Temporal and Spatial Distribution of SARS-CoV-2 Aerosols in a Large-Scale Fangcang Shelter Hospital in Shanghai,China

The coronavirus disease 2019(COVID-19)pandemic caused by frequently mutating severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has had a worldwide impact.However,detailed data on the potential aerosol transmission of SARS-CoV-2 in real-world and controlled laboratory settings remain sparse.During the COVID-19 pandemic in Shanghai,China in 2022,samples were collected in a Fangcang shelter hospital,a large-scale temporary hospital rapidly built by converting the existing National Exhibition and Convention Center(Shanghai)into a health care facility.Aerosol samples at different sites and intervals around patients and in public areas,surface samples,and pharyngeal swab samples from corresponding patients were included.Samples were tested for SARS-CoV-2 using real-time quantitative polymerase chain reaction(RT-qPCR)assays,followed by sequencing if the cycle threshold(Ct)value was<30.The positivity rate for SARS-CoV-2 in aerosol samples was high in contaminated zones(37.5%,104/277),especially around the bed(41.2%,68/165)and near ventilation inlets(45.2%,14/31).The prevalence of SARS-CoV-2 around the bed,public areas,and air inlets of exhaust vents fluctuated and was closely related to the positivity rate among patients at corresponding sampling sites.Some surface samples of different personal protective equipment from medical staff had high positivity rates.Sixty sequences of joined ORF1ab and spike genes obtained from sixty samples represented two main clusters of Omicron SARS-CoV-2.There was consistency in virus sequences from the same patient and their environment,and the detected virus sequences matched those of virus strains in circulation during the collection periods,which indicated a high likelihood of cross-contamination in the Fangcang shelter hospital.In summary,the results provide a quantitative and real landscape of the aerosol transmission of SARS-CoV-2 and a patient-centered view of contamination in large and enclosed spaces and offer a useful guide for taking targeted measures to avoid nosocomial infections during the management of SARS-CoV-2 or other respiratory virus diseases in a Fangcang shelter hospital.

Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

Lactate:a prospective target for therapeutic intervention in psychiatric disease

Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde rs.This may be attributed to the limited range of neurotransmitters that are regulated by psychotropic drugs.Recent findings indicate the need for investigation of psychotropic medications that target less-studied neurotransmitte rs.Among these candidate neurotransmitters,lactate is developing from being a waste metabolite to a glial-neuronal signaling molecule in recent years.Previous studies have suggested that cerebral lactate levels change considerably in numerous psychiatric illnesses;animal experiments have also shown that the supply of exogenous la ctate exerts an antidepressant effect.In this review,we have described how medications targeting newer neurotransmitte rs offer promise in psychiatric diseases;we have also summarized the advances in the use of lactate(and its corresponding signaling pathways)as a signaling molecule.In addition,we have described the alterations in brain lactate levels in depression,anxiety,bipolar disorder,and schizophrenia and have indicated the challenges that need to be overcome before brain lactate can be used as a therapeutic target in psychopharmacology.

Photobiomodulation inhibits the expression of chondroitin sulfate proteoglycans after spinal cord injury via the Sox9 pathway

Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.

Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells

The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechanisms responsible for initiating spontaneous ATP release have not been determined.Our previous study revealed that telomerase reverse transcriptase(TERT)is expressed in the basilar membrane during the first postnatal week.Its role in cochlear development remains unclear.In this study,we investigated the expression and role of TERT in postnatal cochlea supporting cells.Our results revealed that in postnatal cochlear Kölliker’s organ supporting cells,TERT shifts from the nucleus into the cytoplasm over time.We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo.Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis,suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions.We observed increased ATP synthesis,release and activation of purine signaling systems in supporting cells during the first 10 postnatal days.The phenomenon that TERT translocation coincided with changes in ATP synthesis,release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system.Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.

Association between the cumulative triglyceride-glucose index and the recurrence of atrial fibrillation after radiofrequency catheter ablation

BACKGROUND Triglyceride-glucose(TyG)index values are a new surrogate marker for insulin resistance.This study aimed to explore the relationship between cumulative TyG index values and atrial fibrillation(AF)recurrence after radiofrequency catheter ablation(RFCA).METHODS A total of 576 patients with AF who underwent RFCA at the Second Affiliated Hospital of Xi'an Jiaotong University were included in this study.The participants were grouped based on cumulative TyG index values tertiles within 3 months after ablation.Cox regression and restricted cubic spline analyses were used to determine the relationship between cumulative TyG index values and AF recurrence.The predictive value of all risk factors was assessed by receiver operating curve analysis.RESULTS There were 375 patients completed the study(age:63.23±10.73 years,64.27%male).The risk of AF recurrence increased with increasing cumulative TyG index values tertiles.After adjusting for potential confounders,patients in the medium cumulative TyG index group[hazard ratio(HR)=4.949,95%CI:1.778–13.778,P=0.002]and the high cumulative TyG index group(HR=8.716,95%CI:3.371–22.536,P<0.001)had a higher risk of AF recurrence than those in the low cumulative TyG index group.The restricted cubic spline regression model also showed an increased risk of AF recurrence with increasing cumulative TyG index values.When considering cumulative TyG index values,left atrial diameter,and lactate dehydrogenase levels as a comprehensive factor,the model could effectively predict AF recurrence after RFCA[area under the curve(AUC)=0.847,95%CI:0.797–0.897,P<0.001].CONCLUSIONS Cumulative TyG index values were a risk factor for AF recurrence after RFCA.Monitoring longitudinal TyG index values may assist with optimized for risk stratification and outcome prediction for AF recurrence.

Clinical features and prognostic factors of duodenal neuroendocrine tumours:A comparative study of ampullary and nonampullary regions

BACKGROUND Duodenal neuroendocrine tumours(DNETs)are rare neoplasms.However,the incidence of DNETs has been increasing in recent years,especially as an incidental finding during endoscopic studies.Regrettably,there is no consensus regarding the ideal treatment of DNETs.Even there are few studies on the clinical features and survival analysis of DNETs.AIM To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine tumours.METHODS The clinical data of DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected.Neuroen-docrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group;neuroendocrine tumours in any part of the duo-denum outside the ampullary area were divided into the nonampullary region group.Using a retrospective study,the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were analysed.RESULTS Twenty-nine DNET patients were screened.The male to female ratio was 1:1.9,and females comprised the majority.The ampullary region group accounted for 24.1%(7/29),while the nonampullary region group accounted for 75.9%(22/29).When diagnosed,the clinical symptoms of the ampullary region group were mainly abdominal pain(85.7%),while those of the nonampullary region groups were mainly abdominal distension(59.1%).There were differences in the composition of staging of tumours between the two groups(Fisher's exact probability method,P=0.001),with nonampullary stage II tumours(68.2%)being the main stage(P<0.05).After the diagnosis of DNETs,the survival rate of the ampullary region group was 14.3%(1/7),which was lower than that of 72.7%(16/22)in the nonampullary region group(Fisher's exact probability method,P=0.011).The survival time of the ampullary region group was shorter than that of the nonampullary region group(P<0.000).The median survival time of the ampullary region group was 10.0 months and that of the nonampullary region group was 451.0 months.Multivariate analysis showed that tumours in the ampulla region and no surgical treatment after diagnosis were independent risk factors for the survival of DNET patients(HR=0.029,95%CI 0.004-0.199,P<0.000;HR=12.609,95%CI:2.889-55.037,P=0.001).Further analysis of nonampullary DNET patients showed that the survival time of patients with a tumour diameter<2 cm was longer than that of patients with a tumour diameter≥2 cm(t=7.243,P=0.048).As of follow-up,6 patients who died of nonampullary DNETs had a tumour diameter that was≥2 cm,and 3 patients in stage IV had liver metastasis.Patients with a tumour diameter<2 cm underwent surgical treatment,and all survived after surgery.CONCLUSION Surgical treatment is a protective factor for prolonging the survival of DNET patients.Compared to DNETs in the ampullary region,patients in the nonampullary region group had a longer survival period.The liver is the organ most susceptible to distant metastasis of nonampullary DNETs.

Circulating cell-free mtDNA as a new biomarker for cancer detection and management

Cancer is a major cause of death worldwide,and was responsible for 19.29 million new cases and 9.96 million deaths in 2020 alone.The total number of patients with cancer worldwide is estimated to reach 28 million by 2040.The American Association for Cancer Research has also estimated approximately 16.2 million cancer deaths by 20401.

Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury:a randomized controlled study

For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer

BACKGROUND Laparoscopic radical gastrectomy is widely used,and perioperative complications have become a highly concerned issue.AIM To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery,guide perioperative treatment strategies for gastric cancer patients,and prevent serious complications.METHODS In total,998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model,and 398 patients were included in the validation group.The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected.Three machine learning methods,lasso regression,random forest,and artificial neural networks,were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy,and their prediction efficacy and accuracy were evaluated.RESULTS The constructed complication model,particularly the random forest model,could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy.It exhibited stable performance in external validation and is worthy of further promotion in more centers.CONCLUSION Using the risk factors identified in multicenter datasets,highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established.We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

Prevalence of minimal hepatic encephalopathy and quality of life evaluations in hospitalized cirrhotic patients in China

AIM:To investigate the prevalence of minimal hepatic encephalopathy(MHE)and to assess corresponding health-related quality of life(HRQoL)in hospitalized cirrhotic patients in China.METHODS:This multi-center cross-sectional study included 16 teaching hospitals,which were members of "Hepatobiliary Cooperation Group,Society of Gastroenterology,Chinese Medical Association",from different areas of China carried out between June and October in 2011.All the eligible hospitalized cirrhotic patients(n = 538)were required to complete triplicate number connection tests combined with one digit symbol test for diagnosing MHE.Patients' clinical examination data were complemented by a modified questionnaire assessing HRQoL.Written informed consent was obtained from each patient.RESULTS:Male was predominant(68.6%)in 519 patients who met the criteria of the study,with a mean age of 49.17 ± 11.02 years.The most common cause of liver cirrhosis was chronic hepatitis B(55.9%).The prevalence of MHE was 39.9% and varied by ChildPugh-Classification score(CPC-A:24.8%,CPC-B:39.4% and CPC-C:56.1%,P < 0.01).MHE(P < 0.01)and higher CPC scores(P < 0.01)were associated with a high HRQoL scores(reflecting poorer quality of life).The prevalence of MHE was proportionate to CPC(P = 0.01)and high quality of life scores(P = 0.01).CONCLUSION:Hospitalized cirrhotic patients have a high prevalence of MHE that is proportionate to the degree of liver function and HRQoL impairment.

Quantitative proteomic and phosphoproteomic analyses of the hippocampus reveal the involvement of NMDAR1 signaling in repetitive mild traumatic brain injury

The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment.This cognitive impairment is thought to result specifically from damage to the hippocampus.In this study,we detected cognitive impairment in mice 6 weeks after repetitive mild traumatic brain injury using the novel object recognition test and the Morris water maze test.Immunofluorescence staining showed that p-tau expression was increased in the hippocampus after repetitive mild traumatic brain injury.Golgi staining showed a significant decrease in the total density of neuronal dendritic spines in the hippocampus,as well as in the density of mature dendritic spines.To investigate the specific molecular mechanisms underlying cognitive impairment due to hippocampal damage,we performed proteomic and phosphoproteomic analyses of the hippocampus with and without repetitive mild traumatic brain injury.The differentially expressed proteins were mainly enriched in inflammation,immunity,and coagulation,suggesting that non-neuronal cells are involved in the pathological changes that occur in the hippocampus in the chronic stage after repetitive mild traumatic brain injury.In contrast,differentially expressed phosphorylated proteins were mainly enriched in pathways related to neuronal function and structure,which is more consistent with neurodegeneration.We identified N-methyl-D-aspartate receptor 1 as a hub molecule involved in the response to repetitive mild traumatic brain injury,and western blotting showed that,while N-methyl-D-aspartate receptor 1 expression was not altered in the hippocampus after repetitive mild traumatic brain injury,its phosphorylation level was significantly increased,which is consistent with the omics results.Administration of GRP78608,an N-methyl-D-aspartate receptor 1 antagonist,to the hippocampus markedly improved repetitive mild traumatic brain injury-induced cognitive impairment.In conclusion,our findings suggest that N-methyl-D-aspartate receptor 1 signaling in the hippocampus is involved in cognitive impairment in the chronic stage after repetitive mild traumatic brain injury and may be a potential target for intervention and treatment.

Long-term outcomes of anti-VEGF treatment with 5+PRN regimen for macular edema due to central retinal vein occlusion

AIM:To assess the long-term outcomes of treating macular edema(ME)associated with central retinal vein occlusion(CRVO)with a regimen of“5+pro re nata(PRN)”.METHODS:This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO(non-iCRVO group,n=15)and ischemic CRVO(iCRVO group,n=12).The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab,followed by reinjections as needed or PRN.Retinal laser photocoagulation or intravitreal dexamethasone implants(DEX)were implemented in both groups when necessary.The best-corrected visual acuity(BCVA,logMAR)and central retinal thickness(CRT)were recorded at baseline,at 1,2,3,4,5,6,and 12mo,and at the final visit.The efficacy rates of BCVA and CRT before and after treatment were calculated.The number of injections at each visit and the incidence of adverse events were also recorded.RESULTS:The patients,aged 59.4±15.1y,were followed up for 24.7±8.8mo(range:15-42mo).After treatment,BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR(P=0.038)at the final visit in all patients.Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points,but there was no statistical significance(P=0.197 and 0.33,respectively).The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups(all P<0.001).The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection,48.15%for BCVA and 62.96% for CRT after 5 consecutive injections,and 74.08% for BCVA and 100% for CRT at the end of follow up.The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups(P>0.05).Laser treatment was applied to all eyes in the iCRVO group,while only 5 patients in the noniCRVO group.Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch.DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group.CONCLUSION:The 5+PRN anti-vascular endothelial growth factor(VEGF)regimen is found to be safe and effective for both iCRVO and non-iCRVO,especially in the iCRVO group.The best regimen for such patients needs to be further investigated.Adjuvant laser therapy and DEX are necessary in some cases.

Long-term efficacy and safety of YAG laser vitreolysis for vision degrading myodesopsia

AIM:To assess the long-term efficacy and safety of yttrium-aluminum garnet(YAG)laser vitreolysis for vision degrading myodesopsia(VDM)caused by posterior vitreous detachment(PVD).METHODS:This retrospective study reviewed VDM patients of PVD type undergoing YAG laser vitreolysis.The baseline demographic information,the patterns of floaters,the number of floaters,and the subjective improvement of floater sympotoms(ranging from 0 to 100%)from medical records were collected.Significant improvement was defined as a relief of floater symptoms of≥50%at the final visit.The long-term efficacy and safety of YAG laser vitreolysis were analyzed.The risk factors linked to significant improvement of floater symptoms were defined using univariate and multivariate logistic regression analyses.RESULTS:The final analysis included 221 patients with VDM.The mean age of patients was 61.08±7.74y,and the mean length of follow-up was 21.38±5.61mo.Totally 57.01%of patients experienced a significant improvement in their floater symptoms after YAG laser therapy,and none of them developed delayed retinal abnormalities such as retinal tears or detachments.Age(OR=1.049,95%CI=1.007-1.092,P=0.021)was identified as a significant risk factor for significant improvement in VDM.CONCLUSION:YAG laser vitreolysis is an effective and secure treatment for PVD-type VDM,and patients of advanced age are more likely to get favorable outcomes.

Syphilitic uveitis in HIV-positive patients: report of a case series, treatment outcomes, and comprehensive review of the literature

AIM:To report the clinical characteristics,treatment and outcomes of active syphilitic uveitis in human immunodeficiency virus(HIV)positive patients and compare them with the previously published data.METHODS:Retrospective analysis of the case series from an infectious disease center in southern China was conducted.Comprehensive review of previously published cases of HIV positive syphilitic uveitis was conducted using the PubMed and Web of Science databases and the references listed in the identified articles.RESULTS:Twelve HIV positive patients with active syphilitic uveitis were collected.All were male,with age of 36.3y(range 27 to 53y).Five(41.7%)had a history of syphilis,and three of them had received anti-syphilis treatment.Ocular manifestations included corneal epithelial defect(13%),complicated cataract(17.4%),vitreous opacity(82.6%),optic disc edema(26.1%),macular edema(30.4%),neuro-retinitis(43.5%),and retinal hemorrhage(26.1%).After standardized syphilitic treatment,intraocular inflammation was reduced and vision improved in all cases.The literature review summarizes 105 previously reported cases of HIV positive syphilitic uveitis.High serum rapid plasma regain(RPR)titers may be associated with severe uveitis and poor vision.Treatment with penicillin,ceftriaxone sodium,or penicillin plus benzylpenicillin instead of using benzylpenicillin alone can significantly improve bestcorrected visual acuity(BCVA)in HIV positive ocular syphilis patients.CONCLUSION:For HIV positive syphilitic uveitis patients,prompt diagnosis and appropriate treatment and follow-up are paramount.In our series,the clinical manifestations are diverse.Syphilis patients treated by penicillin G or long-acting penicillin before may still develop syphilitic uveitis.Patients who relapse after long-term penicillin treatment can still benefit from penicillin G.

Knockdown of NADPH oxidase 4 reduces mitochondrial oxidative stress and neuronal pyroptosis following intracerebral hemorrhage

Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious cycle leading to reactive oxygen species accumulation,resulting in progression of the pathological process.Therefore,breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage.Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4(NADPH oxidase 4,NOX4)led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage.The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress,mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage.We found that NOX4 knockdown by adeno-associated virus(AAV-NOX4)in rats enhanced neuronal tolerance to oxidative stress,enabling them to better resist the oxidative stress caused by intracerebral hemorrhage.Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria,relieved mitochondrial damage,prevented secondary reactive oxygen species accumulation,reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats.Finally,we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4.The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis,which is similar to the effect of AAV-NOX4.This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production,and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.

Aberrant expression of COL4A1 in age-related cataract and its effect on cell proliferation,apoptosis and gene expression changes

AIM:To evaluate the regulation of the aberrant expression of collagen typeⅣalpha 1 chain(COL4A1)in the development of age-related cataract(ARC).METHODS:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and Western blot analysis were employed to evaluate the expression of COL4A1 in ARC patients and healthy controls.The proliferation,apoptosis,cell cycle and epithelial-mesenchymal transition(EMT)of human lens epithelial cell(HLE-B3)were further analyzed under the condition of COL4A1 gene silence.Alteration of gene expression at mRNA level after knockdown COL4A1 were also evaluated by qRT-PCR on HLE-B3 cells.RESULTS:The aberrant expression of COL4A1 was identified a clinically associated with the ARC.Silencing of COL4A1 promoted the apoptosis and inhibited the proliferation of HLE-B3 by blocking the cell cycle.Moreover,COL4A1 gene silence didn’t affect the cytoskeleton of HLE-B3 but down-regulated the Collagen typeⅣAlpha 2 Chain(COL4A2),paired box 6(PAX6),procollagen-lysine 2-oxoglutarate 5-dioxygenases 1(PLOD1)and procollagenlysine 2-oxoglutarate 5-dioxygenases 2(PLOD2)expression levels in HLE-B3 cells.Silencing the COL4A1 gene induced EMT of the HLE-B3 cells by promoting the transforming growth factor beta(TGF-β)expression.CONCLUSION:Silencing of COL4A1 induces S-phase arrest,also inhibits the proliferation and enhance HLE-B3 apoptosis and EMT,and down-regulates the expression of COL4A2,PAX6,PLOD1 and PLOD2.Thus,the expression alteration of COL4A1 may play a critical role in the pathogenesis of ARC.

Potential targets and mechanisms of photobiomodulation for spinal cord injury

As a classic noninvasive physiotherapy,photobiomodulation,also known as low-level laser therapy,is widely used for the treatment of many diseases and has anti-inflammatory and tissue repair effects.Photobiomodulation has been shown to promote spinal cord injury repair.In our previous study,we found that 810 nm low-level laser therapy reduced the M1 polarization of macrophages and promoted motor function recovery.However,the mechanism underlying this inhibitory effect is not clear.In recent years,transcriptome sequencing analysis has played a critical role in elucidating the progression of diseases.Therefore,in this study,we performed M1 polarization on induced mouse bone marrow macrophages and applied low-level laser therapy.Our sequencing results showed the differential gene expression profile of photobiomodulation regulating macrophage polarization.We analyzed these genes using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.Networks of protein-protein interactions and competing RNA endogenous networks were constructed.We found that photobiomodulation inhibited STAT3 expression through increasing the expression of miR-330-5p,and that miR-330-5p binding to STAT3 inhibited STAT3 expression.Inducible nitric oxide synthase showed trends in changes similar to the changes in STAT3 expression.Finally,we treated a mouse model of spinal cord injury using photobiomodulation and confirmed that photobiomodulation reduced inducible nitric oxide synthase and STAT3 expression and promoted motor function recovery in spinal cord injury mice.These findings suggest that STAT3 may be a potential target of photobiomodulation,and the miR-330-5p/STAT3 pathway is a possible mechanism by which photobiomodulation has its biological effects.