Osteoarthritis (OA) is one of the most prevalent joint disorders, with aging considered a primary, irreversible factor contributing to its progression. Telomere-related cellular senescence may be a crucial factor influencing the OA process, yet biomarkers for OA based on telomere-related genes have not been clearly identified. The datasets GSE51588, GSE12021, and GSE55457 were retrieved from the Gene Expression Omnibus database. Initially, R software was utilized to identify differentially expressed genes between OA and normal samples. Subsequently, differentially expressed telomere-related genes (DETMRGs) were obtained, and their functional enrichment was analyzed. Feature genes for OA diagnosis were selected from DETMRGs using a combination of least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and Random Forest algorithms. The diagnostic value of these feature genes was then validated through receiver operating characteristic (ROC) curves and decision curve analysis. Additionally, CIBERSORT and xCell were employed to assess the infiltration of immune cells in OA tissues.Finally, potential drugs targeting candidate genes were predicted. Three telomererelated genes, PGD, SLC7A5, and TKT, have been identified as biomarkers for OA diagnosis and were confirmed through ROC diagnostic tests. The immune infiltration of mast cells, neutrophils, common lymphoid precursors, and eosinophils associated with PGD, SLC7A5, and TKT was reduced. Recognizing telomere-related genes PGD, SLC7A5, and TKT as potential diagnostic biomarkers for OA is significant, as it offers valuable insights into the role of telomere-related genes in OA. This discovery also provides valuable information for the diagnosis and treatment of OA.

Osteoarthritis (OA) is one of the most prevalent joint disorders, with aging considered a primary, irreversible factor contributing to its progression. Telomere-related cellular senescence may be a crucial factor influencing the OA process, yet biomarkers for OA based on telomere-related genes have not been clearly identified. The datasets GSE51588, GSE12021, and GSE55457 were retrieved from the Gene Expression Omnibus database. Initially, R software was utilized to identify differentially expressed genes between OA and normal samples. Subsequently, differentially expressed telomere-related genes (DETMRGs) were obtained, and their functional enrichment was analyzed. Feature genes for OA diagnosis were selected from DETMRGs using a combination of least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and Random Forest algorithms. The diagnostic value of these feature genes was then validated through receiver operating characteristic (ROC) curves and decision curve analysis. Additionally, CIBERSORT and xCell were employed to assess the infiltration of immune cells in OA tissues.Finally, potential drugs targeting candidate genes were predicted. Three telomererelated genes, PGD, SLC7A5, and TKT, have been identified as biomarkers for OA diagnosis and were confirmed through ROC diagnostic tests. The immune infiltration of mast cells, neutrophils, common lymphoid precursors, and eosinophils associated with PGD, SLC7A5, and TKT was reduced. Recognizing telomere-related genes PGD, SLC7A5, and TKT as potential diagnostic biomarkers for OA is significant, as it offers valuable insights into the role of telomere-related genes in OA. This discovery also provides valuable information for the diagnosis and treatment of OA.

Osteoarthritis (OA) is one of the most prevalent joint disorders, with aging considered a primary, irreversible factor contributing to its progression. Telomere-related cellular senescence may be a crucial factor influencing the OA process, yet biomarkers for OA based on telomere-related genes have not been clearly identified. The datasets GSE51588, GSE12021, and GSE55457 were retrieved from the Gene Expression Omnibus database. Initially, R software was utilized to identify differentially expressed genes between OA and normal samples. Subsequently, differentially expressed telomere-related genes (DETMRGs) were obtained, and their functional enrichment was analyzed. Feature genes for OA diagnosis were selected from DETMRGs using a combination of least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and Random Forest algorithms. The diagnostic value of these feature genes was then validated through receiver operating characteristic (ROC) curves and decision curve analysis. Additionally, CIBERSORT and xCell were employed to assess the infiltration of immune cells in OA tissues.Finally, potential drugs targeting candidate genes were predicted. Three telomererelated genes, PGD, SLC7A5, and TKT, have been identified as biomarkers for OA diagnosis and were confirmed through ROC diagnostic tests. The immune infiltration of mast cells, neutrophils, common lymphoid precursors, and eosinophils associated with PGD, SLC7A5, and TKT was reduced. Recognizing telomere-related genes PGD, SLC7A5, and TKT as potential diagnostic biomarkers for OA is significant, as it offers valuable insights into the role of telomere-related genes in OA. This discovery also provides valuable information for the diagnosis and treatment of OA.

Osteoarthritis (OA) is one of the most prevalent joint disorders, with aging considered a primary, irreversible factor contributing to its progression. Telomere-related cellular senescence may be a crucial factor influencing the OA process, yet biomarkers for OA based on telomere-related genes have not been clearly identified. The datasets GSE51588, GSE12021, and GSE55457 were retrieved from the Gene Expression Omnibus database. Initially, R software was utilized to identify differentially expressed genes between OA and normal samples. Subsequently, differentially expressed telomere-related genes (DETMRGs) were obtained, and their functional enrichment was analyzed. Feature genes for OA diagnosis were selected from DETMRGs using a combination of least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and Random Forest algorithms. The diagnostic value of these feature genes was then validated through receiver operating characteristic (ROC) curves and decision curve analysis. Additionally, CIBERSORT and xCell were employed to assess the infiltration of immune cells in OA tissues.Finally, potential drugs targeting candidate genes were predicted. Three telomererelated genes, PGD, SLC7A5, and TKT, have been identified as biomarkers for OA diagnosis and were confirmed through ROC diagnostic tests. The immune infiltration of mast cells, neutrophils, common lymphoid precursors, and eosinophils associated with PGD, SLC7A5, and TKT was reduced. Recognizing telomere-related genes PGD, SLC7A5, and TKT as potential diagnostic biomarkers for OA is significant, as it offers valuable insights into the role of telomere-related genes in OA. This discovery also provides valuable information for the diagnosis and treatment of OA.

Osteoarthritis (OA) is one of the most prevalent joint disorders, with aging considered a primary, irreversible factor contributing to its progression. Telomere-related cellular senescence may be a crucial factor influencing the OA process, yet biomarkers for OA based on telomere-related genes have not been clearly identified. The datasets GSE51588, GSE12021, and GSE55457 were retrieved from the Gene Expression Omnibus database. Initially, R software was utilized to identify differentially expressed genes between OA and normal samples. Subsequently, differentially expressed telomere-related genes (DETMRGs) were obtained, and their functional enrichment was analyzed. Feature genes for OA diagnosis were selected from DETMRGs using a combination of least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and Random Forest algorithms. The diagnostic value of these feature genes was then validated through receiver operating characteristic (ROC) curves and decision curve analysis. Additionally, CIBERSORT and xCell were employed to assess the infiltration of immune cells in OA tissues.Finally, potential drugs targeting candidate genes were predicted. Three telomererelated genes, PGD, SLC7A5, and TKT, have been identified as biomarkers for OA diagnosis and were confirmed through ROC diagnostic tests. The immune infiltration of mast cells, neutrophils, common lymphoid precursors, and eosinophils associated with PGD, SLC7A5, and TKT was reduced. Recognizing telomere-related genes PGD, SLC7A5, and TKT as potential diagnostic biomarkers for OA is significant, as it offers valuable insights into the role of telomere-related genes in OA. This discovery also provides valuable information for the diagnosis and treatment of OA.

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.
Male ; Child ; Female ; Humans ; Child, Preschool ; Receptors, Tumor Necrosis Factor, Type I/genetics* ; Retrospective Studies ; Hereditary Autoinflammatory Diseases/drug therapy* ; Glucocorticoids/therapeutic use* ; Biological Factors/therapeutic use* ; Immunosuppressive Agents/therapeutic use* ; Autoantibodies ; Familial Mediterranean Fever/diagnosis* ; Mutation

This study evaluated the scientific nature and effectiveness of iterative optimization of prevention and control measures for local outbreaks caused by the BA.2 and BA.5.2 COVID-19 strains in Fujian Province in 2022,to provide a scientif-ic basis for responding to future new or recurrent respiratory infectious diseases.According to the theory of infectious disease dynamics,relevant information regarding the local epidemic situation caused by the BA.2 sub-type Omicron virus strain in March 2022 and BA.5.2 sub-type Omicron virus strain in October 2022 in Fujian Province was collected.The susceptible exposed infectious removed(SEIAR)model of COVID-19 infection with a latent period and asymptomatic infected persons was used to analyze the transmission dynam-ics of two local epidemic situations,and evaluate the preven-tion and control effects.The incubation period of the BA.2 epidemic was 3 days(1～9 days),the intergenerational inter-val was 3 days(1～5 days),and the initial Rt was 3.0(95％CI:2.7～3.3).The incubation period of the BA.5.2 epidemic was 2 days(1～6 days),the intergenerational interval was 1 day(0～2 days),and the initial R,was 1.9(95％CI:1.7～2.1).The fittingresults for the BA.2 and BA.5.2 epidemics were good,and no statistical difference was observed between the predic-ted and actual numbers of cases(x2BA.2=31.53,x2BA.5.2=27.88,P＞0.05).If an emergency response had not been initiated,the BA.2 epidemic would have continued to spread andpeak on April 7th,with an estimated 638 035 cases.The BA.5.2 epidemic would have rapidly spread,reaching a peak on November 14th,with an estimated 685 940 cases.If one incubation period were detected early,the scale of the BA.2 epidemic would have decreased by 25.73％;if two incubation periods were detected early,the scale would have decreased by 79.56％,and if one incubation period had been delayed,the scale would have expanded by 13.72％.If one incubation period had been detected early in the BA.5.2 epidemic,the scale would have decreased by 35.04％;if two incubation periods had been detected early,the scale would have decreased by 92.47％;and if one incubation period had been delayed,the scale would have increased by 19.75％.The guiding ideology,and the prevention and control measures for handling two local epidemics were optimized and iterated.Our study indicated that implementing the"four early"measures ef-fectively decreased the scale of the epidemic,and earlier detection was associated with more significant control effects.This study provides valuable information for the prevention and control of new or recurrent respiratory infectious diseases.

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.
Humans ; Bacteremia/epidemiology* ; Cefoperazone ; Sulbactam ; Retrospective Studies ; Drug Resistance, Bacterial ; Microbial Sensitivity Tests ; Hematologic Neoplasms ; Sepsis ; Anti-Bacterial Agents/pharmacology* ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Piperacillin, Tazobactam Drug Combination ; Escherichia coli

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Neoplasms/pathology* ; Thrombocytopenia/drug therapy* ; Treatment Outcome ; Adult ; Aged

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis