[Clinical characteristics and prognosis of brain metastasis in locally advanced rectal cancer].

Objective: To investigate the clinical characteristics of brain metastases after radical surgery for locally advanced rectal cancer (LARC). Methods: The clinical characteristics of LARC with brain metastases treated in the Department of General Surgery, Peking Union Medical College Hospital from 2013 to 2023 were retrospectively analyzed. The inclusion criteria were rectal adenocarcinoma within 15 cm of the anal verge and having undergone radical surgery, and the exclusion criterion was primary malignant tumor of the brain. The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific overall survival (determined as the interval between occurrence of brain metastasis to death from any causes). The Kaplan-Meier method was used for survival analysis. Results: We identified 4500 patients with LARC, 20 (0.4%) of whom had brain metastases. The mean age of patients with brain metastases was 63.8±9.3 years. They comprised five women and 15 men. The brain was the first site of metastasis in four patients (20%) whereas 18 patients had heterochronous extracranial metastases before brain metastasis. Two patients also had multi-organ metastases. The most common manifestations of brain metastases were dizziness and headache (five patients, 25%), sudden onset of limb weakness (four, 20%), sudden speech impairment (two, 10%), and polyopia (two, 10%). The metastases were diagnosed during follow-up in three patients (15%). Four of the patients were asymptomatic (20%). Treatment approaches included surgical resection (six patients, 30%), chemoradiotherapy (nine, 45%), and palliative (five, 25%). The median follow-up time was 45.5 (4-112) months until October 2023. 1y-OS, 3y-OS, and 5y-OS were 95.0%, 62.9%, and 43.3%, respectively. 1y-DFS, 3y-DFS, and 5y-DFS were 55.0%, 25.0%, and 5.0%, respectively. With brain metastasis as the starting point, the median duration of survival was 16 (10.2-21.8) months. Conclusion: The incidence of brain metastasis is relatively low in patients with LARC, who often have multiple synchronous extracranial metastases. Brain metastases lack specific manifestations and more often occur in male patients. Surgical intervention or combined radiotherapy and chemotherapy may improve disease-specific survival to a certain extent. However, the overall prognosis remains poor.

[Establishment and application of infectious disease monitoring, early warning and disposal system].

Using big data and artificial intelligence to establish a multi-point monitoring, early warning, and disposal system to achieve early warning and intervention of infectious disease outbreaks is an important means of controlling the spread of the epidemic. Taking Xiaoshan district as an example, this study analyzes the monitoring contents, warning methods, and application effectiveness of the infectious disease monitoring, early warning and disposal system. Based on Xiaoshan's health big data resources, the system starts with syndrome, disease diagnosis and etiology. Through advanced technologies such as artificial intelligence and block chain, it realizes early identification of infectious disease outbreaks, data fusion, multi-cross collaboration, and closed-loop management. It has improved the sensitivity of clustered outbreaks monitoring and the effectiveness of epidemic disposal and provided a reference for grassroots disease prevention and control departments to establish an infectious disease monitoring and early warning system.

Consensus gene co-expression analysis across multiple intestinal tissues to identify key genes and pathways associated with abdominal fat deposition in broilers.

1. Abdominal fat deposition (AFD) is regulated by multiple intestinal tissues, and changes in the function of intestinal tissues are associated with AFD. Currently, integration of transcriptomic data across multiple intestinal tissues to explore excessive AFD has rarely been reported in broilers.2. In this study, a consensus gene co-expression network across the duodenum, jejunum, ileum and caecum of high- and low-abdominal fat broiler lines (HL and LL) was constructed using a publicly available transcriptomic data set. Combining the results of functional enrichment analyses and differential gene expression analyses, this investigated the genes and biological pathways across the four intestinal tissues that might influence AFD.3. In one expression module, NDUFA5, NDUFS6, NDUFA4, NDUFS4, ATP5H, ATP5J and ATP5C1 were significantly enriched in the oxidative phosphorylation pathway, with GPX2 and GSR significantly enriched in the glutathione metabolism pathway. These genes were significantly downregulated in the four intestinal tissues of the HL compared to LL chickens, which may be associated with AFD by increasing intestinal permeability.4. Lipid metabolism relevant genes were identified in other modules (ALDH7A1, ACSBG1, THEM4 and DECR1), which may be linked to AFD through regulation of lipid metabolism. Interestingly, in the first module, 12 genes were significantly enriched in the proteasome pathway and significantly downregulated in the four intestinal tissues in HL birds compared to LL birds, indicating a link between the proteasome and AFD.

[Clinical efficacy and its influencing factors of vedolizumab in the treatment of ulcerative colitis].

Objective: To analyze the clinical efficacy and its influencing factors of vedolizumab (VDZ) in the treatment of ulcerative colitis (UC). Methods: The patients with moderately-to-severely active UC, who underwent VDZ treatment at the Second Affiliated Hospital of Wenzhou Medical University from November 2020 to November 2023 were retrospectively included. Based on whether 5-aminosalicylic acid (5-ASA) was used in combination with VDZ treatment, the patients were divided into combination group (received combination therapy of VDZ and 5-ASA) and monotherapy group (received monotherapy of VDZ). The clinical response rate and biological remission rate were analyzed at week 14. The clinical remission rate and mucosal healing rate were analyzed at week 38. The differences in efficacy of VDZ between the two groups were compared at week 14 and week 38, respectively. Multivariate logistic regression model was applied to analyze the influencing factors of clinical remission rate and mucosal healing rate in UC patients. Results: A total of 137 patients were included, including 74 males and 63 females, aged 18-76 (44±14) years old; Seventy-six cases in combination group and 61 cases in monotherapy group. At week 14 of VDZ treatment, the clinical response rate and biological remission rate were 79.6% (109/137) and 80.5% (33/41), respectively. At week 38, the clinical remission rate and mucosal healing rate were 78.8% (108/137) and 47.9% (57/119), respectively. There was no significant difference in clinical response rate and biological remission rate between combination group and monotherapy group at week 14 (both P>0.05). The clinical remission rate [85.5% (65/76) vs 70.5% (43/61), P=0.032] and mucosal healing rate [56.5% (39/69) vs 36.0% (18/50), P=0.027] were higher in combination group than those in monotherapy group at week 38. Multivariate logistic regression analysis showed that the combination therapy of VDZ and 5-ASA (OR=2.48, 95%CI: 1.02-6.03) and the clinical response at week 14 (OR=5.05, 95%CI: 1.98-12.85) were influencing factors of clinical remission rate of UC patients at week 38. Moreover, the baseline serum albumin (Alb) level ≥42.5 g/L was the influencing factor for the mucosal healing rate of UC patients at week 38 (OR=4.60, 95%CI: 2.06-10.24). Conclusions: VDZ is effective in treating UC patients. Both the combination of 5-ASA and the clinical response at week 14 are the influencing factors of the clinical remission rate at week 38. In addition, the baseline serum Alb level ≥42.5 g/L is the influencing factor of the mucosal healing rate at week 38.

[Clinicopathological study of 24 cases of monkeypox virus infection-related rashes].

Objective: To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests. Methods: Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope® hybridization and electron microscopy. Results: All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri's bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope® hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions: The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.

Effect of intraoral photobiomodulation therapy on pain perception associated with local anaesthesia infiltration: a systematic review and meta-analysis of randomized controlled trials.

Local anaesthetic injections, commonly used in dentistry and oral surgery, often cause discomfort. This review aimed to examine the impact of intraoral photobiomodulation therapy (PBMT) on pain associated with local anaesthesia. Up to March 2024, two independent reviewers searched four databases, ultimately screening 17 randomized controlled trials for meta-analysis using Stata 17.0. The results indicate that intraoral PBMT application significantly reduces the perception of pain associated with local anaesthetic injections (standardized mean difference (SMD) -0.89, 95% confidence interval (CI) -1.27 to -0.52; P < 0.001). This analgesic effect remained consistent irrespective of concurrent topical anaesthetics, and PBMT was efficacious in paediatric (SMD -0.53, 95% CI -0.89 to -0.17; P = 0.004) and adult (SMD -1.46, 95% CI -2.32 to -0.61; P = 0.001) populations. Subgroup analysis provided very low to low-quality evidence that using a wavelength between 900 nm and 980 nm (SMD -0.87, 95% CI -1.36 to -0.39; P < 0.001) and an irradiation time of 13-40 s (SMD -0.94, 95% CI -1.35 to -0.53; P < 0.001) are associated with significant pain reduction. The use of PBMT could aid in reducing pain perception for patients during dental injections, encouraging earlier presentation for dental consultations.

[Molecular characteristics and antibiotic resistance of Clostridioides difficile isolated from children in China].

Objective: To understand molecular characteristics and antibiotic resistance of Clostridioides (C.) difficile isolated from children in China, and provide data support the development of disease risk assessment and burden studies. Methods: A total of 155 strains of C. difficile isolated from children aged <12 years in 14 provinces (autonomous regions, municipalities) in China from 2010 to 2023 were used for the analyses on molecular characteristics and antibiotic resistance of C. difficile by PCR and drug susceptibility test. Results: A total of 26 sequence types (STs) and 18 ribotypes (RTs) were identified in the 155 C. difficile isolates, in which ST3 (20.65%), ST54 (16.13%), ST35 (12.90%), and RT012/ICDC007 (14.84%), RT001/ICDC001 (11.61%), RT046/ICDC018 (8.39%) were the most common. One highly virulent strain with RT078 and 27 non-toxin-producing strains were also found; the predominant toxin gene was tcdA+tcdB+cdt-. All the strains were sensitive to metronidazole and vancomycin, and there were 29 multidrug-resistant strains, in which 1 strain was resistant to all the seven antibiotics except for vancomycin and metronidazole. Conclusions: Molecular characteristics and antibiotic resistance of C. difficile in children were similar to those in whole population in China, but there were regional distribution differences. It is necessary to strengthen the routine drug-resistance surveillance for C. difficile infection in children in China.

[Effects of normal mitochondrial transplantation on proliferation, apoptosis and stemness of triple-negative breast cancer cells].

Objectives: To observe the mitochondrial morphology of normal and triple-negative breast cancer cells, extract mitochondria from normal cells, and investigate the effects of mitochondrial transplantation on proliferation, apoptosis, and stemness of triple-negative breast cancer cells. Methods: The morphology of mitochondria was observed by transmission electron microscope. Mitochondria were extracted by mitochondrial extraction kit, mitochondrial protein was identified by western blot, and mitochondrial activity was detected by mitochondrial membrane potential detection kit. MitoTracker Green or MitoTracker Deep Red fluorescent probes were used to label the mitochondria of living cells, and the degree of mitochondria entering LTT cells was observed by confocal laser microscopy at 12, 24, and 96 hours. The effects of mitochondrial transplantation on proliferation, apoptosis, and stemness of breast cancer cells were examined by CCK8, colony formation assay, flow cytometry, and sphere formation assay after 24 hours of mitochondrial transplantation. Results: The mitochondria of normal cells were rod-shaped or elongated, while the mitochondria of triple-negative breast cancer cells were swollen and vacuolated. Western blot results showed that cytochrome c oxidase subunit I (MT-CO1) protein encoded by mitochondria was present in the isolated mitochondria. The content of heat shock protein 60 (HSP60) was higher in mitochondria than that in cytoplasm. The result of the multi-mode microplate reader showed that the content of mitochondrial J-aggregates/monomer was 1.67±0.06, which was significantly higher than 0.35±0.04 of the control group (P＜0.001). Exogenous mitochondria were observed in LTT cells at 12, 24, and 96 hours after mitochondrial transplantation. The results of the CCK8 experiment showed that OD450 of LTT cells was 0.27±0.13 after 48 hours transplantation, which was lower than 0.62±0.36 of the control group (P=0.023). The OD450 of MDA-MB-468 cells was 0.30±0.03, which was lower than 0.65±0.10 of the control group (P=0.004). After 120 hours of mitochondrial transplantation, OD450 in both groups was still significantly lower than that in the control group (P＜0.01). The number of clones formed by mitochondrial transplantation of LTT cells was 21.33±7.31, which was lower than 35.22±13.59 of the control group (P=0.016). Flow cytometry showed that the early apoptosis rate of LTT cells was (30.07±2.15)% after 24 hours of mitochondrial transplantation, which was higher than 2.07±1.58 of the control group (P＜0.001). The proportion of early apoptosis in MDA-MB-468 cells was 24.47%±5.22%, which was higher than (7.83±2.06)% in the control group (P=0.007). In addition, the number of mitochondria transplanted LTT cells into the cell sphere was 46.25±5.40, which was significantly lower than 62.58±6.43 of the control group (P＜0.001). Conclusion: Normal mitochondria can enter triple-negative breast cancer cells by co-culture, inhibit the proliferation and stemness of triple-negative breast cancer cells, and promote the apoptosis of triple-negative breast cancer cells.

[Impacts of participation in surgical clinical trial on safety and survival outcomes in patients with right-sided colon cancer].

Objective: To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research. Methods: This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18-75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2-T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared. Results: The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien-Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group (Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group (Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions: A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.

[Effect of donor and recipient HLA mismatched locus on the prognosis of childhood with leukemia after umbilical cord blood transplantation].

Objective: The aim of the study was to investigate the impact of the sites of high-resolution human leukocyte antigen (HLA) mismatch on the prognosis of children with leukemia undergoing umbilical cord blood transplantation (UCBT). Methods: Clinical data and high-resolution HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 locus gene information were collected in the children who underwent the UCBT for the first time at Children's Hospital of Soochow University between January 2016 and June 2023. In each locus, according to whether the two genes were compatible, they were divided into a compatible group (two genes were perfectly matched) and a non-compatible group (one gene was not matched). In different loci, the differences in occurrence, recurrence, non-recurrence death and survival of acute graft versus host disease (aGVHD) were compared between the two groups. Multivariate Cox regression was employed to analyzed the influencing factors for overall survival rate, and Fine-Gray proportional hazards model was employed to analyze the influencing factors of other outcome events. Results: A total of 100 patients were enrolled (55 males and 45 females), whose age [M (Q1, Q3)] at the time of transplantation was 3.9 (2.0, 6.5) years. There were 55 cases in the HLA-A matched group and 45 cases in the mismatched group. The 5-year non-recurrence mortality (NRM) in the HLA-A matched group was lower than that in the mismatched group (P=0.024). The cumulative incidence of aGVHD within 100 days after transplantation in the HLA-A matched group was lower than that in the mismatched group (P=0.017), and there were no statistically significant differences in other outcome events between the groups (all P>0.05). There were 70 cases in the HLA-B matched group and 30 cases in the mismatched group. The 5-year cumulative recurrence rate in the HLA-B matched group was higher than that in the mismatched group (P=0.027). There were 79 cases in the HLA-C matched group and 21 cases in the mismatched group, and there were no statistically difference in the outcome events between the groups (P>0.05). There were 73 cases in HLA-DRB1 matched group and 27 cases in mismatched group. The 5-year overall survival rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.036), the 5-year cumulative recurrence rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.028), and the 5-year NRM in HLA-DRB1 matched group was lower than that in mismatched group (P=0.008). The cumulative incidence of aGVHD within 100 days after transplantation in the matched group was lower than that in the mismatched group (P=0.010), and and there were no statistically significant difference in other outcome events between the groups (P>0.05). There were 68 cases in HLA-DQB1 matched group and 32 cases in mismatched group. There was no statistical difference in outcome events between the two groups (all P>0.05). The risk of aGVHD in HLA-A mismatched group was higher than that in HLA-A matched group (HR=1.25, 95%CI: 1.12-1.38). The risk of recurrence in HLA-B mismatched group was lower than that in HLA-B matched group (HR=0.77, 95%CI: 0.63-0.91). Mismatched group at HLA-DRB1 compared with matched group at HLA-DRB1, had a higher risk of aGVHD (HR=1.37, 95%CI: 1.26-1.48), a higher risk of non-recurrence death (HR=1.39, 95%CI: 1.28-1.50), and a higher risk of death (HR=1.27, 95%CI: 1.18-1.36). No association was found between HLA-C and HLA-DQB1 locus with the risk of aGVHD, recurrence, non-recurrence death, and survival (all P>0.05). Conclusions: In UCBT, the risk of aGVHD in children with matching HLA-A sites of donor and recipient is lower than that in children with incompatible HLA-A sites. Compared with children with incompatible HLA-DRB1 sites, children with HLA-DRB1 matched sites has a lower risk of acute GVHD, a lower 5-year NRM, and a higher risk of death. The recurrence rate of children with matching HLA-B loci is higher than that of children without matching HLA-B loci.

[Role of intercellular adhesion molecule-1 in adhesion and migration of mesenchymal stem cells in ankylosing spondylitis and its mechanisms].

Objective: To investigate the role and underlying mechanisms of intercellular adhesion molecule-1 (ICAM-1) in the adhesion and migration of mesenchymal stem cells (MSCs) in patients with ankylosing spondylitis (AS). Methods: Bone marrow and ligament tissues were collected during surgery from patients with AS and thoracolumbar fractures (as controls, HC) treated from October 2021 to October 2022 at Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital. MSCs were isolated and cultured from the bone marrow using the Ficoll separation method. Cell morphology was observed under high-resolution microscopy, and differences in the cytoskeletal features between AS-and HC-MSCs were analyzed through immunofluorescence staining. The expression of ICAM-1 was quantified in both groups using real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. Transwell migration assays and wound healing experiments were conducted to evaluate the differences in migration rates between the two groups of MSCs. Results: The interspinous ligament and bone marrow was acquired in AS (2 males and 1 female; 33, 37, 32 years old, respectively) and no-AS patients (2 males and 1 female; 35, 32, 38 years old, respectively). AS-MSCs exhibited broader cell morphology compared to HC-MSCs under bright field and fluorescence microscopy. Immunofluorescence staining of the interspinous ligament showed higher expression of ICAM-1 (68.38±3.42 vs 48.31±2.43) and CD105 (37.97±2.16 vs 23.36±2.06) in AS patients (both P<0.001). Western blot and RT-qPCR analysis revealed significantly stronger protein expression and transcription levels of ICAM-1 in AS-MSCs when compared to those in HC-MSCs (both P<0.001). Flow cytometry confirmed greater mean fluorescence intensity of ICAM-1 in AS-MSCs than in that in HC-MSCs (924.30±54.99 vs 636.47±40.03, P=0.002). Regarding cell adhesion efficiency, it showed no significant difference between AS-MSCs and HC-MSCs in the early stage of adhesion (0.5 h: 1 496±213 vs 1 205±163, P=0.133), but they were all significantly higher in AS-MSCs in the later stage (1 h: 2 894±172 vs 1 908±155, P=0.002; 2 h: 4 540±286 vs 3 334±188, P=0.004; 3 h: 5 212±281 vs 4 208±303, P=0.014). Finally, cell migration experiments demonstrated a stronger migration capability of AS-MSCs compared to HC-MSCs (5 449±172 vs 4 016±155, P<0.001), and the inhibition efficiency of A-205804 on the migration rate of AS-MSCs was stronger than that on HC-MSCs (2 145±239 vs 3 539±316, P=0.004). Conclusions: The aberrant expression of ICAM-1 markedly influences the adhesion and migration dynamics of MSCs. Elevated ICAM-1 levels in MSCs derives from patients with AS significantly enhance their migratory capabilities.

[Histone demethylase JMJD3 inhibits alveolar bone loss by regulating macrophage polarization in periodontitis].

Objective: To investigate the expression of histone demethylase, Jumonji domain-containing protein 3 (JMJD3), in inflammatory periodontal tissues and its potential mechanism for the regulation of periodontitis. Methods: The results of single-cell sequencing of periodontal tissues published in the Gene Expression Omnibus (GEO) database in 2022 were analyzed. Nine gingival samples each from healthy and inflamed periodontal patients were collected during periodontal surgery or tooth extractions for immunohistochemical staining and real-time fluorescence quantitative PCR (RT-qPCR). Mice periodontitis models were constructed, and the experimental groups were: healthy control+saline group, silk ligation+saline group, silk ligation+GSK-J4(inhibitor of JMJD3) group. Lipopolysaccharide (LPS) derived from Porphyromonas gingivalis (Pg) (Pg-LPS) was used to mimic the periodontal inflammatory microenvironment. The macrophages were treated with small interfering RNA (siRNA) targeting Jmjd3 and the JMJD3 inhibitor GSK-J4. siRNA transfection experiments were grouped into the following: the NC group (negative control sequence transfection group), the siRNA-Jmjd3 group, the NC+LPS group, siRNA-Jmjd3+LPS group. Inhibitor experiments were grouped as dimethyl sulfoxide (DMSO) group, GSK-J4 group, DMSO+LPS group, GSK-J4+LPS group. Western blotting and immunofluorescence staining were used to explore the effects of JMJD3 on macrophage polarization and periodontal inflammation in the in vivo and in vitro settings. Results: RT-qPCR results showed that JMJD3 expression in gingival tissues of periodontitis patients (1.97±0.91) was significantly higher than that in healthy gingival tissues (1.00±0.33) (t=2.45, P=0.048). RT-qPCR results of in vitro experiments showed that either siRNA knockdown of JMJD3 or inhibition of JMJD3 using GSK-J4 promoted M1 polarization and inhibited M2 polarization in macrophages under inflammatory environment: the expression of arginase I (Arg 1) in the NC+LPS group (0.90±0.06) was significantly higher than that in the siRNA-Jmjd3+LPS group (0.61±0.11) (P<0.01); the expression of interleukin (Il)-6, Il-1ß, and tumor necrosis factor alpha (Tnf-α) in the NC+LPS group (8.50±0.16, 5.56±0.20, 3.44±0.16) were significantly lower than those in the siRNA-Jmjd3+LPS group (14.63±0.48, 8.55±0.10, 11.72±0.16) (P<0.01). The expression of Arg-1, Ym1, Il-10 in the DMSO+LPS group (0.82±0.01, 0.35±0.16, 1.47±0.11) were significantly higher (P<0.01) than the GSK-J4+LPS group (0.55±0.03, 0.22±0.21, 0.51±0.11); the expression of Il-6, Il-1ß, and Tnf-α in the DMSO+LPS group (2.03±0.13, 3.63±0.14, 4.06±0.03) were significantly lower than the GSK-J4+LPS group (2.69±0.16, 15.04±1.15, 4.36±0.10) (P<0.01). The results of the in vivo experiments revealed that inhibition of JMJD3 exacerbated bone loss in experimental periodontitis mice, increased macrophage M1 polarization, and decreased M2 polarization in inflamed periodontal tissues. The buccal cemento-enamel junction (CEJ)-alveolar bone crest (ABC), palatal CEJ-ABC, as well as the ratio of M1/M2 type macrophages were significantly lower in the silk ligation+saline group [(0.26±0.03), (0.24±0.01) mm, 0.35±0.10) than in the silk ligation+GSK-J4 group [(0.34±0.04), (0.30±0.05) mm, 2.50±0.58) (t=3.65, P=0.006; t=2.67, P=0.049; t=7.31, P=0.004; respectively). Conclusions: Single-cell sequencing as well as the in vitro and in vivo experiments verified that JMJD3 expression was upregulated in periodontitis periodontal tissues. JMJD3 may exert a protective role in periodontitis by regulating macrophage polarization, thereby inhibiting alveolar bone destruction associated with the periodontitis.

Low serum adiponectin levels are associated with an increased risk of diabetes in obese dogs.

OBJECTIVES: Adiponectin plays an important role in carbohydrate and lipid metabolism. However, the evidence regarding the association between adiponectin and diabetes mellitus in obese dogs is sparse. The aim of this study is to investigate the associations of adiponectin with the risk of diabetes mellitus in obese dogs on the basis of a prospective cohort study. MATERIALS AND METHODS: Serum adiponectin levels in obese dogs recruited from three small animal hospitals between 2015 and 2018 were measured by ELISA. Electronic health records were used to record the incidence of diabetes mellitus during follow-up for 3 years. RESULTS: A total of 862 dogs were included. Amongst the 862 dogs, 51 developed diabetes. Adiponectin levels were associated with diabetes mellitus after adjusting for sex, age, breed, exercise, body condition score, fasting plasma glucose, serum triglyceride and total cholesterol. When adjusting for sex, age, breed, exercise, body condition score, fasting plasma glucose, serum triglyceride and total cholesterol, the adjusted hazard ratios were 7.83 (95% confidence interval: 2.67 to 30.13) in the lowest adiponectin group and 1.96 (95% CI: 1.10 to 8.55) in the medium adiponectin group relative to that in the highest adiponectin group. The area under a curve of adiponectin's Receiver operating characteristic curve was 0.81 (95% CI: 0.76 to 0.86). CLINICAL SIGNIFICANCE: Low adiponectin is associated with diabetes mellitus and has a high risk of incident diabetes mellitus, implying the potential of adiponectin as a predictive biomarker of diabetes mellitus in obese dogs.

Label-free differentiation of pancreatic pathologies from normal pancreas utilizing end-to-end three-dimensional multimodal networks on CT.

AIMS: To investigate the utilization of an end-to-end multimodal convolutional model in the rapid and accurate diagnosis of pancreatic diseases using abdominal CT images. MATERIALS AND METHODS: In this study, a novel lightweight label-free end-to-end multimodal network (eeMulNet) model was proposed for the rapid and precise diagnosis of abnormal pancreas. The eeMulNet consists of two steps: pancreatic region localization and multimodal CT diagnosis integrating textual and image data. A research dataset comprising 715 CT scans with various types of pancreas diseases and 228 CT scans from a control group was collected. The training set and independent test set for the multimodal classification network were randomly divided in an 8:2 ratio (755 for training and 188 for testing). RESULTS: The eeMulNet model demonstrated outstanding performance on an independent test set of 188 CT scans (Normal: 45, Abnormal: 143), with an area under the curve (AUC) of 1.0, accuracy of 100%, and sensitivity of 100%. The average testing duration per patient was 41.04 seconds, while the classification network took only 0.04 seconds. CONCLUSIONS: The proposed eeMulNet model offers a promising approach for the diagnosis of pancreatic diseases. It can support the identification of suspicious cases during daily radiology work and enhance the accuracy of pancreatic disease diagnosis. The codes and models of eeMulNet are publicly available at Rudeguy1/eeMulNet (github.com).

[Development and evaluation of the simplified Chinese versions of motion sickness susceptibility questionnaire].

Objective: To develop and evaluate the simplified Chinese versions of motion sickness susceptibility questionnaire (MSSQ)-long (MSSQ-L) and MSSQ-short (MSSQ-S). Methods: A cross-sectional study was conducted in May 2023 among 3 426 university students at North China University of Science and Technology. The Chinese versions of MSSQ-L and MSSQ-S were distributed, and item selection for Simplified Chinese versions of MSSQ-L and MSSQ-S was performed based on item response rates, item-total correlations, Cronbach's alpha coefficients, and standard deviations. Forty-five male and forty-five female participants were recruited from the initial survey population to complete Coriolis acceleration endurance testing and fill out the simplified Chinese versions of MSSQ-L and MSSQ-S, and Graybiel symptom severity score questionnaire. Internal consistency, external consistency, criterion validity, discriminant validity, and predictive accuracy for motion sickness severity were assessed. Results: A total of 3 111 valid responses were received for the Chinese versions of MSSQ, yielding an effective response rate of 90.8% (3 111/3 426). Among the 3 111 students surveyed, there were 965 males and 2 146 females, with a mean age of (19.5±1.4) years. The highest usage rates for item were observed for cars (98.9%, 3 077/3 111) and buses (98.8%, 3 073/3 111). The simplified Chinese versions of MSSQ-L and MSSQ-S consisted of four and eight items, respectively. The Cronbach's alpha coefficients were 0.900 and 0.953 for the simplified Chinese versions of MSSQ-S and MSSQ-L, respectively, with test-retest reliabilities of 0.895 and 0.908. Criterion validity coefficients were 0.814 and 0.765 for the simplified Chinese versions of MSSQ-S and MSSQ-L, respectively. In terms of discriminant validity, significant differences were observed between mild and moderate susceptibility groups [0(0, 3) vs 6(2, 10), P=0.006] and between moderate and severe susceptibility groups [6(2, 10) vs 9(6, 13), P=0.030] for the simplified Chinese version of MSSQ-S. Significant differences were also observed between mild and moderate susceptibility groups [5(0, 3) vs 7(3, 10), P=0.001], but not between moderate and severe susceptibility groups [7(3, 10) vs 7(3, 10), P=0.081] for simplified Chinese version of MSSQ-L. The overall predictive accuracy for motion sickness severity improved from 55.6% (50/90) to 62.2% (56/90) for the simplified Chinese version of MSSQ-S and from 54.4% (49/90) to 58.9% (53/90) for the simplified Chinese version of MSSQ-L, but with no statistically significant differences (both P>0.05). Conclusions: The simplified Chinese versions of MSSQ-L and MSSQ-S demonstrates good reliability and validity. The simplified Chinese version of MSSQ-S exhibits satisfactory discriminant validity, and can serve as a simple and efficient tool for assessing motion sickness susceptibility.

[Effects of tumor location and mismatch repair on clinicopathological features and survival for non-metastatic colon cancer: A retrospective, single center, cohort study].

Objective: To analyze the differences in clinicopathological features of colon cancers and survival between patients with right- versus left-sided colon cancers. Methods: This was a retrospective cohort study. Information on patients with colon cancer from January 2016 to August 2020 was collected from the prospective registry database at Peking Union Medical College Hospital . Primary tumors located in the cecum, ascending colon, and proximal two-thirds of the transverse colon were defined as right-sided colon cancers (RCCs), whereas primary tumors located in the distal third of the transverse colon, descending colon, or sigmoid colon were defined as left-sided colon cancers (LCCs). Clinicopathological features were compared using the χ2 test or Mann-Whitney U test. Survival was estimated by Kaplan-Meier curves and the log-rank test. Factors that differed significantly between the two groups were identified by multivariate survival analyses performed with the Cox proportional hazards function. One propensity score matching was performed to eliminate the effects of confounding factors. Results: The study cohort comprised 856 patients, with TNM Stage I disease, 391 (45.7%) with Stage II, and 336 (39.3%) with Stage III, including 442 (51.6%) with LCC and 414 (48.4%) with RCC and 129 (15.1%). Defective mismatch repair (dMMR) was identified in 139 patients (16.2%). Compared with RCC, the proportion of men (274/442 [62.0%] vs. 224/414 [54.1%], χ2=5.462, P=0.019), body mass index (24.2 [21.9, 26.6] kg/m2 vs. 23.2 [21.3, 25.5] kg/m2, U=78,789.0, P<0.001), and well/moderately differentiated cancer (412/442 [93.2%] vs. 344/414 [83.1%], χ2=22.266, P<0.001) were higher in the LCC than the RCC group. In contrast, the proportion of dMMR (40/442 [9.0%] vs. 99/414 [23.9%], χ2=34.721, P<0.001) and combined vascular invasion (106/442[24.0%] vs. 125/414[30.2%], χ2=4.186, P=0.041) were lower in the LCC than RCC group. The median follow-up time for all patients was 48 (range 33, 59) months. The log-rank test revealed no significant differences in disease-free survival (DFS) (P=0.668) or overall survival (OS) (P=0.828) between patients with LCC versus RCC. Cox proportional hazards model showed that dMMR was significantly associated with a longer DFS (HR=0.419, 95%CI: 0.204‒0.862, P=0.018), whereas a higher proportion of T3-4 (HR=2.178, 95%CI: 1.089‒4.359, P=0.028), N+ (HR=2.126, 95%CI: 1.443‒3.133, P<0.001), and perineural invasion (HR=1.835, 95%CI: 1.115‒3.020, P=0.017) were associated with poor DFS. Tumor location was not associated with DFS or OS (all P>0.05). Subsequent analysis showed that RCC patients with dMMR had longer DFS than did RCC patients with pMMR (HR=0.338, 95%CI: 0.146‒0.786, P=0.012). However, the difference in OS between the two groups was not statistically significant (HR=0.340, 95%CI:0.103‒1.119, P=0.076). After propensity score matching for independent risk factors for DFS, the log-rank test revealed no significant differences in DFS (P=0.343) or OS (P=0.658) between patients with LCC versus RCC, whereas patient with dMMR had better DFS (P=0.047) and OS (P=0.040) than did patients with pMMR. Conclusions: Tumor location is associated with differences in clinicopathological features; however, this has no impact on survival. dMMR status is significantly associated with longer survival: this association may be stronger in RCC patients.

Dose-Painting Proton Radiotherapy Guided by Functional MRI in Non-enhancing High-Grade Gliomas.

AIMS: This study aimed to demonstrate the feasibility and evaluate the dosimetric effect and clinical impact of dose-painting proton radiotherapy (PRT) guided by functional MRI in non-enhancing high-grade gliomas (NE-HGGs). MATERIALS AND METHODS: The 3D-ASL and T2 FLAIR MR images of ten patients with NE-HGGs before radiotherapy were studied retrospectively. The hyperintensity on T2 FLAIR was used to generate the planning target volume (PTV), and the high-perfusion volume on 3D-ASL (PTV-ASL) was used to generate the simultaneous integrated boost (SIB) volume. Each patient received pencil beam scanning PRT and photon intensity-modulated radiotherapy (IMRT). There were five plans in each modality: (1) Uniform plans (IMRT60 vs. PRT60): 60Gy in 30 fractions to the PTV. (2)-(5) SIB plans (IMRT72, 84, 96, 108 vs. PRT72, 84, 96, 108): Uniform plan plus additional dose boost to PTV-ASL in 30 fractions to 72, 84, 96, 108 Gy. The dosimetric differences between various plans were compared. The clinical effects of target volume and organs at risk (OARs) were assessed using biological models for both tumor control probability (TCP) and normal tissue complication probability (NTCP). RESULTS: Compared with the IMRT plan, the D2 and D50 of the PRT plans with the same prescription dose increased by 1.27-4.12% and 0.64-2.01%, respectively; the R30 decreased by > 32%; the dose of brainstem and chiasma decreased by > 27% and >32%; and the dose of normal brain tissue (Br-PTV), optic nerves, eyeballs, lens, cochlea, spinal cord, and hippocampus decreased by > 50% (P < 0.05). The maximum necessary dose was 96GyE to achieve >98% TCP for PRT, and it was 84Gy to achieve >91% TCP for IMRT. The average NTCP of Br-PTV was 1.30% and 1.90% for PRT and IMRT at the maximum dose escalation, respectively. The NTCP values of the remaining OARs approached zero in all PRT plans. CONCLUSION: The functional MRI-guided dose escalation using PRT is feasible while sparing the OARs constraints and demonstrates a potential clinical benefit by improving TCP with no or minimal increase in NCTP for tissues outside the PTV. This retrospective study suggested that the use of PRT-based SIB guided by functional MRI may represent a strategy to provide benefits for patients with NE-HGGs.