The Method of Combining Internal and External Treatment of Ulcerative Colitis in Chinese Medicine

Traditional Chinese medicine(TCM)believes that the main pathogenesis of ulcerative colitis is spleen deficiency;damp heat in the large intestine as the symptom,the treatment must be warming,clearing,eliminating,tonifying,astringing concurrently.From the concept of combining holism and the local treatment in TCM,idea of combining internal and external treatment is adopted.That is,the external treatment follows the therapeutic principle of using herbs with a bitter and cold nature to eliminate stagnation,and the seven carbon decoction,which can clear heat and dampness,cool the blood,and stop dysentery,is used as a rectal drip to retain the enema.Internal treatment follows the therapeutic principle of warmly tonifying and cultivating vital qi,with oral Chinese herbal medicine named Maodie Tang to strengthen the spleen and tonify the kidney,clearing heat and inducing dampness.

Synthesis and Antitumor Activity of 3-[2-(4-Hydroxy-Phenyl)-Ethyl]-Benzo[d] Isoxazole-4,6-Diol

A new phloretin derivative 1 3-[2-(4-hydroxy-phenyl)-ethyl]-benzo[d] isoxazole-4,6-diol (yield 63%) was synthesized from phloretin by carbonyl nucleophilic addition condensation reaction. Its structure was characterized by 1H NMR, 13C NMR and HR-MS. The phloretin, compound 1, resveratrol and acetylated resveratrol were determined by comparing them with paclitaxel. Anti-tumor activity of alcohol on SPC-A1, EC109, A549, MCF-7 and MDA-MB-231 cell lines. Compound 1 showed better antitumor activity than docetaxel against A549 tumor cells.

社区衰弱和肌少症老年人膳食营养干预的障碍和促进因素:质性 研究的meta整合

目的随着老龄化社会进程加速,老年人躯体衰弱和肌少症的患病率逐年上升,并带来诸多不良影响。膳食营养是防治躯体衰弱和肌少症的重要方式,但在社区环境中实施膳食营养干预受到诸多复杂因素影响。本综述旨在对相关研究中的促进和障碍因素进行系统综述,为制订相关健康管理方案提供参考。方法在Pub Med. .Web of Science 、Medline(Ovid). Embase(Ovid)和Cochrane Library 数据库进行检索,发表时间限定为建库至2023年1月。使用主题词和自由词组合完成检索。使用英国牛津大学循证医学中心质性研究质量评价工具(the Critical Appraisal Skills Program Qualiative Sudies Checklist)对 纳入研究进行质量评价。利用社会生态建模框架对提取的信息进行编码和分析。本综述方案已在PROSPERO注册(CRD42022381339)。结果共纳入10项研究。其中,4项研究仅进行营养相关干预,而膳食营养和运动干预相结合的有6项。根据社会生态模型,从个体特征、外部环境和干预措施3个层面对促进和障碍因素进行了总结,包含10个副主题。结论对社区中的躯体衰弱和肌少症老年人实施膳食营养干预措施时,应整合个人内部动机和外部支持,为参与者制订“量身定制”的干预方案,并最大程度地优化可利用的人力和物理资源。

Necroptosis in inflammatory bowel disease and other intestinal diseases

For a long time, it was believed that apoptosis and necrosis were the main pathways for cell death, but a growing body of research has shown that there are other pathways. Among these, necroptosis, a regulatory caspase-independent, programmed cell death pathway, is supposed to be of importance in the pathogenesis of many diseases. The mechanism of regulating, inducing and blocking necroptosis is a complex process that involves expression and regulation of a series of molecules including receptor interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase like protein. By blocking or downregulating expression of key molecules in the necroptotic pathway, intestinal inflammation can be affected to some extent. In this paper, we introduce the concept of necroptosis, its main pathway, and its impact on the pathogenesis of inflammatory bowel disease(IBD) and other intestinal diseases, to explore new drug targets for intestinal diseases, including IBD.

Psychological impacts of the COVID-19 epidemic on Chinese people: Exposure, post-traumatic stress symptom, and emotion regulation

Objective:To examine the effects of coronavirus disease-2019(COVID-19)exposure,expressive suppression/cognitive reappraisal,and demographic variables on post-traumatic stress symptoms(PTS)among Chinese.Methods:Participants were recruited by social media through We Chat and 6049 Chinese(aged from 17 to 63 years;median=24)from 31 provinces were included in the study.PTS symptoms,expressive suppression,and cognitive reappraisal were assessed after the outbreak of COVID-19.A regression mixture analysis was conducted in Mplus 7.Results:A regression mixture model identified three latent classes that were primarily distinguished by differential effects of COVID-19 exposures on PTS symptoms:(1)Class 1(mildly PTS symptoms,80.9%),(2)Class 2(moderate PTS symptoms,13.0%),and(3)Class 3(high PTS symptoms,6.1%).The results demonstrated that the young,women and people with responsibilities and concerns for others were more vulnerable to PTS symptoms;and they had more expression inhibition and less cognitive reappraisal in three latent classes.Conclusions:The findings suggest that more attention needs to be paid to vulnerable groups such as the young,women and people with responsibilities and concerns for others.Therapies to encourage emotional expression and increase cognitive reappraisal may also be helpful for trauma survivors.

A multi-center,open-label,randomized,parallel-controlled phase II study comparing pharmacokinetic,pharmacodynamics and safety of ripertamab(SCT400)to rituximab(Mab Thera?)in patients with CD20-positive B-cell non-Hodgkin lymphoma

Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclonal antibody,to rituximab(MabThera^(■))in patients with CD20-positive B-cell non-Hodgkin lymphoma(NHL).Methods:Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab(375mg/m^(2))or rituximab(MabThera^(■),375 mg/m^(2)).PK was evaluated using area under the concentration-time curve(AUC)from time 0 to d 85(AUC_(0-85d)),AUC from time 0 to week 1(AUC0-1 w),AUC from time 0 to week 2(AUC_(0-2 w)),AUC from time 0 to week 3(AUC_(0-3 w)),AUC from time 0 to week 8(AUC_(0-8 w)),maximum serum concentration(C_(max)),terminal half-life(T_(1/2)),time to maximum serum concentration(T_(max))and clearance(CL).Bioequivalence was confirmed if the 90%confidence interval(90%CI)of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%.PD,immunogenicity,and safety were also evaluated.Results:From December 30,2014 to November 24,2015,a total of 84 patients were randomized(ripertamab,n=42;rituximab,n=42)and the PK analysis was performed on 76 patients(ripertamab,n=38;rituximab,n=38).The geometric mean ratios of ripertamab/rituximab for AUC_(0-85d),ATC_(0-inf),and Cmaxwere 96.1%(90%CI:87.6%-105.5%),95.9%(90%CI:86.5%-106.4%)and 97.4%(90%CI:91.6%-103.6%),respectively.All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%.For PD and safety evaluation,there was no statistical difference in peripheral CD 19-positive B-cell counts and CD20-positive B-cell counts at each visit,and no difference in the incidence of anti-drug antibodies was observed between the two groups.The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.Conclusions:In this study,the PK,PD,immunogenicity,and safety profile of ripertamab(SCT400)were similar to rituximab(MabThera^(■))in Chinese patients with CD20-positive B-cell NHL.

Microglia activation in the offspring of prenatal Poly I:C exposed rats:a PET imaging and immunohistochemistry study

Background The well-known <pyrotherapy, of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinflammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic-polyribocytidilicacid(Poly l:C) during pregnancy using 11 C'PK11195 positron emission tomography(PET) and immunohistochemistry.Objective The study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly l:C exposed rats.Methods Offspring of Poly l:C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition(PPI) and latent inhibition(LI) test(including active avoidance conditioning task and passive avoidance conditioning task). Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats.11 C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.Results The treatment group showed hyperlocomotion and deficits in PPI and LI compared with the control group. The treatment group also showed an increased11 C-PK11195 uptake ratio in the prefrontal cortex(f=-3.990, p=0.003) and hippocampus(f=-4.462,p=0.001). The number of activated microglia cells was significantly higher in the treatment group than in the control gro叩(hippocampus: f=8.204, p<0.001; prefrontal:f=6.995, p<0.001). Within the treatment group, there were significant correlations between the behavioural parameters and the activation of microglia as measured by PET and immunohistochemistry.Conclusions The present study demonstrated microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly l:C exposed rats.This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.

Gastrointestinal dysfunction is associated with mortality in severe burn patients:a 10-year retrospective observational study from South China

Background:Data on severe and extensive burns in China are limited,as is data on the prevalence of a range of related gastrointestinal(GI)disorders[such as stress ulcers,delayed defecation,opioid-related bowel immotility,and abdominal compartment syndrome(ACS)].We present a multicentre analysis of coincident GI dysfunction and its effect on burn-related mortality.Methods:This retrospective analysis was conducted on patients with severe[≥20%total burn surface area(TBSA)]and extensive(>50%TBSA or>25%full-thickness TBSA)burns admitted to three university teaching institutions in China between January 1,2011 and December 31,2020.Both 30-and 90-day mortality were assessed by collating demographic data,burn causes,admission TBSA,%full-thickness TBSA,Baux score,Abbreviated Burn Severity Index(ABSI)score,and Sequential Organ Failure Assessment(SOFA)score,shock at admission and the presence of an inhalation injury.GI dysfunction included abdominal distension,nausea/vomiting,diarrhoea/constipation,GI ulcer/haemorrhage,paralytic ileus,feeding intolerance and ACS.Surgeries,length of intensive care unit(ICU)stay,pain control[in morphine milligram equivalents(MME)]and overall length of hospital stay(LOHS)were recorded.Results:We analyzed 328 patients[75.6%male,mean age:(41.6±13.6)years]with a median TBSA of 62.0%(41.0%–80.0%);256(78.0%)patients presented with extensive burns.The 90-day mortality was 23.2%(76/328),with 64(84.2%)of these deaths occurring within 30 d and 25(32.9%)occurring within 7 d.GI dysfunction was experienced by 45.4%of patients and had a significant effect on 90-day mortality[odds ratio(OR)=14.070,95%confidence interval(CI)5.886–38.290,P<0.001].Multivariate analysis showed that GI dysfunction was associated with admission SOFA score and%full-thickness TBSA.Overall,88.2%(67/76)of deceased patients had GI dysfunction[hazard ratio(HR)for death of GI dysfunction=5.951],with a survival advantage for functional disorders(diarrhoea,constipation,or nausea/vomiting)over GI ulcer/haemorrhage(P<0.001).Conclusion:Patients with severe burns have an unfavourable prognosis,as nearly one-fifth died within 90 d.Half of our patients had comorbidities related to GI dysfunction,among which GI ulcers and haemorrhages were independently correlated with 90-day mortality.More attention should be given to severe burn patients with GI dysfunction.

Comparative genomic analysis of Lactobacillus crispatus strains Lc31 and Lc83 with anti-cervical cancer potential by complete genome sequencing

Lactobacillus crispatus is a commonly found species in the urogenital tract(UGT)of healthy females and can also colonize other niches,such as the gastrointestinal tract(GIT).Although its potential protective role in cervical cancer has been reported,the anticancer mechanisms involved are still unclear.In this study,we sequenced and characterized the complete genomes of two L.crispatus strains(Lc31 and Lc83)isolated from the UGT of healthy women of reproductive age.Phylogenetic and phylogenomic analyses of these two strains and 15 other L.crispatus strains with complete genome sequences revealed that strains from the UGT and GIT clustered separately.UGT strains had a larger genome size,higher GC contents,and more protein-coding sequences and insertion sequence(Is)elements,indicating the likelihood of active horizontal gene transfer in this niche.We found a universal presence of genes encoding bacteriocins and the absence of virulence factors and antibiotic resistance genes in UGT strains,suggesting the potential of L.crispatus as a urogenital probiotic.Comparative genomic analysis identified an ula gene cluster responsible for L-ascorbate catabolism exclusively in UGT strains,and carbohydrate fermentation experiments confirmed that this substrate supported the growth of L.crispatus Lc31 and Lc83.Our findings improve the understanding of how the genome determines niche adaptation by L.crispatus,providing a foundation for investigating the mechanisms by which urogenital-derived L.crispatus promotes female health.

Exfoliative esophageal bleeding caused by blind placement of a nasogastric tube:Two cases and a literature review

Transnasal intubation is a clinical operation usually performed blindly at the bedside.Mild adverse events,such as epistaxis and tube misplacement,are relatively common.Esophageal bleeding or perforation and other serious adverse events are rare.In the present study,two cases of severe diffuse esophageal bleeding caused by the blind placement of a nasogastric tube are described.These cases were successfully treated using a covered metal stent or Sengstaken-Blakemore tube.A review of the literature regarding the possible causes of such adverse events and the potential endoscopic treatments for severe hemorrhage are discussed.

Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interferewith 5-HT Signaling Pathway

Objective:To investigate whether electroacupuncture(EA) at sensitized acupoints could reduce sympathetic-sensory coupling(SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine(5-HT)ergic neural pathways to relieve colitis and somatic referred pain,and explore the underlying mechanisms.Methods:Rats were treated with 5% dextran sodium sulfate(DSS) solution for 7 days to establish a colitis model.Twelve rats were randomly divided into the control and model groups according to a random number table(n=6).According to the Research on Rat Acupoint Atlas",sensitized acupoints and non-sensitized acupoints were determined.Rats were randomly divided into the control,model,Zusanli-EA(ST 36),Dachangshu-EA(BL 25),and Xinshu(BL 15) groups(n=6),as well as the control,model,EA,and EA+GR113808(a 5-HT inhibitor)groups(n=6).The rats in the control group received no treatment.Acupuncture was administered on 2 days after modeling using the stimulation pavameters:1 mA,2 Hz,for 30 min,with sparse and dense waves,for 14 consecutive days.GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days.Mechanical sensitivity was assessed with von Frey filaments.Body weight and disease activity index(DAI) scores of rats were determined.Hematoxylin and eosin staining was performed to observe colon histopathology.SSC was analyzed by immunofluorescence staining.Immunohistochemical staining was performed to detect 5-HT and substance P(SP) expressions.The calcitonin gene-related peptide(CGRP) in skin tissue and tyrosine hydroxylase(TH) protein levels in DRG were detected by Western blot.The levels of hyaluronic acid(HA),bradykinin(BK),prostaglandin I2(PGI2) in skin tissue,5-HT,tryptophan hydroxylase 1(TPH1),serotonin transporters(SERT),5-HT 3 receptor(5-HT3R),and 5-HT 4 receptor(5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay(ELISA).Results:BL 25 and ST 36 acupoints were determined as sensitized acupoints,and BL 15 acupoint was used as a non-sensitized acupoint.EA at sensitized acupoints improved the DAI score,increased mechanical withdrawal thresholds,and alleviated colonic pathological damage of rats.EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels(P<0.05).Furthermore,EA at sensitized acupoints reduced BK,PGI2,5-HT,5-HT3R and TPH1 levels,and increased HA,5-HT4R and SERT levels in colitis rats(P<0.05).GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats(P<0.05).Conclusion:EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway,and reducing SSC inflammatory response.

RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells.Relevant studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of therapeutics.As a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular phenotypes.To be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts.In this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied types.Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial metabolism.And we highlight the regulation of RNA modifications on immunometabolism,further influencing immune responses.Above all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted therapeutics.Eventually,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway inflammation.The envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this process.Pathogens could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)signaling.However,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be elucidated.Here,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial barrier.In addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(PDE4D)expression in airway epithelial cells.This elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein.Overall,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

Prealbumin as a prognostic indicator for hospital readmission of ulcerative colitis patients

Dear Editor,Inflammatory bowel diseases(IBD)such as ulcerative colitis(UC)and Crohn's disease are affecting increasing numbers of patients worldwide.1 These chronic diseases significantly impact patients'quality of life as they are incurable and disabling.1 Patients with IBD have had an increasing rate of hospitalizations,half of all UC patients are hospitalized at least once during their lifetime,and readmissions after a UC-related hospitalization are common.

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across species.Wnt proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling pathways.Cellular behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling paths.Wnt signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various tissues.This includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem cells.Wnt signaling has also been implicated in tumor cells that exhibit stem cell-like properties.Wnt signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone disorders.Not surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including cancer.Mutations of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and metastasis.Altogether,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt pathway.Beginning with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

Stem Cell-Based Hair Cell Regeneration and Therapy in the Inner Ear

Hearing loss has become increasingly prevalent and causes considerable disability,thus gravely burdening the global economy.Irreversible loss of hair cells is a main cause of sensorineural hearing loss,and currently,the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids,but these are of limited benefit in patients.It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies.At present,how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research.Multi-ple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells,and in this article,we first review the principal mechanisms underlying hair cell reproduction.We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration,and we summarize current achievements in hair cell regeneration.Lastly,we discuss potential future approaches,such as small molecule drugs and gene therapy,which might be applied for regenerating functional hair cells in the clinic.

Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer(NECTAR):a multi-center phase 2 study

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer(LARC)patients with microsatellite stable(MsS)/mismatch repair-proficient(pMMR)tumors is an attractive,but debatable strategy.This phase 2,multicenter,prospective,single-arm study enrolled patients from 6 centers from June 2021 to November 2022.Locally advanced rectal cancer(LARC,cT_(3-4a)N_(0)M_(0) and cT_(1-4a)N_(1-2)M_(0))patients aged≥18 years with the distance from distal border of tumor to anal verge≤10 cm(identified by Magnetic Resonance Imaging)were qualifed for inclusion.The patients received long-course radiotherapy(50 Gy/25 fractions,2 Gy/fraction,5 days/week)and three 21-day cycles capecitabine(850-1000 mg/m2,bid,po,day1-14)and three 21-day cycles tislelizumab(200 mg,iv.gtt,day8)as neoadjuvant.Total mesorectal excision(TME)was 6-12 weeks after the end of radiotherapy to achieve radical resection.A total of 50 patients were enrolled in this study.The pathological complete response rate was 40.0%[20/50,95%confidence interval(CI):27.61-53.82%],while 15(30.0%,95%CI:19.1-43.75%),9(18.0%,95%CI:9.77-30.8%),2(4.0%,95%CI:1.10-13.46%)patients respectively achieved grade 1,2,and 3 tumor regression.Treatment-related adverse events(TRAEs)occurred in 28(56.0%)LARC patients,including 26(52.0%)with grade I-II and 2(4.0%)with grade II(1 with grade 3 immune-related colitis and 1 with grade 3 rash).PD-1 blockade plus long-course chemoradiotherapy(CRT)showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients.A larger randomized controlled study is desired to further validate the above findings.

Aging-induced YTHDF aggregates impair mitochondrial function by trapping mitochondrial RNAs and suppressing their expression in the brain

DearEditor,Brain aging is associated with a decrease in cognitive function,which is often accompanied by defective changes in mitochondrial morphology and reduction in mitochondrial function(Faitg et al.,2021).The main function of mitochondria is to produce energy in the form of ATP,which is vital to fulfill high energy demand of neurons,mainly for synaptic processes(Lee et al.,2018).Mitochondrial dysfunction acts as a key factor for age-related cognitive decline(Grimm and Eckert,2017).

MPDZ variants associated with epilepsies and/or febrile seizures and the individualized genotype-phenotype correlation

The multiple PDZ domain crumbs cell polarity complex component gene(MPDZ;MIM:603785),is highly expressed in the brain across the whole lifespan.It encodes the multiple PDZ domain protein,which is a member of the NMDAR signaling complex that may play a role in the control of AMPAR potentiation and synaptic plasticity in excitatory synapses."Previously,MPDZ variants have been demonstrated to be associated with autosomal recessive congenital hydrocephalus-2(HYC2;MIM:615219)which is commonly complicated by brain abnormalities and developmental delay.Seizures were reported in only one case.The association between MPDz and epilepsy requires clarification.

Intestinal Microbial Community Differs between Acute Pancreatitis Patients and Healthy Volunteers

A case control study including 45 acute pancreatitis and 44 healthy volunteers was performed to investigate the association between intestinal microbial community and acute pancreatitis. High-throughput 16S r RNA gene amplicon sequencing was used to profile the microbiological composition of the samples. In total, 27 microbial phyla were detected and the samples of pancreatitis patients contained fewer phyla. Samples from acute pancreatitis patients contained more Bacteroidetes and Proteobacteria and fewer Firmicutes and Actinobacteria than those from healthy volunteers. PCo A analyses distinguished the fecal microbial communities of acute pancreatitis patients from those of healthy volunteers. The intestinal microbes of acute pancreatitis patients are different from those of healthy volunteers. Modulation of the intestinal microbiome may serve as an alternative strategy for treating acute pancreatitis.