[Antibody-drug conjugates combined with immunotherapy: a potential game changer in the treatment of upper tract urothelial carcinoma].

Currently, treatment strategies for upper tract urothelial carcinoma (UTUC) are changing rapidly. However, there are many limitations in the implementation of new surgical methods and systemic treatment options, which cannot reverse the current status quo of UTUC treatment. In recent years, antibody-drug conjugates have shown great potential in the field of cancer treatment, which can activate the immune system and enhance the effect of immunotherapy while accurately killing targeted tumor cells. The results of multiple clinical trials, including the EV-302 study, have confirmed that combination therapy can improve the survival rate of patients with advanced urothelial cancer, and may replace chemotherapy as the first-line treatment for advanced urothelial cancer. However, there are still a series of challenges in the application of combination therapy in UTUC, such as low level of evidence, adverse reactions, and drug resistance. In the future, it is necessary to focus on clinical trials of UTUC combination therapy, further optimize antibody drug conjugates and immunotherapy drugs to adapt to the disease characteristics of UTUC, and further study the molecular biology characteristics of UTUC to meet this series of challenges.

[Soil microorganisms and physicochemical properties in marshlands along the Yangtze River basin at different types of land use and their effects on distribution of Oncomelania hupensis snails].

OBJECTIVE: To investigating the microbial communities and physicochemical properties of soil and distribution of Oncomelania hupensis snails in marshlands along the Yangtze River basin at different types of land use, and to examine the effects of soil microorganisms and physicochemical properties on snail distribution, so as to provide insights into snail control and schistosomiasis prevention in marshland along the Yangtze River basin. METHODS: Marshlands with four types of land use were selected along the Yangtze River basin on April 2021, including poplar forest-crops integrated planting, reed areas, agricultural cultivation lands and ditches. The distribution of snails and physicochemical properties of soil were investigated in marshlands with different types of land use, and the V3 to V4 regions of the bacterial 16S ribosomal RNA (16S rRNA) gene, fungal internal transcribed spacer-1 (ITS1) gene and algal ribulose-bisphosphate carboxylase (rbcL) gene in soils were subjected to high-throughput sequencing. The occurrence of frames with living snails and density of living snails were compared in marshland with different types of land use. The associations of soil microorganisms and physicochemical properties with the density of living snails were examined using Pearson correlation analysis, and the contributions of soil microorganisms and physicochemical properties to the density of living snails were evaluated using variance partitioning analysis. RESULTS: In marshlands with four types of land use, the greatest occurrence of frames with living snails [(4.94 ± 2.14)%] and density of living snails [(0.070 ± 0.026) snails/0.1 m2] were seen in ditches, and the lowest were found in [(1.23 ± 1.23)%] agricultural cultivation lands [(0.016 ± 0.019) snails/0.1 m2]. A total of 2 phyla, 5 classes, 8 orders, 9 families and 11 genera of algae were detected in soils at four types of land use, with Chlorophyta as the dominant phylum and Pseudoneochloris as the dominant genus. A total of 44 phyla, 134 classes, 281 orders, 338 families and 516 genera of bacteria were detected in soils at four types of land use, with Proteobacteria and Acidobacteriota as the dominant phyla and uncultured Acidobacterium, MND1, Mitrospira, Haliangium and Sphingomonas as dominant genera. A total of 11 phyla, 41 classes, 108 orders, 223 families and 408 genera of fungi were detected in soils at four types of land use, with phyla Ascomycota, Basidiomycota and Mortierellomycota presenting high relative abundances and genera Cladorrhinum, Mortierella and Humicola presenting high relative abundances. Pearson correlation analysis revealed that the density of living snails correlated negatively with the relative abundance of Proteobacteria (r = -0.965, P < 0.05) and soil electronic conductivity (r = -0.962, P < 0.05) and positively with soil moisture (r = 0.951, P < 0.05). Variance partitioning analysis demonstrated that the physicochemical properties and microorganisms of soil contributed 69% and 10% to the density of living snails, respectively. CONCLUSIONS: The diversity of microbial communities varies in soils at different types of land use in marshland along the Yangtze River basin, and the physicochemical properties and microorganisms of soils may affect the distribution of O. hupensis snails.

[Epidemiological characteristics and spatial aggregation of acute myocardial infarction in Shandong Province].

Objective: To understand the characteristics and trends of acute myocardial infarction (AMI) in Shandong Province and to provide evidence for formulating prevention and control strategies. Methods: Data were derived from the AMI incidence reports of Shandong Province's Chronic Disease Surveillance Information Management System in 2012-2021. The crude and standardized incidence rates were used as indicators to describe the incidence level of AMI. Joinpoint regression analysis was used to analyze the trends in the incidence and age of onset over the years. The contribution of population aging to the increase in AMI incidence was assessed using the rate difference decomposition method. The incidence of AMI in each district (county) in Shandong Province was visualized using ArcGIS 10.8 software, and global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software. Results: From 2012 to 2021, 198 233 cases of AMI were reported from 19 provincial monitoring sites in Shandong Province, of which 53.13% were males and 97.12% were ≥45 years old. The reported crude incidence increased from 90.12 per 100 000 in 2012 to 176.54 per 100 000 in 2021, with an average annual increase of 7.01% (Z=7.35, P<0.001). There was no significant upward trend in standardized incidence (Z=1.64, P=0.140), but the standardized incidence of male residents showed an increasing trend (Z=2.76, P=0.028). Before 2014, the reported crude incidence of males was similar to that of females, but after 2014, the reported crude incidence of males was continuously higher than that of females. However, males' standardized incidence was higher than females in all years. Both crude and standardized incidence rates were higher in rural residents than in urban areas. The median onset of AMI increased from 71.6 years old in 2012 to 73.5 years old in 2021. The median age of onset in males was lower than that in females in all years, and in most years, the median age of onset in urban residents was lower than that in rural residents. The incidence of AMI in males showed a trend in younger age groups. According to the seasonal decomposition, the incidence peak of AMI was in January, and the trough was in September. The contribution of aging population to the increase in crude incidence of AMI increased from 8.63% in 2013 to 52.58% in 2021. The global spatial autocorrelation analysis showed that the incidence of AMI presented an obvious spatial clustering distribution. Local spatial autocorrelation analysis found that the high-incidence areas (counties) were mainly concentrated in Liaocheng City and Dezhou City in the northwest region of Shandong Province and Heze City in the southwest. Conclusions: The incidence of AMI among residents in Shandong Province was rising, with spatial clustering and seasonal clustering characteristics. People aged 45 years and older, male residents, and rural residents were at high risk of developing AMI. There was a certain trend of younger age at onset among men. Targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustering areas in northwestern Shandong Province.

[Epidemiological characteristics of spontaneous subarachnoid hemorrhage cases in Shandong province].

Objective: To investigate the characteristics and trends of spontaneous subarachnoid hemorrhage (SAH) in Shandong province. Methods: In this study, SAH incidence data of residents from 2012 to 2021 were collected from the chronic disease monitoring information management system of Shandong province, including the basic information of outpatient, emergency or inpatient cases and out-of-hospital deaths (name, gender, ID number, address, etc.) and disease diagnosis information (disease diagnosis, date of onset, date of diagnosis, etc.). The crude incidence rate and age-standardized incidence rate were used as indicators to describe the incidence of SAH in different gender, age groups and regions (urban and rural areas). Joinpoint regression was used to analyze the variation of incidence rate and age by year. The rate difference decomposition method was used to estimate the contribution of population aging to the increase of SAH incidence. Global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software. Results: From 2012 to 2021, a total of 11 629 cases of SAH were reported from 19 provincial monitoring sites in Shandong province. Among them, 54.11% (6 293 cases) were female and 91.87% (10 684 cases) were≥45 years old. The reported crude incidence rate increased from 5.26/100 000 to 9.50/100 000, with an average annual increase of 7.75% (Ztrend=7.30, Ptrend<0.001), and the standardized incidence rate also showed an upward trend (Ztrend=3.92, Ptrend=0.004). The crude incidence rate of women was higher than that of men in all years (all P values<0.05), and the standardized incidence rate of women was higher than that of men in all years except in 2012 and 2021 (all P values<0.05). In 2012, the crude incidence and standardized incidence of urban residents were lower than those in rural areas (P<0.05); from 2013 to 2017, the urban incidence was higher than that in rural areas; and after 2018, the rural incidence exceeded the urban incidence again (all P values<0.05). The median age of onset of SAH increased from 61.9 years in 2012 to 67.2 years in 2021. The age of onset of SAH in men was lower than that in women in all years (all P<0.05), and there was no significant difference between urban and rural residents in most years (P>0.05). The incidence of SAH increased with age (Ptrend<0.001), with a low incidence reported in residents aged<45 years and a rapid increase in residents aged≥45 years. According to the seasonal decomposition, the incidence of SAH had three small peaks in January, March to May and October to November. From 2013 to 2021, the contribution of aging population to the increase of crude incidence of SAH increased from 27.86% to 43.68%. The global spatial autocorrelation analysis showed that the incidence of SAH was in an obvious spatial aggregation distribution (Moran's I>0, P<0.05). Local spatial autocorrelation analysis showed that the counties with high incidence were mainly concentrated in Dezhou City in northwest Shandong Province and Heze city in southwest Shandong province. Conclusions: The crude incidence rate of SAH in Shandong province is increasing, with spatial clustering and seasonal clustering. Residents aged 45 years and older, female residents, and rural residents are at high risk of developing SAH, so targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustered areas.

[Retrospective study of role of neoadjuvant rectal scores in evaluating the 10-year disease-free survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy followed by surgery].

Objective: To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy. Methods: Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores. Results: Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46-63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44-58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1-2 in 246 patients (50.5%) and 3-4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8-16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7-133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8-16, and >16 were 85.1%, 80.5%, and 66.4%, respectively (P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408-0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559-4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer (P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62-0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49-0.60). The two scores differed significantly in accuracy (Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion: The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.

[Research progress on the association between sarcopenia and cardiometabolic diseases among older adults].

Sarcopenia and cardiometabolic diseases have become important public health problems affecting the health and quality of life of the elderly. Reducing the incidence of sarcopenia is of positive significance for preventing and treating cardiometabolic diseases. This paper reviews the diagnostic criteria of sarcopenia in the elderly, the relationship between sarcopenia and cardiometabolic diseases, and the possible mechanisms. It provides support for the prevention and control of sarcopenia combined with cardiometabolic diseases.

Diabetes and long duration leading to speech-, low/mid-, and high- frequency hearing loss: current evidence from the China National Health Survey 2023.

PURPOSE: To examine the effect of diabetes, duration of diabetes, and blood glucose on speech-, low/mid-, and high-frequency hearing loss. METHODS: In this cross-sectional study, 2821 participants aged 20-87 years in the China National Health Survey were included. Diabetes was defined as valid fasting blood glucose (FBG) of ≥ 7.0 mmol/L, a self-reported history of diabetes or the use of anti-diabetic medications. Speech-(500, 1000, 2000, and 4000 Hz), low/mid- (500, 1000 and 2000 Hz), and high-frequency (4000, 6000, and 8000 Hz) hearing loss was defined as pure tone average of responding frequencies > 20 dB HL in the better ear, respectively. RESULTS: In fully adjusted models, for speech-, low/mid-, and high-frequency hearing loss, compared with no diabetes, those with diabetes (OR[95%CI]: 1.44 [1.12, 1.86], 1.23 [0.94, 1.61], and 1.75 [1.28, 2.41], respectively) and with diabetes for > 5 years duration (OR[95%CI]: 1.63 [1.09, 2.42], and 1.63 [1.12, 2.36], 2.15 [1.25, 3.70], respectively) were at higher risk. High FBG level was associated with a higher risk of speech-, low/ mid-, and high-frequency hearing loss. And there were stronger associations between HL and diabetes, longer duration and higher in "healthier population" (no hypertension, no dyslipidemia and younger age). CONCLUSION: Diabetes, longer duration, and higher FBG level were independently associated with hearing loss for speech-, low/mid- and high-frequency hearing loss, particularly in higher frequency and "healthier population". Paying more attention to hearing loss in those populations could lower the burden of hearing loss.

What impact does hearing impairment have on cognitive health in older married couples in China?

Hearing impairment is a common geriatric health problem and chronic stressor, and it is associated with poor cognitive outcomes. However, little is known about the impact of hearing impairment in married couples, particularly its potential spillover effects on the cognitive health among spouses of individuals with impairment. Drawing on a stress-proliferation perspective, we used actor-partner interdependence models to examine (1) whether an individual's hearing impairment influences their spouse's cognitive function; and (2) whether AL, symptoms of depression, and social participation serve as mediators for such an association. We utilized data from the 2015 (baseline) and 2018 (3-year follow-up) waves of the China Health and Retirement Longitudinal Study. 4434 couples were included at baseline, and 2190 couples remained after the 3-year follow-up. Hearing impairment among married women was associated with negative impacts on their spouses' cognitive function. Symptoms of depression and social participation may have served as potential mediators in this relationship. For married men, there was no statistically significant association between hearing impairment and spouses' cognitive function. Our findings suggest that hearing impairment among one spouse can lead to negative impacts on the other, but that this effect may depend on gender. Early diagnosis and couple-based interventions for hearing impairment are important for the cognitive health of both hearing-impaired individuals and their spouses.

[A successfully treated case of respiratory failure caused by eating Nassariidaes].

Food poisoning caused by Nassariidaes has occurred frequently in coastal areas of China, especially in summer and autumn. Nassariidaes poisoning can be manifested as lip and tongue paralysis, dizziness, headache, nausea and vomiting, arrhythmia and even respiratory failure. We admitted a case of respiratory failure caused by eating Nassariidaes. After timely respiratory support, hemoperfusion and other active treatment, the patient was recovered and was discharged. This paper summarized clinical characteristics and treatment of Nassariidaes poisoning, in order to provide reference for clinical diagnosis and treatment of similar cases.

[Single extract of Forsythia Suspense versus the prepared drug in pieces: comparison of their anti-inflammatory, antitumor and antibacterial effects in zebrafish].

OBJECTIVE: To compare the anti-inflammatory, antitumor and anti-bacterial effects of the single extract (in granules) and the prepared drug in pieces of Forsythia Suspense (Lianqiao, a traditional Chinese herbal medicine). METHODS: In zebrafish embryo models of CuSO4 exposure, tail transection and LPS microinjection-induced inflammation, the anti-inflammatory effects of 10 µg/mL DEX, single extract of Forsythia Suspense, and the water extract of the prepared drug (400, 600, and 800 µg/mL) were evaluated by observing neutrophil counts, RT- qPCR, HE staining and survival analysis. Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining. The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs. RESULTS: In the zebrafish embryo models of inflammation, both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation, reduced the mRNA expressions of TNF-α, IL-6, P38, Jnk, Erk and P65, and increased the survival rate of zebrafish. They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells (HCT116), pancreas adenocarcinoma cells (PANC-1), lung cancer cells (A549), liver cancer cells (Hep3B) and cervical carcinoma cells (Hela) in zebrafish embryos, and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL. CONCLUSION: The two dosage forms of Forsythia Suspense have similar anti-inflammatory, antitumor and antibacterial effects, but their effects for inhibiting IL-6, P65, and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish.

[Screening of differentially expressed genes in gastric cancer based on GEO database and function and pathway enrichment analysis].

OBJECTIVE: To explore the core genes related to the diagnosis and prognosis of gastric cancer (GC) based on Gene Expression Omnibus (GEO) database and screen the molecular targets involved in the occurrence and development of GC. METHODS: GC microarray data GSE118916, GSE54129 and GSE79973 were downloaded from GEO database, and the differentially expressed genes (DEGs) were screened. Enrichment analysis of the signaling pathways and molecular functions were preformed and protein-protein interaction networks (PPI) were constructed to identify the hub genes, whose expression levels and diagnostic and prognostic values were verifies based on gastric adenocarcinoma data from TCGA. The expression levels of these core genes were also detected in different GC cell lines using qRT- PCR. RESULTS: Seventy-seven DEGs were identified, which encodes proteins located mainly in the extracellular matrix and basement membrane with activities of oxidoreductase and extracellular matrix receptor and ligand, involving the biological processes of digestion and hormone metabolism and the signaling pathways in retinol metabolism and gastric acid secretion. Nine hub genes were obtained, among which SPARC, TIMP1, THBS2, COL6A3 and THY1 were significantly up- regulated and TFF1, GKN1, TFF2 and PGC were significantly down-regulated in GC. The abnormal expressions of SPARC, TIMP1, THBS2, COL6A3, TFF2 and THY1 were significantly correlated with the survival time of GC patients. ROC curve analysis showed that aberrant expression of TIMP1 SPARC, THY1 and THBS2 had high diagnostic value for GC. High expressions of SPARC, TIMP1, THBS2 and COL6A3 were detected in GC tissues. In the GC cell lines, qRT- PCR revealed different expression patterns of these hub genes, but their expressions were largely consistent with those found in bioinformatics analyses. CONCLUSION: SPARC, TIMP1, THBS2 and other DEGs are probably involved in GC occurrence and progression and may serve as potential candidate molecular markers for early diagnosis and prognostic evaluation of GC.

Discovery of New Isotopes

Using the fusion-evaporation reaction ^{106}Cd(^{58}Ni,4n)^{160}Os and the gas-filled recoil separator SHANS, two new isotopes _{76}^{160}Os and _{74}^{156}W have been identified. The α decay of ^{160}Os, measured with an α-particle energy of 7080(26) keV and a half-life of 201_{-37}^{+58} µs, is assigned to originate from the ground state. The daughter nucleus ^{156}W is a ß^{+} emitter with a half-life of 291_{-61}^{+86} ms. The newly measured α-decay data allow us to derive α-decay reduced widths (δ^{2}) for the N=84 isotones up to osmium (Z=76), which are found to decrease with increasing atomic number above Z=68. The reduction of δ^{2} is interpreted as evidence for the strengthening of the N=82 shell closure toward the proton drip line, supported by the increase of the neutron-shell gaps predicted in theoretical models.

[Genotype-phenotype analysis of Fabry disease caused by GLA gene variation in a pedigree].

Objective: To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A. Methods: It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 µmol/(L·h) or elavated Lyso-GL-3 level>1.10 µg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed. Results: The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband's father had knee joint pain. The proband's elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband's fifth aunt with a GLA variant had decreased vision. Conclusions: High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

Prognostic significance of serum cystatin C in acute brainstem infarctions patients.

OBJECTIVES: Some studies show that high circulating cystatin C (CysC) may predict cardiovascular events and death after ischemic stroke onset. However, the association between serum CysC and outcome in ischemic stroke patients remains contradictory. We sought to assess the association between a specific stroke subgroup, brainstem infarction (BSI) and serum CysC. MATERIALS AND METHODS: A total of 324 acute BSI patients were included in the study. Serum CysC was used to calculate estimated glomerular filtration rate (eGFRCysC) at baseline. Modified Rankin scale score ((mRS) ≥3) six months after acute BSI indicates poor functional outcome. Patients were categorized into two groups according to mRS and eGFRCysC. Logistic regression analyses were performed to determine independent risk factors. RESULTS: Lower eGFRCysC was associated with hemoglobin A1c (HbA1c). This risk remained statistically significant after controlling for age, hypertension, initial National Institutes of Health Stroke Scale (NIHSS) score, HbA1c, fibrinogen and homocysteine. The serum eGFRCysC levels were significantly lower in the poor functional outcome group than the good functional outcome group (P<0.001). Multivariate logistic regression analyses showed that eGFRCysC level was significantly lower in the poor outcome group after adjusting for age, previous infarctions, initial NIHSS score, and HbA1c. CONCLUSIONS: Lower eGFRCysC levels were strongly associated with poor functional outcome of acute BSI patients with a higher HbA1c level. Lower eGFRCysC may be a more helpful serologic biomarker for the prediction of prognosis in BSI.

[Short-term outcomes of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer].

Objective: To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC). Methods: This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9(M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)µg/L(range: 1.4 to 13.4 µg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient's death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results: After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the "standardised pathology protocol" and the "1 mm" principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion: Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.

Three-dimensional pseudo-continuous arterial spin-labelled perfusion imaging for diagnosing upper cervical lymph node metastasis in patients with nasopharyngeal carcinoma: a whole-node histogram analysis.

AIM: To evaluate whole-node histogram parameters of blood flow (BF) maps derived from three-dimensional pseudo-continuous arterial spin-labelled (3D pCASL) imaging in discriminating metastatic from benign upper cervical lymph nodes (UCLNs) for nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: Eighty NPC patients with a total of 170 histologically confirmed UCLNs (67 benign and 103 metastatic) were included retrospectively. Pre-treatment 3D pCASL imaging was performed and whole-node histogram analysis was then applied. Histogram parameters and morphological features, such as minimum axis diameter (MinAD), maximum axis diameter (MaxAD), and location of UCLNs, were assessed and compared between benign and metastatic lesions. Predictors were identified and further applied to establish a combined model by multivariate logistic regression in predicting the probability of metastatic UCLNs. Receiver operating characteristic (ROC) curves were used to analyse the diagnostic performance. RESULTS: Metastatic UCLNs had larger MinAD and MinAD/MaxAD ratio, greater energy and entropy values, and higher incidence of level II (upper jugular group), but lower BF10th value than benign nodes (all p<0.05). MinAD, BF10th, energy, and entropy were validated as independent predictors in diagnosing metastatic UCLNs. The combined model yielded an area under the curve (AUC) of 0.932, accuracy of 84.42 %, sensitivity of 80.6 %, and specificity of 90.29 %. CONCLUSIONS: Whole-node histogram analysis on BF maps is a feasible tool to differentiate metastatic from benign UCLNs in NPC patients, and the combined model can further improve the diagnostic efficacy.

[Evaluation of brain age changes in patients with liver cirrhosis and hepatic encephalopathy with deep learning models based on structural magnetic resonance imaging].

Objective: To investigate the brain aging in patients with cirrhosis and hepatic encephalopathy(HE), constructed a prediction model of brain age based on deep learning and T1 high-resolution MRI, and try to reveal the specific regions where cirrhosis and HE accelerating brain aging. Methods: A cross-sectional study. A brain age prediction model based on the 3D full convolutional neural network was constructed through T1 high-resolution MRI data from 3 609 healthy individuals across eight global public datasets. The mean absolute error (MAE) between actual age and predicted brain age, Pearson correlation coefficient (r) and determination coefficient (R2) were calculated to evaluate the accuracy of the model's predictions. A test set (n=555) from the Human Connectome Project was used to assess the accuracy of the model. A total of 136 patients with cirrhosis were recruited from Tianjin First Central Hospital as the case group (79 patients with cirrhosis without HE and 57 patients with cirrhosis with HE), and 70 healthy individuals were recruited from the society as the healthy control group during the same period. Brain-predicted age difference (Brain-PAD), digital connection-A (NCT-A) and digital-symbol test (DST) scores of all subjects were calculated for all subjects to assess brain aging and cognitive function in the healthy control group, the cirrhosis without HE group, and the cirrhosis with HE group. The network occlusion sensitivity analysis method was employed to assess the importance of each brain region in predicting brain age. Results: As for the prediction model, in the training set, MAE=2.85, r=0.98, R2=0.96. In the test set, MAE=4.45, r=0.96, R2=0.92. In the local data set of the healthy control group, MAE=3.77, r=0.85, R2=0.73. The time of NCT-A in both cirrhosis groups was longer than healthy control group, while the DST scores were lower than healthy control group, and the differences were statistically significant (both P<0.001); the Brain-PAD of healthy control group was (0.8±4.5) years, the Brain-PAD of no-HE group was (6.9±8.1) years, and the HE group was (10.2±7.7) years. The differences between the three groups were statistically significant (P<0.001), and the differences between any two groups were statistically significant (all P<0.05). The importance ratio of visual network in predicting brain age increased in cirrhosis patients, and the HE group was higher than no-HE group. Conclusions: In patients with cirrhosis, the cognitive function is reduced, brain aging is accelerated, and these changes are more obvious in patients with HE. The importance differences of each brain network in predicting brain aging provide a new direction for identifying the specific regions where cirrhosis and HE accelerate brain aging.

[Analysis of the incidence and mortality of thyroid cancer in Shandong Province from 2012 to 2022 based on the age-period-cohort model].

Objective: To analyze the trend of incidence and mortality of thyroid cancer and estimate its age-period-cohort effect in Shandong Province from 2012 to 2022. Methods: The Joinpoint regression was used to analyze the trend of incidence and mortality of thyroid cancer and calculate the average annual percentage change (AAPC) based on the data on thyroid cancer from 2012 to 2022. The age-period-cohort model was used to analyze the age-effect, time-effect and cohort-effect of thyroid cancer risk in the population aged over 20 years. Results: From 2012 to 2022, the incidence of thyroid cancer in Shandong province showed a significant upward trend, with an AAPC of 21.68% (95%CI: 19.14%-24.27%, P<0.001). The incidence of females was higher than that of males, and the incidence of urban areas was higher than that of rural areas. The trend of thyroid cancer mortality was relatively stable with an AAPC of -3.04% (95%CI:-8.81%-3.09%, P=0.323). The age effect of incidence increased with age before 60 years old and decreased with age after 60 years old. The incidence peaked in the age group of 55-59. The period effect increased with time. The cohort effect showed that the cohort born before 1957 had a downward trend over time, while the cohort born after 1957 had an upward trend. Conclusion: The incidence of thyroid cancer in Shandong shows a rising trend from 2012 to 2022. Age is an important factor affecting the risk of thyroid cancer. The mortality of thyroid cancer remains stable.

[MACC1 knockdown enhances RSL3-induced ferroptosis in human colorectal cancer cells by inhibiting GPX4 expression].

OBJECTIVE: To investigate the effect of MACC1 on RSL3-induced ferroptosis in colorectal cancer cells and explore its molecular mechanism. METHODS: MACC1 expression was detected in SW620, HCT116, LOVO and RKO cells using Western blotting. The effects of different concentrations of RSL3 (an inducer of ferroptosis) or Fer-1 (an inhibitor of ferroptosis) alone, or 10 µmol/L RLS3 combined with 10 µmol/L Fer-1, on viability of SW620 cells were examined using MTT assay. The survival of SW620 cells with mRNA interference of MACC1 was analyzed following treatment with RSL3, and RT-qPCR and Western blotting were performed to detect the changes in MACC1 expressions after RSL3 treatment at different concentrations and the changes in GPX4 expression after MACC1 knockdown. Flow cytometry and laser confocal microscopy were used to analyze the changes in ROS-induced lipid peroxidation in SW620 cells after MACC1 knockdown. RESULTS: SW620 cells had the highest MACC1 expression among the 4 colorectal cancer cell lines. Treatment with RSL3 significantly inhibited the viability of SW620 cells in a dose-dependent manner, while Fer-1 did not significantly affect the survival of SW620 cells. RSL3 alone reduced SW620 cell survival by 50% (P < 0.01), and the combined treatment with RSL3 and Fer-1 caused no significant changes in cell survival (P > 0.05). Treatment with RSL3 concentration-dependently suppressed MACC1 expressions at both the mRNA and protein levels in SW620 cells (P < 0.01). MACC1 knockdown obviously enhanced the cytotoxic effect of RSL3, inhibited the expression of GPX4, and increased ROS-induced lipid peroxidation in SW620 cells (P < 0.05). CONCLUSION: MACC1 knockdown enhances RSL3-induced ferroptosis in cultured colorectal cancer cells by inhibiting the expression of GPX4.