Chemoradiotherapy plus tislelizumab for mismatch repair proficient rectal cancer with supraclavicular lymph node metastasis:A case report

BACKGROUND According to the latest report,colorectal cancer is still one of the most prevalent cancers,with the third highest incidence and mortality worldwide.Treatment of advanced rectal cancer with distant metastases is usually unsatisfactory,especially for mismatch repair proficient(pMMR)rectal cancer,which leads to poor prognosis and recurrence.CASE SUMMARY We report a case of a pMMR rectal adenocarcinoma with metastases of multiple lymph nodes,including the left supraclavicular lymph node,before treatment in a 70-year-old man.He received full courses of chemoradiotherapy(CRT)followed by 4 cycles of programmed death 1 inhibitor Tislelizumab,and a pathologic complete response(pCR)was achieved,and the lesion of the left supraclavicular lymph node also disappeared.CONCLUSION pMMR advanced rectal cancer with preserved intact distant metastatic lymph nodes may benefit from full-course CRT combined with immunotherapy.

Dapagliflozin and sacubitril on myocardial microperfusion in patients with post-acute myocardial infarction heart failure and type 2 diabetes

BACKGROUND Coronary heart disease and type 2 diabetes mellitus(T2DM)frequently coexist,creating a complex and challenging clinical scenario,particularly when complicated with acute myocardial infarction(AMI).AIM To examine the effects of dapagliflozin combined with sakubactrovalsartan sodium tablets on myocardial microperfusion.METHODS In total,98 patients were categorized into control(n=47)and observation(n=51)groups.The control group received noxital,while the observation group was treated with dapagliflozin combined with noxital for 6 months.Changes in myocardial microperfusion,blood glucose level,cardiac function,N-terminal prohormone of brain natriuretic peptide(NT-proBNP)level,growth differentiation factor-15(GDF-15)level,and other related factors were compared between the two groups.Additionally,the incidence of major adverse cardiovascular events(MACE)and adverse reactions were calculated.RESULTS After treatment,in the observation and control groups,the corrected thrombolysis in myocardial infarction frame counts were 37.12±5.02 and 48.23±4.66,respectively.The NT-proBNP levels were 1502.65±255.87 and 2015.23±286.31 pg/mL,the N-terminal pro-atrial natriuretic peptide(NT-proANP)levels were 1415.69±213.05 and 1875.52±241.02 ng/mL,the GDF-15 levels were 0.87±0.43 and 1.21±0.56 g/L,and the high-sensitivity C-reactive protein(hs-CRP)levels were 6.54±1.56 and 8.77±1.94 mg/L,respectively,with statistically significant differences(P<0.05).The cumulative incidence of MACEs in the observation group was significantly lower than that in the control group(P<0.05).The incidence of adverse reactions was 13.73%(7/51)in the observation group and 10.64%(5/47)in the control group,with no statistically significant difference(P>0.05).CONCLUSION Dapagliflozin combined with nocinto can improve myocardial microperfusion and left ventricular remodeling and reduce MACE incidence in patients with post-AMI heart failure and T2DM.The underlying mechanism may be related to the reduction in the expression levels of NT-proANP,GDF-15,and hs-CRP.

Multiple pulp stones emerge across all teeth during mixed dentition:A case report

BACKGROUND This paper reports a rare presentation of multiple pulp stones(PSs)emerging in all teeth during mixed dentition.It offers valuable insights into the clinical diagnosis,treatment,and prognosis of multiple PSs,shedding light on their occurrence during the mixed dentition period.CASE SUMMARY A 10-year-old girl presented with repeated pain in the mandibular right posterior teeth.Intraoral examination revealed carious lesions,abnormal tooth shapes,and anomalies in tooth number.Radiographic examinations showed multiple PSs with diverse shapes,sizes,and quantities in all teeth,alongside anomalies in tooth shape and number.Root canal therapy was initiated,but the patient initially lacked timely follow-up.Upon return for treatment completion,an extracted tooth revealed irregular calculus within the pulp cavity.CONCLUSION This case underscores the importance of considering multiple PSs in mixed dentition,necessitating comprehensive evaluation and management strategies.

His bundle pacing versus left bundle branch pacing on ventricular function in atrial fibrillation patients referred for pacing:a prospective crossover comparison

BACKGROUND His bundle pacing(HBP)and left bundle branch pacing(LBBP)both provide physiologic pacing which maintain left ventricular synchrony.They both improve heart failure(HF)symptoms in atrial fibrillation(AF)patients.We aimed to assess the intra-patient comparison of ventricular function and remodeling as well as leads parameters corresponding to two pacing modalities in AF patients referred for pacing in intermediate term.METHODS Uncontrolled tachycardia AF patients with both leads implantation successfully were randomized to either modality.Echocardiographic measurements,New York Heart Association(NYHA)classification,quality-of-life assessments and leads parameters were obtained at baseline and at each 6-month follow up.Left ventricular function including the left ventricular endosystolic volume(LVESV),left ventricular ejection fraction(LVEF)and right ventricular(RV)function quantified by tricuspid annular plane systolic excursion(TAPSE)were all assessed.RESULTS Consecutively twenty-eight patients implanted with both HBP and LBBP leads successfully were enrolled(69.1±8.1 years,53.6% male,LVEF 59.2%±13.7%).The LVESV was improved by both pacing modalities in all patients(n=23)and the LVEF was improved in patients with baseline LVEF at less than 50%(n=6).The TAPSE was improved by HBP but not LBBP(n=23).CONCLUSION In this crossover comparison between HBP and LBBP,LBBP was found to have an equivalent effect on LV function and remodeling but better and more stable parameters in AF patients with uncontrolled ventricular rates referred for atrioventricular node(AVN)ablation.HBP could be preferred in patients with reduced TAPSE at baseline rather than LBBP.

Gastric adenosquamous carcinoma with an elevated serum level of alpha-fetoprotein:A case report

BACKGROUND Gastric adenosquamous carcinoma(ASC)is rare and characterized by coexisting of adenocarcinoma andsquamous carcinoma within the same tumor.We present a female patient with gastric ASC who had an elevated serum level of alpha-fetopro-tein(AFP),which decreased to normal levels after a laparoscopic distant radical gastrectomy in a short period.The clinicopathological features in AFP-producing gastric cancer(GC)are discussed,as well as potentially available prognostic predi-ctors.CASE SUMMARY A 50-year-old woman presented to our department with a chief complain of a 6-mo history of bloating.She had no basic diseases including heart diseases and respiratory diseases,and she also denied any prior history of dysphagia,hematemesis,melena,rectal bleeding,hematochezia,or unintentional weight loss.Based on her symptoms,an esophagogastroduodenoscopy was performed,showing an annular cavity lesion 3 cm from the pylorus with a diameter of 6 cm.A biopsy of the lesion showed gastric ASC,whereas the pylorus biopsy showed normal mucosa.The patient further received an enhanced computed tomography scan which demonstrated an invasive lesion close to the pylorus with a still clear margin of the tumor to peripheral organs such as the pancreas and liver.Scattered lymph nodes were visible around,whereas no sign of liver metastasis was discovered.Serum tumor markers including carcinoembryonic antigen(CEA),cancer antigen 199(CA199),CA724,CA125,and CA242 were all normal,while the level of serum AFP increased to 172 ng/mL.A laparoscopic distant radical gastrectomy was performed after exclusion of surgical contraindications.Postoperative pathology results showed that the tumor displayed an ulcerated ASC phenotype(90%of medium to highly-differentiated squamous cell carcinoma,10%of poorly differentiated adenocarcinoma.Surprisingly,the serum level of AFP decreased to normal level on post operation day 5.The tumor cells were positive for CK5/6,p63,and CEA,and negative for AFP and Epstein-Barr encoding region.CONCLUSION We presented a rare case of gastric ASC with elevated serum AFP level,which may be new subtype of AFP-producing GC.Follow-up detection of serum AFP might be a useful tool to predict patient prognosis.

Role of MR-DWI and MR-PWI in the radiotherapy of implanted pulmonary VX-2 carcinoma in rabbits

Objective： To detect the activity of tumor cells and tumor blood flow before and after the radiotherapy of implanted pulmonary VX-2 carcinoma in rabbit models by using magnetic resonance diffusion-weighted imaging（MR-DWI） and magnetic resonance perfusion weighted imaging（MR-PWI）, and to evaluate the effectiveness and safety of the radiotherapy based on the changes in the MR-DWI and MR-PWI parameters at different treatment stages.Methods： A total of 56 rabbit models with implanted pulmonary VX-2 carcinoma were established, and then equally divided into treatment group and control group. MR-DWI and MR-PWI were separately performed using a Philips Acheiva 1.5T MRI machine（Philips, Netherland）. MRI image processing was performed using special perfusion software and the WORKSPACE advanced workstation for MRI. MRDWI was applied for the observation of tumor signals and the measurement of apparent diffusion coefficient（ADC） values; whereas MR-PWI was used for the measurement of wash in rate（WIR）, wash out rate（WOR）, and maximum enhancement rate（MER）. The radiation treatment was performed using Siemens PRIMUS linear accelerator. In the treatment group, the radiotherapy was performed 21 days later on a once weekly dosage of 1,000 c Gy to yield a total dosage of 5,000 c Gy.Results： The ADC parameters in the region of interest on DWI were as follows： on the treatment day for the implanted pulmonary VX-2 carcinoma, the t values at the center and the edge of the lesions were 1.352 and 1.461 in the treatment group and control group（P〉0.05）. During weeks 0-1 after treatment, the t values at the center and the edge of the lesions were 1.336 and 1.137（P〉0.05）. During weeks 1-2, the t values were 1.731 and 1.736（P〈0.05）. During weeks 2-3, the t values were 1.742 and 1.749（P〈0.05）. During weeks 3-4, the t values were 2.050 and 2.127（P〈0.05）. During weeks 4-5, the t values were 2.764 and 2.985（P〈0.05）. The ADC values in the treatment group were significantly higher than in the control group. After the radiotherapy（5,000 c Gy）, the tumors remarkably shrank, along with low signal on DWI, decreased signal on ADC map, and remarkably increased ADC values. As shown on PWI, on the treatment day for the implanted pulmonary VX-2 carcinoma, the t values of the WIR, WOR, and MER at the center of the lesions were 1.05, 1.31, and 1.33 in the treatment group and control group（P〉0.05）; in addition, the t values of the WIR, WOR, and MER at the edge of the lesions were 1.35, 1.07, and 1.51（P〉0.05）. During weeks 0-1 after treatment, the t values of the WIR, WOR, and MER at the center of the lesions were 1.821, 1.856, and 1.931（P〈0.05）; in addition, the t values of the WIR, WOR, and MER at the edge of the lesions were 1.799, 2.016, and 2.137（P〈0.05）. During weeks 1-1 after treatment, the t values of the WIR, WOR, and MER at the center of the lesions were 2.574, 2.156, and 2.059（P〈0.05） and the t values of the WIR, WOR, and MER at the edge of the lesions were 1.869, 2.058, and 2.057（P〈0.05）. During weeks 2-3 after treatment, the t values of the WIR, WOR, and MER at the center of the lesions were 2.461, 2.098, and 2.739（P〈0.05） and the t values of the WIR, WOR, and MER at the edge of the lesions were 2.951, 2.625, and 2.154（P〈0.05）. During weeks 3-4 after treatment, the t values of the WIR, WOR, and MER at the center of the lesions were 2.584, 2.107, and 2.869（P〈0.05） and the t values of the WIR, WOR, and MER at the edge of the lesions were 2.057, 2.637, and 2.951（P〈0.05）. During weeks 4-5 after treatment, the t values of the WIR, WOR, and MER at the center of the lesions were 2.894, 2.827, and 3.285（P〈0.05） and the t values of the WIR, WOR, andMER at the edge of the lesions were 3.45, 3.246, and 3.614（P〈0.05）. After the radiotherapy（500 c Gy）, the tumors shrank on the T1 WI, WIR, WOR, and MER; meanwhile, the PWI parameter gradually decreased and reached its minimum value.Conclusions： MR-DWI and MR-PWI can accurately and directly reflect the inactivation of tumor cells and the tumor hemodynamics in rabbit models with implanted pulmonary VX-2 carcinoma, and thus provide theoretical evidences for judging the clinical effectiveness of radiotherapy for the squamous cell carcinoma of the lung.

微创血肿清除术对老年高血压脑出血患者并发症及生活质量的影响

目的:探讨微创血肿清除术对老年高血压脑出血(HICH)患者并发症及生活质量的影响。方法:选取2019年7月至2021年2月期间在阳春市人民医院诊断为HICH的60例老年患者,随机分为两组,对照组30例,应用开颅血肿清除术;观察组30例,应用微创血肿清除术。评价指标为日常生活能力量表(ADL)评分及并发症发生率、手术总有效率。结果:观察组患者术后3个月和6个月ADL评分均高于对照组,而并发症发生率低于对照组(10.00 % vs 33.33 %),差异均具有统计学意义(P<0.05)。观察组患者手术总有效率(96.67 %)明显高于对照组(73.33 %),差异具有统计学意义(P<0.05)。观察组患者血肿清除率高于对照组(90.00 % vs 53.33 %),差异具有统计学意义(P<0.05)。结论:微创血肿清除术可提高老年HICH患者的生活质量,减少并发症发生。

Compound heterozygous mutation of MUSK causing fetal akinesia deformation sequence syndrome: A case report

BACKGROUND Fetal akinesia deformation sequence(FADS)is a broad spectrum disorder with absent fetal movements as the unifying feature.The etiology of FADS is heterogeneous and mostly still unknown.A prenatal diagnosis of FADS relies on clinical features obtained by ultrasound and fetal muscle pathology.However,the recent advances of next-generation sequencing(NGS)can effectively provide a definitive molecular diagnosis.CASE SUMMARY A fetus presented after 24 wk and 6 d of gestation with absent fetal movements and multiple abnormal ultrasonographic signs.The mother had had a previous abortion due to a similarly affected fetus a year before.A clinical diagnosis of FADS was made.The parents refused cord blood examination and chose abortion.A molecular diagnosis of fetal muscle using NGS of genes found a compound heterozygous mutation in the MUSK gene:c.220C>T(chr9:113449410 p.R74W)and c.421delC(chr9:113457745 p.P141fs).CONCLUSION To our knowledge,this is the first report in China showing that a mutation in MUSK is associated with FADS.This supports previous finding that a lethal mutation of MUSK will cause FADS.A precise molecular diagnosis for genetic counseling and options for a prenatal diagnosis of FADS are very important,especially for recurrent FADS;this may also provide evidence for both prenatal and preimplantation genetic diagnoses.

Global Profiling of the Lysine Crotonylome in Different Pluripotent States

Pluripotent stem cells(PSCs)can be expanded in vitro in different culture conditions,resulting in a spectrum of cell states with distinct properties.Understanding how PSCs transition from one state to another,ultimately leading to lineage-specific differentiation,is important for developmental biology and regenerative medicine.Although there is significant information regarding gene expression changes controlling these transitions,less is known about post-translational modifications of proteins.Protein crotonylation is a newly discovered post-translational modification where lysine residues are modified with a crotonyl group.Here,we employed affinity purification of crotonylated(LC–MS/MS)to systematically profile protein crotonylation in mouse PSCs in different states including ground,metastable,and primed states,as well as metastable PSCs undergoing early pluripotency exit.We successfully identified 3628 high-confidence crotonylated sites in 1426 proteins.These crotonylated proteins are enriched for factors involved in functions/processes related to pluripotency such as RNA biogenesis,central carbon metabolism,and proteasome function.Moreover,we found that increasing the cellular levels of crotonyl-coenzyme A(crotonyl-CoA)through crotonic acid treatment promotes proteasome activity in metastable PSCs and delays their differentiation,consistent with previous observations showing that enhanced proteasome activity helps to sustain pluripotency.Our atlas of protein crotonylation will be valuable for further studies of pluripotency regulation and may also provide insights into the role of metabolism in other cell fate transitions.

Cloning and structural characterization of juvenile hormone diol kinase in Spodoptera litura

Juvenile hormone （JH） is one of the key insect hormones that regulate metamorphosis. Juvenile hormone diol kinase （JHDK） is an enzyme involved in JH metabolism and catalyzes JH diol to form a polar end product, JH diol phosphate that has no JH activity. In this study, a JHDK complementary DNA （cDNA） was cloned from Spodoptera litura and the structure and expression of the gene was characterized. The cDNA was 714 base pairs in length and encoded a protein of 183 amino acids with a molecular mass of 21 kDa and an isoelectric point of 4.55. Based on the structure, three putative calcium binding motifs and guanosine triphosphate-binding motifs were predicted in the protein. Modeling of the 3-D structure showed that the protein consisted of eight α-helixes linked with loops, with no β-sheets. The gene was expressed in the epidermis, fat body and midgut of fifth and sixth instar larvae. The expression level in the epidermis was lower than in the fat body and midgut. The gene was expressed at higher levels at the early stages than in the later stages of fifth and sixth instar midgut and fat body. The results suggest that this gene may be involved in the regulation of the JH titer in larvae ofS. litura.

Intricacies in the cross talk between metabolic enzymes,RNA,and protein translation

The development of tech niq ues allowing the systematic capture of the RNA-bound proteome has yielded many surprises.Among these,metabolic enzymes have been frequently detected as RNA-binding proteins(RBPs)by different profiling methodologies in various cell types(Hentze et al.,2018).Compared to previous-more simplistic-views,it is now known that cellular metabolism(not only limited to the tricarboxylic acid,TCA,cycle)is compartmentalized.In fact,metabolic enzymes translocate to the nucleus and are enriched at actively transcribed loci,where they sustain epigenetic/epitranscriptomic marks through localized metabolite production(Mews et al.,2017).It has been proposed that the in teraction with nascent RNAs facilitates the anchorage of metabolic enzymes at target loci(Bao et al.,2018),and it is plausible that mature RNAs work in the same way to assist metabolic reactions in the cytoplasm.