.CASE SUMMARY We report the case of a CD patient on vedolizumab for five years who developed pediatric-type follicular lymphoma.Work-up prior to therapy revealed a reduction in circulating T-lymphocytes and their suppressed response to mitogens.Rituximab,cyclophosphamide,vincristine,and prednisone chemoimmunotherapy resulted in durable lymphoma remission,and vedolizumab treatment was continued.While the patient’s T-lymphocyte population and immunoglobulin production recovered,the T-lymphocyte mitogen response remained suppressed.CONCLUSION This patient’s NHL may be linked to receiving anti-α4β7 therapy.Further research could be beneficial to determine if proactive surveillance for NHL and other systemic diseases is indicated in patients on vedolizumab.

Improved Pregnancy Outcomes in a Prospective Study of Pregnant Women Enrolling in an Antenatal Clinic in Western Kenya

In areas of sub-Saharan Africa where malaria is endemic, pregnant women are at a greater risk of malaria than non-pregnant women leading to significant adverse consequences including anemia, intrauterine growth retardation, low birth weight (LBW), and pre-term delivery. The Kenya Ministry of Health adopted Intermittent Preventive Treatment (IPT) and use of insecticide-treated nets (ITN) as a National strategy for malaria prevention in pregnancy. In this report, we evaluated the prevalence of malaria, the anthropometric measures of birth outcomes and the reasons for loss to follow up among pregnant women participating in an ongoing cohort study in Western Kenya. A total of 175 HIV-negative pregnant women enrolled at antenatal clinic of Chulaimbo sub-District hospital were longitudinally evaluated in a monthly follow-up visits through antenatal visits (up to 4 per mother) and delivery. Thirty three percent and 15% of the pregnant women were malaria positive by real-time quantitative (Q)-PCR and microscopy respectively at enrolment, while 54% and 23% of the pregnant women had malaria by Q-PCR and microscopy respectively at any time during follow-up. Of the enrolled study participants, 65% delivered at Chulaimbo hospital. Overall, 39% (69) of the pregnant women were lost to follow-up. The major reasons for loss to follow up were relocation from the study area (26%) and delivery at alternative health facilities (25%). The mean birth weight of the newborn infants was 3202 g (range, 2000 g - 4000 g). Only 5.3% of the infants weighed less than 2500 g (low birth weight). The mean head circumference was 34 cm (range, 30 cm - 39 cm) with mean Apgar score (at 10 minutes) ± S.D. of 9.8 ± 0.97. In conclusion, we observed decreased adverse pregnancy outcomes among our study population. We recommend a larger study of all pregnant women attending the Chulaimbo hospital so as to assess whether effectiveness of malaria and anemia control programs lead to improved birth outcomes.

高分子多层共挤技术的研究进展

高分子多层共挤技术是一项利用特制的挤出模具将两种高分子材料制成成百上千层薄膜的技术,可突破传统高分子复合材料相分离的限制,实现不同高分子材料的有效结合。高分子多层共挤技术产生的纳米效应、界面效应和结构效应具有广泛的应用性:纳米效应可对高分子晶体晶型和取向进行有效调控;界面效应是研究高分子材料相互作用的有效手段,可用于制造全界面材料等新型材料;结构效应具有独特的光学意义,利用一维有序层状结构产生一维光子晶体并结合高分子材料取向的特点,可对光反射和折射产生独特的影响。高分子多层膜在众多领域拥有良好的科研和应用价值。

Brain-wide activation involved in 15 mA transcranial alternating current stimulation in patients with first-episode major depressive disorder

Background Although 15 mA transcranial alternating current stimulation(tACS)has a therapeutic effect on depression,the activations of brain structures in humans accounting for this tACS configuration remain largely unknown.Aims To investigate which intracranial brain structures are engaged in the tACS at 77.5 Hz and 15 mA,delivered via the forehead and the mastoid electrodes in the human brain.Methods Actual human head models were built using the magnetic resonance imagings of eight outpatient volunteers with drug-naïve,first-episode major depressive disorder and then used to perform the electric field distributions with SimNIBS software.Results The electric field distributions of the sagittal,coronal and axial planes showed that the bilateral frontal lobes,bilateral temporal lobes,hippocampus,cingulate,hypothalamus,thalamus,amygdala,cerebellum and brainstem were visibly stimulated by the 15 mA tACS procedure.Conclusions Brain-wide activation,including the cortex,subcortical structures,cerebellum and brainstem,is involved in the 15 mA tACS intervention for first-episode major depressive disorder.Our results indicate that the simultaneous involvement of multiple brain regions is a possible mechanism for its effectiveness in reducing depressive symptoms.

ATP6AP2,a regulator of LRP6/β-catenin protein trafficking,promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner

Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and function.Exactly how Wnt/β-catenin signaling is regulated in OBs remain elusive.ATP6AP2,an accessory subunit of V-ATPase,plays important roles in multiple cell types/organs and multiple signaling pathways.However,little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone formation.Here we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone regions.Conditionally knocking out(CKO)ATP6AP2 in the OB-lineage cells(Atp6ap2^(Ocn-Cre))reduced trabecular,but not cortical,bone formation and bone mass.Proteomic and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs,but not osteocytes.Additional in vitro and in vivo studies revealed impairedβ-catenin signaling in ATP6AP2-KO BMSCs and OBs,but not osteocytes,under both basal and Wnt stimulated conditions,although LRP5 was decreased in ATP6AP2-KO osteocytes,but not BMSCs.Further cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression ofβ-catenin phosphorylation,but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane,thus preventing their degradation.Expression of activeβ-catenin diminished the OB differentiation deficit in ATP6AP2-KO BMSCs.Taken together,these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability,and thus regulatingβ-catenin levels,demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.

Percutaneous decannulation of extracorporeal membrane oxygenation using MANTA device:A real-world single-center experience

BACKGROUND The MANTA vascular closure device(VCD)represents a novel approach to achieving hemostasis after large-bore femoral access procedures.Numerous clinical studies have evaluated the efficacy of the MANTA device across a range of patient populations undergoing different procedures.However,there is still a paucity of data available concerning the use of MANTA devices in aiding the decannulation of venoarterial extracorporeal membrane oxygenation(VAECMO).AIM To present our single-center experience of utilizing the MANTA VCD in patients undergoing this procedure.METHODS This single-center study included all patients undergoing percutaneous decannulation of femoral VA-ECMO using the MANTA plug-based VCD between January 2021 and October 2023 at University Hospitals Cleveland Medical Center.Inclusion criteria were adult patients who required prolonged(>24 hours)hemodynamic support with VA-ECMO.Outcomes included all-cause mortality,hemostasis,bleeding,limb ischemia,and site infection.RESULTS This is a retrospective cohort study of 19 patients with a mean age of 56.8 years.Twelve of them were males with a mean body mass index of 29.The most common extracorporeal membrane oxygenation indication was acute coronary syndrome complicated by cardiogenic shock at 36.8%.The mean length of intensive care unit stay for these patients was 18.8±8.42 days.Seventeen out of 19 patients survived to discharge.The MANTA device was successfully deployed in 19 patients,with 10 procedures conducted at the bedside and 9 in an operating room setting.Complete hemostasis was achieved within 5 minutes of MANTA deployment in 17 out of 19 patients.In 2 patients manual compression after Manta deployment was required to achieve adequate hemostasis.Additionally,acute lower extremity ischemia was noted in two patients,necessitating endovascular interventions.No infections were reported at the site of MANTA deployment.CONCLUSION Overall,based on our experience and that of other centers,the MANTA VCD has proven to be a simple,safe,and effective percutaneous technique for facilitating in the OR,but most of all it opens the opportunity for bedside VAECMO decannulation.Post-decannulation ischemic complications are higher in this series of sick patients when compared with elective procedures like transcatheter aortic valve replacement and endovascular aneurysm repair.Additionally,operators should be mindful of the incidence of ischemic complications.Distal Doppler pulse signals should always be checked,to indicate bailout options when this occurs.

Predicting hepatocellular carcinoma: A new non-invasive model based on shear wave elastography

BACKGROUND Integrating conventional ultrasound features with 2D shear wave elastography(2D-SWE)can potentially enhance preoperative hepatocellular carcinoma(HCC)predictions.AIM To develop a 2D-SWE-based predictive model for preoperative identification of HCC.METHODS A retrospective analysis of 884 patients who underwent liver resection and pathology evaluation from February 2021 to August 2023 was conducted at the Oriental Hepatobiliary Surgery Hospital.The patients were divided into the modeling group(n=720)and the control group(n=164).The study included conventional ultrasound,2D-SWE,and preoperative laboratory tests.Multiple logistic regression was used to identify independent predictive factors for RESULTS In the modeling group analysis,maximal elasticity(Emax)of tumors and their peripheries,platelet count,cirrhosis,and blood flow were independent risk indicators for malignancies.These factors yielded an area under the curve of 0.77(95%confidence interval:0.73-0.81)with 84%sensitivity and 61%specificity.The model demonstrated good calibration in both the construction and validation cohorts,as shown by the calibration graph and Hosmer-Lemeshow test(P=0.683 and P=0.658,respectively).Additionally,the mean elasticity(Emean)of the tumor periphery was identified as a risk factor for microvascular invasion(MVI)in malignant liver tumors(P=0.003).Patients receiving antiviral treatment differed significantly in platelet count(P=0.002),Emax of tumors(P=0.033),Emean of tumors(P=0.042),Emax at tumor periphery(P<0.001),and Emean at tumor periphery(P=0.003).CONCLUSION 2D-SWE’s hardness value serves as a valuable marker for enhancing the preoperative diagnosis of malignant liver lesions,correlating significantly with MVI and antiviral treatment efficacy.

Inhibition of Ehrlich ascites carcinoma growth by melatonin:Studies with micro-CT

Melatonin is a versatile indolamine synthesized and secreted by the pineal gland in response to the photoperiodic information received by the retinohypothalamic signaling pathway.Melatonin has many benefits,such as organizing circadian rhythms and acting as a powerful hormone.We aimed to show the antitumor effects of melatonin in both in vivo and in vitro models through the mammalian target of rapamycin(mTOR)signaling pathway and the Argyrophilic Nucleolar Regulatory Region(AgNOR),using the Microcomputed Tomography(Micro CT).Ehrlich ascites carcinoma(EAC)cells were administered into the mice by subcutaneous injection.Animals with solid tumors were injected intraperitoneally with 50 and 100 mg/kg melatonin for 14 days.Volumetric measurements for the taken tumors were made with micro-CT imaging,immunohistochemistry(IHC),real-time polymerase chain reaction(PCR)and AgNOR.Statistically,the tumor tissue volume in the Tumor+100 mg/kg melatonin group was significantly lower than that in the other groups in the data obtained from micro-CT images.In the IHC analysis,the groups treated with Tumor+100 mg/kg melatonin were compared when the mTOR signaling pathway and factor 8(F8)expression were compared with the control group.It was determined that there was a significant decrease(p<0.05).Significant differences were found in the total AgNOR area/nuclear area(TAA/NA)ratio in the treatment groups(p<0.05).Furthermore,there were significant differences between the amount of mTOR mRNA for the phosphatidylinositol 3-kinase(PI3K),AKT Serine/Threonine Kinase(PKB/AKT)genes(p<0.05).Cell apoptosis was evaluated with Annexin V in an in vitro study with different doses of melatonin;It was observed that 100µg/mL melatonin dose caused an increase in the apoptotic cell death.In this study,we have reported anti-tumor effects of melatonin in cell culture studies as well as in mice models.Comprehensive characterization of the melatonin-mediated cancer inhibitory effects will be valuable in advancing our fundamental molecular understanding and translatability of pre-clinical findings to earlier phases of clinical trials.

Impact of index admission cholecystectomy vs interval cholecystectomy on readmission rate in acute cholangitis: National Readmission Database survey

BACKGROUND Elective cholecystectomy(CCY)is recommended for patients with gallstone-related acute cholangitis(AC)following endoscopic decompression to prevent recurrent biliary events.However,the optimal timing and implications of CCY remain unclear.AIM To examine the impact of same-admission CCY compared to interval CCY on patients with gallstone-related AC using the National Readmission Database(NRD).METHODS We queried the NRD to identify all gallstone-related AC hospitalizations in adult patients with and without the same admission CCY between 2016 and 2020.Our primary outcome was all-cause 30-d readmission rates,and secondary outcomes included in-hospital mortality,length of stay(LOS),and hospitalization cost.RESULTS Among the 124964 gallstone-related AC hospitalizations,only 14.67%underwent the same admission CCY.The all-cause 30-d readmissions in the same admission CCY group were almost half that of the non-CCY group(5.56%vs 11.50%).Patients in the same admission CCY group had a longer mean LOS and higher hospitalization costs attrib-utable to surgery.Although the most common reason for readmission was sepsis in both groups,the second most common reason was AC in the interval CCY group.CONCLUSION Our study suggests that patients with gallstone-related AC who do not undergo the same admission CCY have twice the risk of readmission compared to those who undergo CCY during the same admission.These readmis-sions can potentially be prevented by performing same-admission CCY in appropriate patients,which may reduce subsequent hospitalization costs secondary to readmissions.

Functionally graded structure of a nitride-strengthened Mg_(2)Si-based hybrid composite

The ex-situ incorporation of the secondary SiC reinforcement,along with the in-situ incorporation of the tertiary and quaternary Mg_(3)N_(2) and Si_(3)N_(4) phases,in the primary matrix of Mg_(2)Si is employed in order to provide ultimate wear resistance based on the laser-irradiation-induced inclusion of N_(2) gas during laser powder bed fusion.This is substantialized based on both the thermal diffusion-and chemical reactionbased metallurgy of the Mg_(2)Si–SiC/nitride hybrid composite.This study also proposes a functional platform for systematically modulating a functionally graded structure and modeling build-direction-dependent architectonics during additive manufacturing.This strategy enables the development of a compositional gradient from the center to the edge of each melt pool of the Mg_(2)Si–SiC/nitride hybrid composite.Consequently,the coefficient of friction of the hybrid composite exhibits a 309.3%decrease to–1.67 compared to–0.54 for the conventional nonreinforced Mg_(2)Si structure,while the tensile strength exhibits a 171.3%increase to 831.5 MPa compared to 485.3 MPa for the conventional structure.This outstanding mechanical behavior is due to the(1)the complementary and synergistic reinforcement effects of the SiC and nitride compounds,each of which possesses an intrinsically high hardness,and(2)the strong adhesion of these compounds to the Mg_(2)Si matrix despite their small sizes and low concentrations.

The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.

纳米复合金属氧化物的制备、表征和气敏性质研究

采用硝酸铜、硝酸铈为先驱物 ,乙二醇作溶剂 ,以改进的溶胶 凝胶法制备了纳米结构CuO/CeO2 稀土复合氧化物 .表征结果表明 ,制得的纳米材料的粒径为 15nm左右 ,而二次分布在2 0～ 5 0nm之间 .考察了焙烧温度、不同CuO含量复合材料敏感元件对CO ,H2 ,C2 H5OH ,C6 H6等气体的灵敏度影响 .从实验得出 ,最佳焙烧温度为 6 0 0℃ ,CuO含量为 12 % ,掺入少量贵金属气敏性质得到进一步改进 ,是由掺杂质和复合物之间电子和化学叠加效应所致 .通过制备过程参数控制 ,裁剪出高热稳定和最佳组成的纳米复合材料 ,对监测环境有毒和可燃气体具有较高灵敏度和选择性 .研究结果也为稀土和过渡金属复合氧化物催化剂的制备与催化性质的研究提供了有益的借鉴 .