[A rapidly enlarging neck mass]. / Een snelgroeiende zwelling in de hals.

The differential diagnosis of a rapidly enlarging neck mass consists of many different benign ((haemorrhagic) cyst) and malignant (anaplastic thyroid cancer (ATC) and lymphoma) causes. ATC is a rare disease with a median survival of 6 months. As early diagnosis and management are key for fast-growing cancers, in our centre we have implemented a dedicated short-stay in-hospital fast-track diagnostic work-up for patients with a rapid growing mass in the neck. The goal of this track is to have a fast diagnostic and therapeutic plan for this disease. Based on three clinical cases we discuss our experience with this fast-track diagnostic work-up for rapidly growing mass in the neck and illustrate the additional value in this clinical entity.

[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.

[Identification of key genes in Wilms tumor based on high-throughput RNA sequencing and their impacts on prognosis and immune responses].

OBJECTIVE: To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. METHODS: High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. RESULTS: Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5- and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. CONCLUSION: TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.

ENAM Mutations Can Cause Hypomaturation Amelogenesis Imperfecta.

Amelogenesis imperfecta (AI) is a diverse group of inherited diseases featured by various presentations of enamel malformations that are caused by disturbances at different stages of enamel formation. While hypoplastic AI suggests a thickness defect of enamel resulting from aberrations during the secretory stage of amelogenesis, hypomaturation AI indicates a deficiency of enamel mineralization and hardness established at the maturation stage. Mutations in ENAM, which encodes the largest enamel matrix protein, enamelin, have been demonstrated to cause generalized or local hypoplastic AI. Here, we characterized 2 AI families with disparate hypoplastic and hypomaturation enamel defects and identified 2 distinct indel mutations at the same location of ENAM, c588+1del and c.588+1dup. Minigene splicing assays demonstrated that they caused frameshifts and truncation of ENAM proteins, p.Asn197Ilefs*81 and p.Asn197Glufs*25, respectively. In situ hybridization of Enam on mouse mandibular incisors confirmed its restricted expression in secretory stage ameloblasts and suggested an indirect pathogenic mechanism underlying hypomaturation AI. In silico analyses indicated that these 2 truncated ENAMs might form amyloid structures and cause protein aggregation with themselves and with wild-type protein through the added aberrant region at their C-termini. Consistently, protein secretion assays demonstrated that the truncated proteins cannot be properly secreted and impede secretion of wild-type ENAM. Moreover, compared to the wild-type, overexpression of the mutant proteins significantly increased endoplasmic reticulum stress and upregulated the expression of unfolded protein response (UPR)-related genes and TNFRSF10B, a UPR-controlled proapoptotic gene. Caspase, terminal deoxynucleotidyl transferase UTP nick-end labeling (TUNEL), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays further revealed that both truncated proteins, especially p.Asn197Ilefs*81, induced cell apoptosis and decreased cell survival, suggesting that the 2 ENAM mutations cause AI through ameloblast cell pathology and death rather than through a simple loss of function. This study demonstrates that an ENAM mutation can lead to generalized hypomaturation enamel defects and suggests proteinopathy as a potential pathogenesis for ENAM-associated AI.

Mortality associated with polymyalgia rheumatica in the United States in the 1999-2020 period: a multiple-cause-of-death study.

OBJECTIVE: Multicause-of-death methods were used to analyze mortality and leading causes of death associated with polymyalgia rheumatica (PMR) in the United States from 1999 to 2020. MATERIALS AND METHODS: We analyzed mortality data from the Centers for Disease Control and Prevention (CDC) Data analysis system and selected death certificates that listed PMR as the cause of death based on the International Statistical Classification of Diseases and Related Health Problems (ICD-10) category code. Relevant mortality rates, number of deaths and historical trends were analyzed. The number of PMR-related deaths and age-standardized mortality rate (ASMR) trend charts were made using Excel 2010 version and trend lines were added. RESULTS: Over the last 22 years, the total number of PMR-related deaths in the United States was 15,421 women (89.8%), a ratio of about 1:9 men to women. When PMR is listed as the underlying cause of death, the ASMR for women and men (per 100,000 people) is approximately 1.8-5.1:1, and when it is listed as the non-underlying cause of death, it is 1.8-3.3:1. PMR deaths are more frequent in individuals aged 70 years and above, with patients aged 80 years and above being most affected. Among different ethnicities, the highest number of deaths was found in Caucasians, followed by Black or African American. When it comes to causes of death, heart disease still ranks first, followed by cancer. In addition, we also found that when PMR combined with malignant tumors as a multiple cause of death, the number of female deaths was higher than that of male deaths, the overall number of deaths of both showed an upward trend, and the overall ASMR of both showed a downward trend. CONCLUSIONS: In the past 22 years, we have observed a low mortality rate of PMR in the United States. However, for patients with PMR, especially elderly women, medical workers should be vigilant and pay attention to whether they are combined with other complications, such as malignant neoplasms, and make timely diagnosis and treatment to further reduce the mortality rate of patients with PMR.

Clinical study of tirofiban compared to low molecular weight heparin in the antithrombotic treatment of progressive pontine infarction.

OBJECTIVE: To investigate the efficacy and safety of tirofiban and low molecular weight heparin (LMWH) in the treatment of patients undergoing acute progressive pontine infarction. PATIENTS AND METHODS: Patients with acute progressive pontine infarction who were hospitalized in the Neurology Department from June 2021 to June 2023 were included in the study and randomly divided into two groups, namely the experimental group (tirofiban group) and the control group (LMWH group). All patients in both groups were required to receive conventional comprehensive treatment and dual antiplatelet therapy with aspirin + clopidogrel at the beginning of admission. The National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) were used to evaluate the neurological deficits on the first day of admission, the next day with stroke progression, and at discharge after treatment with tirofiban and LMWH, respectively in the two groups. The modified Rankin Scale was employed to assess prognosis on the 90th day after treatment. Clinical adverse events were followed up for 90 days, comparing the clinical efficacy and safety of the two treatment methods. RESULTS: There was no statistical significance in NIHSS score and Barthel Index between the tirofiban group and the LMWH group on the first day of admission and the next day with stroke progression (p > 0.05). After stroke progression, tirofiban and LMWH were separately used for treatment in the two groups. We found that the NIHSS score of the tirofiban group was lower than that of the LMWH group, and the Barthel Index score was higher than that of the LMWH group at discharge (p < 0.05). After three months of follow-up, the mRS score of the tirofiban group was dramatically higher than that of the LMWH group (p < 0.05). No significant harmful or adverse reactions, such as bleeding events, were found in the two groups (p > 0.05). CONCLUSIONS: Tirofiban may be more effective and safer than LMWH in controlling the progression of acute pontine infarction, but further and large-sample studies are still needed to confirm this finding.

Effect of intravenous and topical laryngeal lidocaine on sore throat after extubation: a prospective randomized controlled study.

OBJECTIVE: The present study aimed to compare the effect of topical laryngeal lidocaine with intravenous lidocaine before endotracheal intubation on the incidence and severity of postoperative sore throat, hoarseness, and cough. PATIENTS AND METHODS: This prospective randomized controlled study enrolled 144 patients undergoing laparoscopic cholecystectomy with endotracheal intubation. The patients were randomized to three groups and received 2% lidocaine by topical laryngeal spray (group T), intravenous 2% lidocaine (group I), and the equivalent volume of intravenous saline (group C) before intubation. The incidence and severity of sore throat, hoarseness, and cough reaction at 0.5, 1, 6, and 24 h after extubation were collected. RESULTS: The incidence of sore throat was significantly lower in group T than in groups I and C (6.4% vs. 37.2% and 86.7%, p < 0.001), respectively at 0.5 h after extubation, and it was significantly lower in group I than that in group C (37.2% vs. 86.7%, p < 0.001). Both the incidence of hoarseness and cough were significantly lower in group T than in group I and in group C (14.9% vs. 97.7% and 97.8%, p < 0.001, and 19.1% vs. 72.0% and 93.3%, p < 0.001), respectively. The severity of sore throat, hoarseness and cough in group T was significantly lower than that in group I and that in group C (p < 0.05), and it was significantly lower in group I than in group C (p < 0.05). CONCLUSIONS: Both topical laryngeal lidocaine and intravenous lidocaine before intubation have positive effects on preventing sore throat. Topical laryngeal route was superior to intravenous route. Chictr.org.cn ID: ChiCTR2100042442.

Drought priming-induced stress memory improves subsequent drought or heat tolerance via activation of γ-aminobutyric acid-regulated pathways in creeping bentgrass.

Recurrent drought can induce stress memory in plants to induce tolerance to subsequent stress, such as high temperature or drought. Drought priming (DP) is an effective approach to improve tolerance to various stresses; however, the potential mechanism of DP-induced stress memory has not been fully resoved. We examined DP-regulated subsequent drought tolerance or thermotolerance associated with changes in physiological responses, GABA and NO metabolism, heat shock factor (HSF) and dehydrin (DHN) pathways in perennial creeping bentgrass. Plants can recover after two cycle of DP, and DP-treated plants had significantly higher tolerance to subsequent drought or heat stress, with higher leaf RWC, Chl content, photochemical efficiency, and cell membrane stability. DP significantly alleviated oxidative damage through enhancing total antioxidant capacity in response to subsequent drought or heat stress. Endogenous GABA was significantly increased by DP through activating glutamic acid decarboxylase activity and inhibiting GABA transaminase activity. DP also enhanced accumulation of NO, depending on NOS activity, under subsequent drought or heat stress. Transcript levels of multiple transcription factors, heat shock proteins, and DHNs in the HSF and DHN pathways were up-regulated by DP under drought or heat stress, but there were differences between DP-regulated heat tolerance and drought tolerance in these pathways. The findings indicate that under recurrent moderate drought, DP improves subsequent tolerance to drought or heat stress in relation to GABA-regulated pathways, providing new insight into understanding of the role of stress memory in plant adaptation to complex environmental stresses.

Prospects of targeting JAK/STAT signal transduction pathways for vasculitis.

Vasculitis is the inflammation of blood vessels caused by autoimmunity and/or autoinflammation, and its etiology and pathogenesis remain largely unknown. The Janus kinase (JAK) and Signal transduction Transcription Activator (STAT) signal transduction pathways are a group of molecules involved in the major pathways by which many cytokines exert and integrate their functions, and their dysregulation has been implicated in the pathogenesis of a variety of autoimmune diseases. However, current data supporting the role of the JAK/STAT pathway in the development of vasculitis is limited. In terms of treatment, glucocorticoids and immunosuppressants have been the standard therapy. However, because of the huge burden of treatment side effects, people have long waited for new treatment options. JAK inhibitors reduce the production of multiple cytokines and inhibit inflammation by targeting the JAK/STAT pathway, and have the advantage of rapidly acting in oral formulations, reducing glucocorticoid dependence and associated adverse events, especially in refractory cases. Therefore, JAK inhibitors are expected to be a promising drug for the treatment of vasculitis.

[A multicenter prospective study on early identification of refractory Mycoplasma pneumoniae pneumonia in children].

Objective: To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods: The prospective multicenter study was conducted in Zhejiang, China from May 1st, 2019 to January 31st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results: A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95%CI 0.593-0.771, P<0.01). Conclusion: In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

[Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection].

Objective: To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection. Methods: This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group (n=168) and the non-TO group (n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results: Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score (OR=0.488, 95%CI: 0.278 to 0.856, P=0.012) and ypN stage (OR=0.626, 95%CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS (HR=0.662, 95%CI: 0.457 to 0.959,P=0.029) and DFS (HR=0.687, 95%CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion: TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

Telomere dynamics during hibernation in a tropical primate.

Hibernation is a widespread metabolic strategy among mammals for surviving periods of food scarcity. During hibernation, animals naturally alternate between metabolically depressed torpor bouts and energetically expensive arousals without ill effects. As a result, hibernators are promising models for investigating mechanisms that buffer against cellular stress, including telomere protection and restoration. In non-hibernators, telomeres, the protective structural ends of chromosomes, shorten with age and metabolic stress. In temperate hibernators, however, telomere shortening and elongation can occur in response to changing environmental conditions and associated metabolic state. We investigate telomere dynamics in a tropical hibernating primate, the fat-tailed dwarf lemur (Cheirogaleus medius). In captivity, these lemurs can hibernate when maintained under cold temperatures (11-15 °C) with limited food provisioning. We study telomere dynamics in eight fat-tailed dwarf lemurs at the Duke Lemur Center, USA, from samples collected before, during, and after the hibernation season and assayed via qPCR. Contrary to our predictions, we found that telomeres were maintained or even lengthened during hibernation, but shortened immediately thereafter. During hibernation, telomere lengthening was negatively correlated with time in euthermia. Although preliminary in scope, our findings suggest that there may be a preemptive, compensatory mechanism to maintain telomere integrity in dwarf lemurs during hibernation. Nevertheless, telomere shortening immediately afterward may broadly result in similar outcomes across seasons. Future studies could profitably investigate the mechanisms that offset telomere shortening within and outside of the hibernation season and whether those mechanisms are modulated by energy surplus or crises.

[Pulmonary artery stenting in chronic thromboembolic pulmonary hypertension: a report of 2 cases].

Chronic thromboembolic pulmonary hypertension (CTEPH) is a pulmonary vascular disease characterized by an insidious onset, progressive deterioration, and poor prognosis. It is distinguished by the thrombotic organization within the pulmonary arteries, leading to vascular stenosis or occlusion. This results in a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, ultimately leading to right heart failure. In recent years, balloon pulmonary angioplasty (BPA) has emerged as an effective treatment option for patients ineligible for pulmonary endarterectomy (PEA). However, the use of stents in patients with suboptimal balloon dilation remains controversial. This article describes two cases of chronic thromboembolic pulmonary hypertension (CTEPH) in which balloon angioplasty yielded unsatisfactory results, subsequently leading to stent placement. Following stent implantation, there was improved blood flow, significant reduction in pulmonary arterial pressure, and notable alleviation of patient symptoms. One-year follow-up showed no recurrence of stenosis within the stent, suggesting potential guidance for the use of pulmonary artery stenting as a treatment modality for CTEPH. This report provided new insights into the therapeutic approach for CTEPH.

T2-FLAIR mismatch sign and machine learning-based multiparametric MRI radiomics in predicting IDH mutant 1p/19q non-co-deleted diffuse lower-grade gliomas.

AIM: To investigate the application of the T2-weighted (T2)-fluid-attenuated inversion recovery (FLAIR) mismatch sign and machine learning-based multiparametric magnetic resonance imaging (MRI) radiomics in predicting 1p/19q non-co-deletion of lower-grade gliomas (LGGs). MATERIALS AND METHODS: One hundred and forty-six patients, who had pathologically confirmed isocitrate dehydrogenase (IDH) mutant LGGs were assigned randomly to the training cohort (n=102) and the testing cohort (n=44) at a ratio of 7:3. The T2-FLAIR mismatch sign and conventional MRI features were evaluated. Radiomics features extracted from T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), FLAIR, apparent diffusion coefficient (ADC), and contrast-enhanced T1WI images (CE-T1WI). The models that displayed the best performance of each sequence were selected, and their predicted values as well as the T2-FLAIR mismatch sign data were collected to establish a final stacking model. Receiver operating characteristic curve (ROC) analyses and area under the curve (AUC) values were applied to evaluate and compare the performance of the models. RESULTS: The T2-FLAIR mismatch sign was more common in the IDH mutant 1p/19q non-co-deleted group (p<0.05) and the area under the curve (AUC) value was 0.692 with sensitivity 0.397, specificity 0.987, and accuracy 0.712, respectively. The stacking model showed a favourable performance with an AUC of 0.925 and accuracy of 0.882 in the training cohort and an AUC of 0.886 and accuracy of 0.864 in the testing cohort. CONCLUSION: The stacking model based on multiparametric MRI can serve as a supplementary tool for pathological diagnosis, offering valuable guidance for clinical practice.

[Epidemiological characteristics of typhoid fever in Fujian Province, 2011-2022].

Objective: To analyze the incidence trend and epidemiological characteristics of typhoid fever in Fujian Province from 2011 to 2022, and understand the high-incidence population and hotspot areas, and provide evidences to develop more targeted prevention and control measures. Methods: The surveillance data of typhoid fever during 2011-2022 in Fujian Province were obtained from the National Disease Reporting Information System and analyzed with SAS 9.4. The spatial autocorrelation analysis of typhoid fever incidence at county/district levels was performed with ArcGlS 10.8. Results: A total of 5 126 cases of typhoid fever were reported in Fujian Province from 2011 to 2022, with an average annual incidence rate of 1.10/100 000. The average annual incidence rate was 0.96/100 000 from 2011 to 2015, 1.49/100 000 from 2016 to 2019, and 0.81/100 000 from 2020 to 2022. The disease occurred all the year round, with high epidemic season from May to September. A total of 23.59% (1 209/5 126) of the cases occurred at the age of 0-4, and 9.62% (493/5 126) at the age of 5-9. The male to female ratio of the cases was 0.97∶1 (2 524∶2 602) for the whole population, 1.19∶1 (925∶777) for people under 10 years old, 0.75∶1 (1 060∶1 404) for people between 10 and 54 years old, and 1.28∶1 (539∶421) for people over 55 years old. Cases in Ningde City accounted for 30.65% (1 571/5 126) of the total cases. Most hotspots were occurred in Ningde City. Recurrent and clustered cases were found in family members. Conclusions: Typhoid fever was prevalent at a low level in Fujian Province during 2011-2022, indicating that strengthening the prevention and control measures should target key areas and populations. The incidence of typhoid fever in Fujian Province showed spatial aggregation phenomenon, and most cases gathered in Ningde City. Intensive study for the influencing factors of spatial clustering should be conducted.

[Preliminary study on implementation of modified tubular gastric side-overlap anastomosis in laparoscopic proximal gastrectomy].

Objective: To investigate the feasibility and safety of implementing modified tubular gastric side-overlap anastomosis in laparoscopic proximal gastrectomy. Methods: In this retrospective, descriptive case series, we analyzed clinical data of seven patients who had undergone laparoscopic proximal gastrectomy and gastrointestinal reconstruction with modified tubular gastric side-overlap anastomosis from October 2022 to March 2023 in the Second Affiliated Hospital of Fujian Medical University. The study patients comprised five men and two women aged 57-72 years and of body mass index 18.5-25.7 kg/m2. All seven patients had preoperative gastroscopic and pathological evidence of esophagogastric junction cancer and all were found by preoperative enhanced computed tomography and/or endoscopic ultrasonography to have stage CT1-2N0M0 tumors. The main steps in the reconstruction of a modified tubular gastric side-overlap anastomosis are as follows: (1) mobilizing the lower esophagus and opening the left pleura to expand the space; (2) severing the esophagus with a linear cutter stapler; (3) creating a 3-cm-wide tubular stomach along the greater curvature; (4) creating a 5-cm guide line on the lesser curvature of the anterior wall of the tubular stomach and a small opening below the guide line; (5) rotating the esophageal stump 90° counterclockwise and making a small opening on the right posterior wall of the esophageal stump, along with using a 45-mm linear cutter stapler for esophagogastric side-to-side anastomosis under the guidance of the gastric tube and guide line ; (6) closing the common opening using barbed sutures; (7) embedding the cut edge of the esophageal stump such as to closely oppose it to the esophagus; (8) using barbed sutures to continuously suture the lower esophagus bilaterally to the anterior wall of the tubular stomach; and (9) closing the opened esophageal hiatus and pleura. The main outcome measures were intraoperative (operation time, digestive tract reconstruction time, closing the common opening time, intraoperative blood loss, and number of dissected lymph nodes), postoperative (time to passage of flatus , time to liquid diet, time to ambulation, length of postoperative hospital stay, and postoperative complications), pathological (maximum diameter of the tumor and pathological stage) and findings on follow-up. Results: Laparoscopic proximal gastrectomy with reconstruction of a modified tubular gastric side-overlap anastomosis was successfully completed in all seven patients; no conversion to laparotomy was required and there were no postoperative complications. The operation time, digestive tract reconstruction time, and closing of common opening time were 187-229, 61-79, and 7-9 minutes, respectively. Intraoperative blood loss was 15-23 ml and the number of dissected lymph nodes was 14-46 per case. Time to passage of flatus, time to liquid diet, time to ambulation, and postoperative hospital stay were 1-2, 2-3, 3-4, and 6-7 days, respectively. Postoperative pathological examination showed that the maximum tumor diameters were 1.6-3.3 cm in four patients with stage IA disease and three patients with stage IB. The seven patients were followed up for 6-11 months, during which none required routine use of proton pump inhibitors or gastric mucosal protective agents and there were no deaths or tumor recurrence/metastasis. No patients had anemia or hypoproteinemia 3 and 6 months after surgery. Six months after surgery, NRS2002 and GERDQ scores were 1-2 and 2-3, respectively. Gastroscopy showed narrow anastomoses in 6 patients with Los Angeles grade A and one patient with grade B disease. No evidence of significant bile reflux was found and no anastomotic stenosis or reflux was detected on upper gastrointestinal angiography. Conclusion: It is safe and feasible to implement modified tubular gastric side-overlap anastomosis for digestive tract reconstruction in laparoscopic proximal gastrectomy.

Structural insights into peptidoglycan glycosidase EtgA binding to the inner rod protein EscI of the type III secretion system via a designed EscI-EtgA fusion protein.

Bacteria express lytic enzymes such as glycosidases, which have potentially self-destructive peptidoglycan (PG)-degrading activity and, therefore, require careful regulation in bacteria. The PG glycosidase EtgA is regulated by localization to the assembling type III secretion system (T3SS), generating a hole in the PG layer for the T3SS to reach the outer membrane. The EtgA localization was found to be mediated via EtgA interacting with the T3SS inner rod protein EscI. To gain structural insights into the EtgA recognition of EscI, we determined the 2.01 Å resolution structure of an EscI (51-87)-linker-EtgA fusion protein designed based on AlphaFold2 predictions. The structure revealed EscI residues 72-87 forming an α-helix interacting with the backside of EtgA, distant from the active site. EscI residues 56-71 also were found to interact with EtgA, with these residues stretching across the EtgA surface. The ability of the EscI to interact with EtgA was also probed using an EscI peptide. The EscI peptide comprising residues 66-87, slightly larger than the observed EscI α-helix, was shown to bind to EtgA using microscale thermophoresis and thermal shift differential scanning fluorimetry. The EscI peptide also had a two-fold activity-enhancing effect on EtgA, whereas the EscI-EtgA fusion protein enhanced activity over four-fold compared to EtgA. Our studies suggest that EtgA regulation by EscI could be trifold involving protein localization, protein activation, and protein stabilization components. Analysis of the sequence conservation of the EscI EtgA interface residues suggested a possible conservation of such regulation for related proteins from different bacteria.

[A case of high-pressure injection injury of hand complicated with deep chemical burn caused by industrial cement].

This article reports a patient with extensive high-pressure injection injury of the hand combined with deep chemical burn caused by high-pressure injection of industrial cement materials was diagnosed and treated in the Department of Hand Surgery, Xiaolan Hospital Affiliated to Southern Medical University in 2022. The nerves, tendons and blood vessels of the left hand were involved, and the ulnar skin of the left thumb was extensively necrosis, and a large number of extensive cement foreign bodies remained under the skin. Part of the cement was inserted into the joint capsule of the interphalangeal joint. After emergency surgical treatment, the patient was saved successfully, and the wound healed well without chemical poisoning and other related complications, which created conditions for the second stage of flap repair.