Going straight for the gut:gut-brain axis pathology and treatment of Parkinson's disease

This perspective focuses on the recent literature regarding the role of the gut-brain axis(GBA) in fecal microbiota transplantation(FMT) and stem cell therapy(SCT) in Parkinson's disease(PD).PD is the second most common neurodegenerative disease in the United States,yet therapies remain limited.Current research suggests that the GBA may play a role in the pathogenesis of PD.GBAbased FMT as well as SCT offer promising new avenues for PD treatment.Pro bing the interactions between FMT and SCT with the GBA may reveal novel therapeutics for PD.

Using MsfNet to Predict the ISUP Grade of Renal Clear Cell Carcinoma in Digital Pathology Images

Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selection.This study presents a new deep network called Multi-scale Fusion Network(MsfNet),which aims to enhance the automatic ISUP grade of ccRCC with digital histopathology pathology images.The MsfNet overcomes the limitations of traditional ResNet50 by multi-scale information fusion and dynamic allocation of channel quantity.The model was trained and tested using 90 Hematoxylin and Eosin(H&E)stained whole slide images(WSIs),which were all cropped into 320×320-pixel patches at 40×magnification.MsfNet achieved a micro-averaged area under the curve(AUC)of 0.9807,a macro-averaged AUC of 0.9778 on the test dataset.The Gradient-weighted Class Activation Mapping(Grad-CAM)visually demonstrated MsfNet’s ability to distinguish and highlight abnormal areas more effectively than ResNet50.The t-Distributed Stochastic Neighbor Embedding(t-SNE)plot indicates our model can efficiently extract critical features from images,reducing the impact of noise and redundant information.The results suggest that MsfNet offers an accurate ISUP grade of ccRCC in digital images,emphasizing the potential of AI-assisted histopathological systems in clinical practice.

A Multi-Task Deep Learning Framework for Simultaneous Detection of Thoracic Pathology through Image Classification

Thoracic diseases pose significant risks to an individual's chest health and are among the most perilous medical diseases. They can impact either one or both lungs, which leads to a severe impairment of a person’s ability to breathe normally. Some notable examples of such diseases encompass pneumonia, lung cancer, coronavirus disease 2019 (COVID-19), tuberculosis, and chronic obstructive pulmonary disease (COPD). Consequently, early and precise detection of these diseases is paramount during the diagnostic process. Traditionally, the primary methods employed for the detection involve the use of X-ray imaging or computed tomography (CT) scans. Nevertheless, due to the scarcity of proficient radiologists and the inherent similarities between these diseases, the accuracy of detection can be compromised, leading to imprecise or erroneous results. To address this challenge, scientists have turned to computer-based solutions, aiming for swift and accurate diagnoses. The primary objective of this study is to develop two machine learning models, utilizing single-task and multi-task learning frameworks, to enhance classification accuracy. Within the multi-task learning architecture, two principal approaches exist soft parameter sharing and hard parameter sharing. Consequently, this research adopts a multi-task deep learning approach that leverages CNNs to achieve improved classification performance for the specified tasks. These tasks, focusing on pneumonia and COVID-19, are processed and learned simultaneously within a multi-task model. To assess the effectiveness of the trained model, it is rigorously validated using three different real-world datasets for training and testing.

Axial length,vitreoretinal pathology,and anterior chamber depth can predict postoperative refractive outcomes in phacovitrectomy/silicone oil removal

AIM:To evaluate the postoperative refractive prediction error(PE)and determine the factors that af fect the refractive outcomes of combined pars plana vitrectomy(PPV)or silicone oil removal(SOR)with cataract surgery.METHODS:The study is a retrospective,case-series study.Totally 301 eyes of 301 patients undergoing combined PPV/SOR with cataract surgery were enrolled.Eligible individuals were separated into four groups according to their preoperative diagnoses:silicone oil-filled eyes after PPV(group 1),epiretinal membrane(group 2),macular hole(group 3),and primary retinal detachment(RD;group 4).The variables af fecting postoperative refractive outcomes were analyzed,including age,gender,preoperative best-corrected visual acuity(BCVA),axial length(AL),keratometry average,anterior chamber depth(ACD),intraocular tamponade,and vitreoretinal pathology.The outcome measurements include the mean refractive PE and the proportions of eyes with a PE within±0.50 diopter(D)and±1.00 D.RESULTS:For all patients,the mean PE was-0.04±1.17 D,and 50.17%of patients(eyes)had a PE within±0.50 D.There was a significant difference in refractive outcomes among the four groups(P=0.028),with RD(group 4)showing the least favorable refractive outcome.In multivariate regression analysis,only AL,vitreoretinal pathology,and ACD were strongly associated with PE(all P<0.01).Univariate analysis revealed that longer eyes(AL>26 mm)and a deeper ACD were correlated with hyperopic PE,and shorter eyes(AL<26 mm)and a shallower ACD were correlated with myopic PE.CONCLUSION:RD patients have the least favorable refractive outcome.AL,vitreoretinal pathology,and ACD are strongly associated with PE in the combined surgery.These three factors affect refractive outcomes and thus can be used to predict a better postoperative refractive outcome in clinical practice.

Aquaporin 5 in Alzheimer’s disease:a link between oral and brain pathology?

The involvement of aquaporins(AQPs)in the development of diseases has been widely described(Azad et al.,2021).AQP5 has been described in astrocytes changing after traumatic brain injuries(Chai et al.,2013),but the precise role of AQP5 in Alzheimer’s disease(AD)pathology is yet to be understood.We have recently reported that AQP5 expression changes during the development of AD(Antequera et al.,2022).The AQP5 expression in salivary glands is decreased in 6-month-old APP/PS1 mice and AD patients.This decrease in AQP5 expression could be involved in the mechanism of salivary gland dysfunction described in a previous study(Antequera et al.,2021).Now,we propose a new indirect role of AQP5 in the connection between infection-induced oral dysbiosis and AD(Sureda et al.,2020).Here,we suggest that the proinflammatory response induced by oral pathogen infection results in the downregulation of AQP5 contributing to the salivary gland secretory dysfunction.All these alterations destabilize the peripheral immune-inflammatory balance and exacerbate neuroinflammation and neurodegeneration leading to AD pathology.

Effects of alendronate on bone mass and organ pathology in ovariectomized mice

Objective:To investigate the effect of alendronate on bone mass and organ pathology of ovariectomized mice.Methods:Thirty SPF grade C57 female mice were randomly divided into three groups(n=10):Sham operation group(Sham),ovariectomized group(OVX)and ovariectomized+alendronate group(ALN).The sodium alendronate was injected subcutaneously at 400μg/kg twice a week in the ALN group.The equal volume of normal saline was injected subcutaneously twice a week in the SHAM group and OVX group.After 12 weeks of drug administration,the samples were taken.The organ coefficients,main organ pathological sections,and bone histopathological sections were observed,and the micro CT,L4 biomechanics and serum biochemical indicators were analyzed.Results:The uterine coefficient of Sham group was(0.0054±0.0007)significantly higher than that of OVX group(0.0026±0.0009)and ALN group(0.0025±0.0007),and the difference was statistically significant(P<0.05).No obvious lesions or toxic or side effects were observed in the main organs.Compared with the OVX group,the ALN group with decalcified sections of bone tissue had compact trabecular structure and fewer adipocytes.Micro-CT results showed that the Tb.BMD,Tb.N,Tb.Th and Tb.BV/TV values of the ALN group were significantly increased compared with those of the OVX group,but the Tb.Sp value was significantly decreased,and the difference was statistically significant(P<0.05).In L4 vertebral body biomechanics,the elastic modulus(50.29±13.43)and maximum load number(29.83±4.92)of ALN group were significantly higher than those of OVX group(14.77±3.12)and maximum load number(11.57±3.18),and the difference was statistically significant(P<0.05).Compared with the OVX group,the serum OCN and PINP indicators of bone formation in the ALN group were increased,while the bone resorption indicators TRACP-5b and CTX-I were decreased,with statistical significance(P<0.05).Conclusion:Alendronate sodium improves bone quality by increasing bone density,improving bone microstructure,increasing bone strength,promoting bone formation and inhibiting bone resorption,without obvious toxic and side effects on organs.

Evolution of human kidney allograft pathology diagnostics through 30 years of the Banff classification process

The second half of the previous century witnessed a tremendous rise in the number of clinical kidney transplants worldwide.This activity was,however,accompanied by many issues and challenges.An accurate diagnosis and appropriate management of causes of graft dysfunction were and still are,a big challenge.Kidney allograft biopsy played a vital role in addressing the above challenge.However,its interpretation was not standardized for many years until,in 1991,the Banff process was started to fill this void.Thereafter,regular Banff meetings took place every 2 years for the past 30 years.Marked changes have taken place in the interpretation of kidney allograft biopsies,diagnosis,and classification of rejection and other non-rejection pathologies from the original Banff 93 classification.This review attempts to summarize those changes for increasing the awareness and understanding of kidney allograft pathology through the eyes of the Banff process.It will interest the transplant surgeons,physicians,pathologists,and allied professionals associated with the care of kidney transplant patients.

Collision tumor of primary malignant lymphoma and adenocarcinoma in the colon diagnosed by molecular pathology:A case report and literature review

BACKGROUND Collision tumors of primary malignant lymphoma and adenocarcinoma in the colon are rare.Primary diffuse large B-cell lymphoma(DLBCL)–adenocarcinoma collision tumors are especially rare.CASE SUMMARY A 74-year-old woman presented with abdominal pain of 1 mo duration.Biopsy under colonoscopy revealed adenocarcinoma of the ascending colon.Subsequently,the patient underwent laparoscopic radical resection of right colon cancer with lymph node dissection.A collision tumor was found incidentally through postoperative pathological sampling.Genetic analysis showed a collision tumor of DLBCL with germinal center B-cell subtype and TP53 mutation,and adenocarcinoma arising in a tubulovillous adenoma in the colon,with BRAF mutation and mutL homolog 1 promoter methylation.The patient died 3 mo after surgery.To our knowledge,this is the 23rd reported case of collision tumor of colorectal adenocarcinoma and lymphoma.The mean age of the 23 patients was 73 years.The most common site was the cecum.There were 15 cases with followup data including 11 living and four dead with a 3-year overall survival rate of 71.5%.CONCLUSION Based on pathological and genetic analysis,surgery combined with chemotherapy or chemoradiotherapy may have good therapeutic effects for collision tumor.

Transitioning of renal transplant pathology from allograft to xenograft and tissue engineering pathology:Are we prepared?

Currently,the most feasible and widely practiced option for patients with endstage organ failure is the transplantation of part of or whole organs,either from deceased or living donors.However,organ shortage has posed and is still posing a big challenge in this field.Newer options being explored are xenografts and engineered/bioengineered tissues/organs.Already small steps have been taken in this direction and sooner or later,these will become a norm in this field.However,these developments will pose different challenges for the diagnosis and management of problems as compared with traditional allografts.The approach to pathologic diagnosis of dysfunction in these settings will likely be significantly different.Thus,there is a need to increase awareness and prepare transplant diagnosticians to meet this future challenge in the field of xenotransplantation/regenerative medicine.This review will focus on the current status of transplant pathology and how it will be changed in the future with the emerging scenario of routine xenotransplantation.

Preliminary Exploration of All-English Teaching in Pathology for International Students

With the development of medical education in China, the education of international students has gradually become an important part of China’s higher education. Pathology is a bridge course connecting basic medicine and clinical medicine, and is a compulsory course for international medical students. In order to improve the quality of all-English teaching in pathology, according to the characteristics of international students and the discipline characteristics of pathology, this paper discussed the problems existing in the pathology teaching of international students, such as language communication, teacher training, textbook selection, teaching content arrangement, etc., aiming at exploring ways to solve these problems and improve the learning effect of international students from teaching practice.

Investigating the Influence of Glaucoma on the Quality of Life among Adult Patients

Background: Research exploring the influence of glaucoma on quality of life has gained momentum in recent years. Numerous studies have investigated the multifaceted aspects of quality of life in glaucoma patients, utilizing various assessment tools and methodologies. Objective: To determine the influence that glaucoma has on the quality of life among adult patients. Study site: kitwe teaching eye hospital, Zambia. Method: It was a cross-sectional study that was conducted from 30th June 2022 to 17th April 2023. The study included 106 diagnosed glaucoma patients who were above the age of 55 years. Data was collected using validated 25-item national eye institute visual function Questionnaire (NEI VFQ-25). The data was analyzed using SPSS version 26 and Microsoft excel to present frequencies and percentages that generated graphical presentation. Results: 62% of the participants worry about their eye sight most of the time, 26% sometimes and 12% a little time. 9% of the participants had little difficulty to read ordinary prints, 14% moderate difficulties and 58% extremely difficult. 40% of the participants could drive despite glaucoma damaging their eyes while 60% could not. Majority of the patients said it was difficult noticing things around them while walking or sitted in one place. There was a significant difference between effects of glaucoma on patients and the existing relationship between glaucoma and quality of life (ANOVA, p = 0.019 and ANOVA, p = 0.023). Conclusion: This study has demonstrated the magnitude of impact that glaucoma has on the Quality of Life (QoL) in diagnosed patients and the relationship between glaucoma and the Quality of Life. Due to the progressive visual loss, the amount of activities these patients would perform is negatively affected especially where social and economic activities are concerned which also affects their monthly earnings for those living in middle to low-income countries. Therefore, social welfare and psycho-social institutions need to increase their support for these glaucoma patients.

Glycolysis and glucose metabolism as a target for bioenergetic and neuronal protection in glaucoma

Vision is arguably our most valued sense,yet approximately 340 million people globally suffer blindness or moderate visual impairment,highlighting the need to further develop and advance treatments for ophthalmic diseases.Glaucoma refers to a group of ocular disorders united by a clinically characteristic optic neuropathy with associated retinal ganglion cell loss.

Glaucoma drainage device implantation and cyclophotocoagulation in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty

AIM:To compare the surgical outcomes of glaucoma drainage device implantation(GDI)and trans-scleral neodymium:YAG cyclophotocoagulation(CPC)in the management of refractory glaucoma after Descemetstripping automated endothelial keratoplasty(DSAEK).METHODS:This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery(15 with GDI and 14 with CPC).The main outcome measures were intraocular pressure(IOP),glaucoma surgery success rate(defined as IOP of 6–21 mm Hg without additional anti-glaucoma operation),number of glaucoma medications,endothelial graft status,and best-corrected visual acuity(BCVA).RESULTS:The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries,both for the GDI and CPC groups.Both groups showed significant IOP reduction after glaucoma surgery.The GDI group presented a significantly higher success rate in IOP control than the CPC group(60%vs 21.4%,P=0.03).Both procedures significantly decreased the number of glaucoma medications(P=0.03).Forty percent and 57%of cases in the GDI and the CPC group,respectively,experienced endothelial graft failure during follow-up(P=0.36).Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group.CONCLUSION:Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK.GDI is preferable to CPC in refractory glaucoma cases after DSAEK,as it manifests a significantly higher success rate for IOP control,similar endothelial graft failure rate,and relatively preserves BCVA than CPC.

Two become one:combination of two risk factors in a new glaucoma animal model

Glaucoma is a group of eye diseases characterized by progressive loss of retinal ganglion cells(RGCs)and optic nerve degeneration.During this process,the visual field is reduced,and blindness may ultimately occur.Worldwide,glaucoma is the second leading cause of blindness,with about 80 million people affected.Glaucoma is a multifactorial disease and due to its complexity,the exact pathomechanisms are not fully understood yet.However,different risk factors,such as elevated intraocular pressure(IOP),age,or myopia,have been identified to date(EGS,2021).

Baerveldt glaucoma implant with Supramid© ripcord stent in neovascular glaucoma: a case series

AIM:To report the outcome of Baerveldt glaucoma implant(BGI)with Supramid©ripcord use in neovascular glaucoma(NVG).METHODS:We retrospectively evaluated the surgical outcome of the BGI with Supramid©3/0 ripcord stent in patients with NVG.No tube ligation or venting slits were performed.Supramid was removed after 3mo if the target intraocular pressure(IOP)was not achieved.Surgical success was defined as IOP≤21 mm Hg with(qualified success)or without IOP-lowering medications(complete success).RESULTS:Twenty-six eyes from 24 patients were included in the study.The median duration of follow-up was 4[interquartile range(IQR)=1-5]y,ranging from 0.5 to 5y.IOP decreased by a mean of 24.2 mm Hg(59.7%);from a mean of 40.5±12.6 mm Hg at baseline to 16.3±11.9 mm Hg,P≤0.001.The number of glaucoma medications reduced from a median of 5(IQR=5-6)to 1(IQR=0-2,P≤0.001)at the final follow-up.Overall success rates were 88.0%at 1y,34.8%at 3y,66.7%at 4y,and 50%at 5y.Hypertensive phase(HP)in the first 3mo occurred in 15/26 eyes(57.7%)with a mean IOP of 31.1 mm Hg.CONCLUSION:BGI with Supramid©ripcord stent gives close to 90%of the overall survival rate at the final follow-up without significant early hypotony.However,early HP is still a challenge.

Monogenic gene therapy for glaucoma and optic nerve injury

The prevalence of glaucoma, the second leading cause of global blindness, is increasing due to aging populations. In glaucoma, degeneration of the optic nerve and retinal ganglion cells(RGCs) causes visual field defects and eventual blindness.

Penetrating canaloplasty in corticosteroid-induced glaucoma:a report of two cases

Dear Editor,We have treated two patients of glucocorticoid-induced glaucoma with penetrating canaloplasty(PCP)since 2021.PCP is a new type internal drainage surgery for glaucoma,which is a bleb-independent filtering surgery combined canaloplasty with trabeculectomy,and the surgery shows a great efficacy of intraocular pressure(IOP)reduction with no surgical complication.PCP surgery started with a fornix-based conjunctival flap and double scleral flap,and Schlemm’s canal was opened,a 10-0 prolene suture was positioned and tensioned within Schlemm’s canal,trabucular meshwork segment was excised and peripheral iridectomy was performed,the scleral flap and the conjunctival flap were closed watertight with 10-0 prolene sutures.

Iridoschisis misdiagnosed as acute angle-closure glaucoma:a case report and literature review

We present the case of a patient with iridoschisis complicated with cataract,peripheral anterior synechiae(PAS),secondary glaucoma,and corneal endothelial damage.The patient was initially misdiagnosed with acute angle-closure glaucoma.Iridoschisis is a rare condition characterized by the splitting of the iris into two layers:the anterior layer breaks down into fibers,floating freely in the anterior chamber with a“shredded wheat”appearance.

Self-assembly of tau fragments as a key pathologic event in tauopathies

Tau protein is encoded by the microtubuleassociated protein tau(MAPT)gene and stabilizes microtubules in the neurons.Tau has unique biophysical properties that make it both highly water-soluble and positively charged.Although tau is an intrinsically disordered protein lacking defined secondary structures,it can acquire highly organized-sheet structures and stack into a filamentous inclusion such as a paired helical filament(PHF).

Ocular decompression retinopathy after phacoemulsification in a patient with primary acute angleclosure glaucoma undergoing chemotherapy

Dear Editor,Ocular decompression retinopathy(ODR),which manifests as diffuse retinal hemorrhage occurring abruptly in multiple locations,including the subretinal,intraretinal,and preretinal spaces,is a rare complication after glaucoma surgery and is caused by sudden,iatrogenic lowering of intraocular pressure(IOP).Implicated procedures include glaucoma drainage implantation,trabeculectomy,iridotomy,and even cataract surgery[1].One report described a case of ocular decompression management following uncomplicated cataract surgery with no posterior capsular rupture or other intraoperative complications[2].Here,we report a rare case of ODR triggered by phacoemulsification and the use of systemic chemotherapeutic drugs in a patient with primary acute angleclosure glaucoma(PACG).The case not only improves our understanding of potential side effects of chemotherapeutic drugs on ophthalmic surgery but may also serve as a reference for clinicians in the management of patients with glaucoma with similar medical histories.