Improvement in the 95-95-95 Targets Is Accompanied by a Reduction in Both the Human Immunodeficiency Virus Transmission Rate and Incidence in China.

BACKGROUND: In 2016, China has implemented the World Health Organization's "treat all" policy. We aimed to assess the impact of significant improvements in the 95-95-95 targets on population-level human immunodeficiency virus (HIV) transmission dynamics and incidence. METHODS: We focused on 3 steps of the HIV care continuum: diagnosed, on antiretroviral therapy, and achieving viral suppression. The molecular transmission clusters were inferred using HIV-TRACE. New HIV infections were estimated using the incidence method in the European Centre for Disease Prevention and Control HIV Modelling Tool. RESULTS: Between 2004 and 2023, the national HIV epidemiology database recorded 2.99 billion person-times of HIV tests and identified 1 976 878 new diagnoses. We noted a roughly "inverted-V" curve in the clustering frequency, with the peak recorded in 2014 (67.1% [95% confidence interval, 63.7%-70.5%]), concurrent with a significant improvement in the 95-95-95 targets from 10-13-<71 in 2005 to 84-93-97 in 2022. Furthermore, we observed a parabolic curve for a new infection with the vertex occurring in 2010. CONCLUSIONS: In general, it was suggested that the improvements in the 95-95-95 targets were accompanied by a reduction in both the population-level HIV transmission rate and incidence. Thus, China should allocate more effort to the first "95" target to achieve a balanced 95-95-95 target.

Trends and Patterns of HIV Transmitted Drug Resistance in China From 2018 to 2023.

BACKGROUND: National treatment guidelines of China evolving necessitates population-level surveillance of transmitted drug resistance (TDR) to inform or update HIV treatment strategies. METHODS: We analyzed the demographic, clinical, and virologic data obtained from people with HIV (PWH) residing in 31 provinces of China who were newly diagnosed between 2018 and 2023. Evidence of TDR was defined by the World Health Organization list for surveillance of drug resistance mutations. RESULTS: Among the 22 124 PWH with protease and reverse transcriptase sequences, 965 (4.36%; 95% CI, 4.1-4.63) had at least 1 TDR mutation. The most frequent TDR mutations were nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.39%; 95% CI, 2.19%-2.59%), followed by nucleoside reverse transcriptase inhibitor mutations(1.35%; 95% CI, 1.2%-1.5%) and protease inhibitor mutations (1.12%; 95% CI, .98%-1.26%). The overall protease and reverse transcriptase TDR increased significantly from 4.05% (95% CI, 3.61%-4.52%) in 2018 to 5.39% (95% CI, 4.33%-6.57%) in 2023. A low level of integrase strand transfer inhibitor TDR was detected in 9 (0.21%; 95% CI, .1%-.38%) of 4205 PWH. CONCLUSIONS: Presently, the continued use of NNRTI-based first-line antiretroviral therapy regimen for HIV treatment has been justified.

Insulin resistance is associated with the presence and severity of retinopathy in patients with type 2 diabetes.

BACKGROUND: To assess the relationship between novel insulin resistance (IR) indices and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: This is a cross-sectional study involving 2211 patients. The study outcomes were DR events. The study exposures were IR indices including estimated glucose disposal rate (eGDR), natural logarithm of glucose disposal rate (lnGDR), metabolic insulin resistance score (METS-IR), triglyceride glucose index-body mass index (TyG-BMI), triglyceride glucose index-waist-to-hip ratio (TyG-WHR), and triglyceride/high-density lipoprotein cholesterol(TG/HDL-c ratio). We used binary and multivariate ordered logistic regression models to estimate the association between different IR indices and the presence and severity of DR. Subject work characteristic curves were used to assess the predictive power of different IR indices for DR. RESULTS: DR was present in 25.4% of participants. After adjusting for all covariates, per standard deviation (SD) increases in eGDR (ratio [OR] 0.38 [95% CI 0.32-0.44]), lnGDR (0.34 [0.27-0.42]) were negatively associated with the presence of DR. In contrast, per SD increases in METS-IR (1.97 [1.70-2.28]), TyG-BMI (1.94 [1.68-2.25]), TyG-WHR (2.34 [2.01-2.72]) and TG/HDL-c ratio (1.21 [1.08-1.36]) were positively associated with the presence of DR. eGDR was strongly associated with severity of DR. Of all variables, eGDR had the strongest diagnostic value for DR (AUC = 0.757). CONCLUSIONS: Of the six IR indices, eGDR was significantly associated with the presence and severity of DR in patients with type 2 diabetes. eGDR has a good predictive value for DR. Thus, eGDR maybe a stronger marker of DR.

SARS-CoV-2 nsp5 Exhibits Stronger Catalytic Activity and Interferon Antagonism than Its SARS-CoV Ortholog.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose an enormous threat to economic activity and public health worldwide. Previous studies have shown that the nonstructural protein 5 (nsp5, also called 3C-like protease) of alpha- and deltacoronaviruses cleaves Q231 of the NF-κB essential modulator (NEMO), a key kinase in the RIG-I-like receptor pathway, to inhibit type I interferon (IFN) production. In this study, we found that both SARS-CoV-2 nsp5 and SARS-CoV nsp5 cleaved NEMO at multiple sites (E152, Q205, and Q231). Notably, SARS-CoV-2 nsp5 exhibited a stronger ability to cleave NEMO than SARS-CoV nsp5. Sequence and structural alignments suggested that an S/A polymorphism at position 46 of nsp5 in SARS-CoV versus SARS-CoV-2 may be responsible for this difference. Mutagenesis experiments showed that SARS-CoV-2 nsp5 (S46A) exhibited poorer cleavage of NEMO than SARS-CoV-2 nsp5 wild type (WT), while SARS-CoV nsp5 (A46S) showed enhanced NEMO cleavage compared with the WT protein. Purified recombinant SARS-CoV-2 nsp5 WT and SARS-CoV nsp5 (A46S) proteins exhibited higher hydrolysis efficiencies than SARS-CoV-2 nsp5 (S46A) and SARS-CoV nsp5 WT proteins in vitro. Furthermore, SARS-CoV-2 nsp5 exhibited stronger inhibition of Sendai virus (SEV)-induced interferon beta (IFN-ß) production than SARS-CoV-2 nsp5 (S46A), while introduction of the A46S substitution in SARS-CoV nsp5 enhanced suppression of SEV-induced IFN-ß production. Taken together, these data show that S46 is associated with the catalytic activity and IFN antagonism by SARS-CoV-2 nsp5. IMPORTANCE The nsp5-encoded 3C-like protease is the main coronavirus protease, playing a vital role in viral replication and immune evasion by cleaving viral polyproteins and host immune-related molecules. We showed that both SARS-CoV-2 nsp5 and SARS-CoV nsp5 cleave the NEMO at multiple sites (E152, Q205, and Q231). This specificity differs from NEMO cleavage by alpha- and deltacoronaviruses, demonstrating the distinct substrate recognition of SARS-CoV-2 and SARS-CoV nsp5. Compared with SARS-CoV nsp5, SARS-CoV-2 nsp5 encodes S instead of A at position 46. This substitution is associated with stronger catalytic activity, enhanced cleavage of NEMO, and increased interferon antagonism of SARS-CoV-2 nsp5. These data provide new insights into the pathogenesis and transmission of SARS-CoV-2.

Association between the neutrophil to lymphocyte ratio and mild cognitive impairment in patients with type 2 diabetes.

AIM: Evidence indicates that type 2 diabetes (T2D) is associated with mild cognitive impairment (MCI). Inflammation is a recognized sign of many neurodegenerative diseases. The neutrophil-to-lymphocyte ratio (NLR) is a novel and inexpensive marker of inflammation. The purpose of this study was to investigate the relationship between the NLR and MCI in patients with T2D. METHODS: The sample for this study comprised 787 patients with T2D, including 411 patients with normal cognitive function and 376 patients with MCI. Blood biochemical parameters and routine blood indicators were determined by an automatic analyzer. The NLR was calculated as the neutrophil count divided by the lymphocyte count. RESULTS: Compared with the control group, the MCI group was older and had a higher NLR but a lower education level and Montreal Cognitive Assessment (MoCA) score (p < 0.05). Spearman correlation and multiple linear regression analyses confirmed that the MoCA score was negatively associated with the NLR (p < 0.001). Multivariate logistic regression analysis demonstrated that the NLR was an independent risk factor for MCI in patients with T2D (p < 0.001). After adjusting for confounding factors, the risk of MCI for those in the third tertile of the NLR was 2.907 times higher than that of those in the first tertile of the NLR (OR = 2.907, 95%CI = 1.978-4.272, p < 0.001). CONCLUSION: An elevated NLR is associated with MCI in patients with T2D.

Effect of cement gap and drill offset on the marginal and internal fit discrepancies of crowns designed with different tooth preparations.

AIM: The aim of the present study was to evaluate the effect of cement gap and drill offset on the marginal and internal fit discrepancies of crowns designed with different tooth preparations. MATERIALS AND METHODS: Five tooth preparations were constructed, and crowns with different cement gaps and drill offsets were obtained. Then, best-fit alignment was performed on the crowns with the corresponding tooth preparations, and the fit discrepancies were expressed by color-coded difference images and root mean square (RMS) values. The RMS values of each group were analyzed by the rank-based Scheirer-Ray-Hare test (α = 0.05). RESULTS: The color segments in the sharp line angles area of the Sharp line angles group changed significantly before and after the drill offset. The cement gap had a significant effect on the marginal, internal, or overall fit discrepancies of the five design groups (P < 0.001), while the drill offset had a significant effect on the marginal fit discrepancies of the Shoulder-lip group and the internal or overall fit discrepancies of the Sharp line angles group (P < 0.001). Additionally, the interaction effect between cement gap and drill offset was significant for the marginal fit discrepancies of the Shoulder-lip group and the internal or overall fit discrepancies of the Sharp line angles group (P < 0.01). CONCLUSIONS: The cement gap and drill offset had a significant adverse effect on the marginal or internal fit discrepancies of the crowns designed with the shoulder-lip and sharp line angles designs. Tooth preparation designs with intense curvature changes such as shoulder-lip and sharp line angles should be avoided clinically.

Exosomal ncRNAs: Novel therapeutic target and biomarker for diabetic complications.

Exosomes are discoid vesicles with a diameter of 40-160 nm. They are mainly derived from the multivesicular body formed by the invagination of lysosomal particles in the cell, which are released into the extracellular matrix after the fusion of the outer membrane. Exosomes are widespread and distributed in various body fluids, they are rich in nucleic acids (microRNA, lncRNA, circRNA, mRNA, tRNA, etc.), proteins, lipids, etc. As an important mediator of cellular communication, exosomes carry and transmit important signaling molecules and are widely involved in intercellular material transport and information transfer, they regulate cellular physiological activities and are closely related to the occurrence and course of various diseases. In recent years, with the deepening of exosome-related research, we discovered that exosomal non-coding RNAs are associated with diabetic complications such as diabetic retinopathy, diabetic nephropathy, diabetic foot ulcer. This article reviews the new findings of exosomal non-coding RNAs (mainly microRNAs, lncRNAs, circRNAs) in diabetic complications, and analyzes the potential of exosomal ncRNA as new biomarkers and new cell-free therapies in the diagnosis and treatment of diabetic complications, hoping to provide new ideas for the prevention, diagnosis, and treatment of diabetic complications.

Characterization of Self-Processing Activities and Substrate Specificities of Porcine Torovirus 3C-Like Protease.

The 3C-like protease (3CLpro) of nidovirus plays an important role in viral replication and manipulation of host antiviral innate immunity, which makes it an ideal antiviral target. Here, we characterized that porcine torovirus (PToV; family Tobaniviridae, order Nidovirales) 3CLpro autocatalytically releases itself from the viral precursor protein by self-cleavage. Site-directed mutagenesis suggested that PToV 3CLpro, as a serine protease, employed His53 and Ser160 as the active-site residues. Interestingly, unlike most nidovirus 3CLpro, the P1 residue plays a less essential role in N-terminal self-cleavage of PToV 3CLpro Substituting either P1 or P4 residue of substrate alone has little discernible effect on N-terminal cleavage. Notably, replacement of the two residues together completely blocks N-terminal cleavage, suggesting that N-terminal self-cleavage of PToV 3CLpro is synergistically affected by both P1 and P4 residues. Using a cyclized luciferase-based biosensor, we systematically scanned the polyproteins for cleavage sites and identified (FXXQ↓A/S) as the main consensus sequences. Subsequent homology modeling and biochemical experiments suggested that the protease formed putative pockets S1 and S4 between the substrate. Indeed, mutants of both predicted S1 (D159A, H174A) and S4 (P62G/L185G) pockets completely lost the ability of cleavage activity of PToV 3CLpro In conclusion, the characterization of self-processing activities and substrate specificities of PToV 3CLpro will offer helpful information for the mechanism of nidovirus 3C-like proteinase's substrate specificities and the rational development of the antinidovirus drugs.IMPORTANCE Currently, the active-site residues and substrate specificities of 3C-like protease (3CLpro) differ among nidoviruses, and the detailed catalytic mechanism remains largely unknown. Here, porcine torovirus (PToV) 3CLpro cleaves 12 sites in the polyproteins, including its N- and C-terminal self-processing sites. Unlike coronaviruses and arteriviruses, PToV 3CLpro employed His53 and Ser160 as the active-site residues that recognize a glutamine (Gln) at the P1 position. Surprisingly, mutations of P1-Gln impaired the C-terminal self-processing but did not affect N-terminal self-processing. The "noncanonical" substrate specificity for its N-terminal self-processing was attributed to the phenylalanine (Phe) residue at the P4 position in the N-terminal site. Furthermore, a double glycine (neutral) substitution at the putative P4-Phe-binding residues (P62G/L185G) abolished the cleavage activity of PToV 3CLpro suggested the potential hydrophobic force between the PToV 3CLpro and P4-Phe side chains.

A novel potentiometric immunoassay for carcinoma antigen 15-3 by coupling enzymatic biocatalytic precipitation with a nanogold labelling strategy.

Methods based on potentiometric measurement have been developed for immunoassays, but most exhibit low sensitivities and are unsuitable for early diagnosis of disease. Herein we design a new potentiometric immunosensing platform for the sensitive detection of carcinoma antigen 15-3 (CA 15-3) by coupling with enzymatic biocatalytic precipitation and a nanogold labeling technique. The sandwich-type immunoreaction is carried out on a monoclonal anti-CA 15-3 capture antibody-modified working electrode, using horseradish peroxidase (HRP) and polyclonal anti-CA 15-3 detection antibody-labeled gold nanoparticles. Upon the introduction of target CA 15-3, the carried HRP molecules with an immunocomplex catalyze the oxidation of 4-chloro-1-naphthol (4-CN) into the insoluble benzo-4-chlorohexadienone. The formed product coated on the surface of the modified electrode results in a change of the electrical potential. Under optimal conditions, the shift in the electrical potential relative to the background signal increases with the increasing target CA 15-3 concentration, and exhibits a good linear relationship within the dynamic range of 0.01-30 U mL-1 at a detection limit of 7.8 mU mL-1. Good precision and reproducibility, and high specificity were acquired for the analysis of 15 human serum specimens, giving well matched results with those obtained from a human CA 15-3 ELISA kit.

[Cloning, Expression and Immungenicity Analysis of Antigen Eg-01883 Screened from Protoscoleces of Echinococcus granulosus].

Objective: To screen for the Echinococcus granulosus 01883（Eg-01883） specifically expressed at the protoscolex period, clone and express this molecule as well as analyse its immunogenicity. Methods: Eg-01883, which is highly expressed at the protoscolex period but not in oncosphere， was screened by analysing the published mRNA sequences of E. granuolosus. Total RNA of E. granuolosus was extracted, Eg-01883 was cloned by RT-PCR, and the recombinant plasmid pET28a-Eg-01883 was constructed. Expression of the recombinant protein rEg-01883 was induced by isopropyl-ß-D-thiogalactoside （IPTG）. ICR mice were randomized into 3 groups （n=12 in each group）. Mice in the immunization group received subcutaneous injections of 10 µg rEg-01883 in 100 µl PBS emulsified in Freund's adjuvant at multiple sites, followed by immune enhancement after 2 weeks. Mice in the adjuvant group were injected with PBS and adjuvant. Mice in the control group received no treatment. Blood was obtained through caudal vein before immunization, and at 1, 2, and 4 weeks after the first immunization, and through the eyeball at 6 weeks after immunization. Serum levels of IgG, IFN-γ and IL-4 were determined by ELISA. The immunogenicity of rEg-01883 was identified by Western blotting. Results: Eg-01883 was screened, cloned, expressed and purified to obtain the recombinant protein rEg-01883, which mainly existed as the inclusion body. ELISA results showed that immunization with rEg-01883 induced production of specific IgG antibody. The serum IgG level in the immunization group increased from 1 week after the first immunization, peaked at 6 weeks（2.344±0.153）, which was significantly higher than those of the adjuvant group（0.206 1±0.006） and the control group （0.241±0.01） （P<0.01）. At 6 weeks after the first immunization, the serum levels of IFN-γ （43.23 pg/ml） and IL-4（24.88 pg/ml） in the immunization group were significantly higher than those in the adjuvant group（21.77 pg/ml, 13.27 pg/ml） and the control group（17.40 pg/ml, 12.25 pg/ml）（P<0.05）. Western blot showed that the recombinant protein rEg-01883 could be recognized by His-Tag antibodies, serum of immunized mice, and serum of mice with secondary infection. Conclusion: The recombinant protein rEg-01883 shows good immunogenicity in ICR mice.

Evaluation on Surface Characteristics, Accuracy, and Dimensional Stability of Tooth Preparation Dies Fabricated by Conventional Gypsum and 3D-Printed Workflows.

PURPOSE: To evaluate the surface characteristics, accuracy (trueness and precision), and dimensional stability of tooth preparation dies fabricated using conventional gypsum and direct light processing (DLP), stereolithography (SLA), and polymer jetting printing (PJP) techniques. MATERIALS AND METHODS: Gypsum preparation dies were replicated according to the reference data and imported into DLP, SLA, and PJP printers, and the test data were obtained by scanning after 0, 1, 3, 7, 14, 28, and 42 days. After analyzing the surface characteristics, a best-fit algorithm between the test and the reference data was used to evaluate the accuracy and dimensional stability of the preparation dies. The data were analyzed by one-way analysis of variance and Tukey test or Kruskal-Wallis H test (α = .05). RESULTS: Compared with the gypsum group (3.61 ± 0.59 µm), the root mean square error (RMSE) values of the SLA group (5.33 ± 0.48 µm) was rougher (P < .05), the PJP group (2.43 ± 0.37 µm) was smoother (P < .05), and the DLP group (2.92 ± 0.91 µm) had no significant difference (P > .05). For trueness, the RMSE was greater in the PJP (34.90 ± 4.91 µm) and SLA (19.01 ± 0.95 µm) groups than in the gypsum (16.47 ± 0.47 µm) group (P < .05), and no significant difference was found between the DLP (17.10 Å} 1.77 µm) and gypsum groups. Regarding precision, the RMSE ranking was gypsum = DLP = SLA < PJP group. The RMSE ranges in the gypsum, DLP, PJP, and SLA groups at different times were 6.79 to 8.86 µm, 5.44 to 10.17 µm, 10.16 to 11.28 µm, and 10.94 to 32.74 µm, respectively. CONCLUSION: Although gypsum and printed preparation dies showed statistically significant differences in surface characteristics, accuracy, and dimensional stability, all tooth preparation dies were clinically tolerated and used to produce fixed restorations.

The Free Triiodothyronine, Gamma-Glutamyl Transpeptidase and Spontaneous Bacterial Peritonitis Index: A Novel Model for Predicting 1-Year Mortality in Patients with HBV-Related Hepatic Encephalopathy.

Background and Aims: Hepatic encephalopathy (HE) is characterized by neuropsychiatric manifestations in patients with decompensated cirrhosis (DC) and/or liver failure. This study aimed to investigate the predictive value of thyroid hormone in patients with HE. Methods: Patients with DC and HE were enrolled, and multivariate logistic analysis was conducted to analyze the risk factors for 1-year mortality. Results: Among the 81 patients with HBV-related DC and HE, 9 (11.1%) died within 3 months, and 15 (18.5%) died within the first year. More patients with FT3 < 3.5pmol/L had ascites (33.3% vs 8.9%, P<0.01) and higher model for end-stage liver disease (MELD) (Z=3.669, P<0.01). Additionally, free triiodothyronine (FT3) levels were lower in the non-survivor group (P<0.01). FT3 exhibited a negative correlation with international normalized ratio and MELD (both P<0.05). Multivariate analysis revealed that FT3, gamma-glutamyl transpeptidase (GGT), and spontaneous bacterial peritonitis (SBP) were independent risk factors for 1-year mortality of HE. A new model incorporating FT3, GTT, and SBP demonstrated superiority to MELD based on the AUROC (0.9 and 0.752, P=0.04). Conclusion: Low FT3, but not thyroid-stimulating hormone and free tetraiodothyronine, was identified as an independent risk factor for 1-year mortality in patients with DC and HE. The newly proposed prognostic model, which includes FT3, GTT, and SBP, holds significant predictive value.

RAAS in diabetic retinopathy: mechanisms and therapies.

Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR.

Adrenaline intravenous therapy persistence grade I severe allergic reaction: A case report and literature review.

RATIONALE: At present, there is still insufficient understanding of the progression from persistent allergic reactions to severe reactions. Adrenaline remains the preferred medication for severe allergic reactions, and intramuscular injection of adrenaline can also be considered for patients with grade I reactions that are difficult to alleviate gastrointestinal symptoms. It is worth further discussing whether it is possible to break the conventional intramuscular injection recommended by the guidelines when the effect of intramuscular injection is not ideal for persistent grade I severe allergic reactions. PATIENT CONCERNS: A young male, 20 years of age, was admitted to emergency department because of repeated rash for 3 days and abdominal pain for 6 hours after taking traditional Chinese medicine. After hormone therapy, the rash continued to recur and secondary gastrointestinal symptoms occurred on the 3th day. Adrenaline intramuscular injection was given to temporarily relieve the rash and abdominal pain, but symptoms still persisted. DIAGNOSIS: The patient was diagnosed with persistent severe allergic reaction (grade I). INTERVENTIONS: Continuous intravenous infusion of low-dose adrenaline under electrocardiographic monitoring, real-time monitoring of heart rate and blood pressure, and routine treatment with methylprednisolone, diphenhydramine, calcium gluconate, and cetirizine. During this period, adrenaline intramuscular injection is temporarily added when abdominal pain symptoms are obvious. The entire treatment process used a total of 6.8 mg of adrenaline. OUTCOMES: During the entire period of adrenaline intervention, the patient did not experience any new discomfort, and there were no abnormal fluctuations in heart rate, rhythm, or blood pressure. The symptoms of rash and abdominal pain gradually improved. LESSONS: For patients with persistent grade I severe allergic reactions, intravenous administration of low-dose adrenaline under close vital sign monitoring is safe, feasible, and highly effective in preventing biphasic, persistent, or worsening allergic reactions.

Splenic abscess secondary to COVID-19 acute infection: A case report and literature review.

RATIONALE: Splenic abscess is relatively rare in clinical practice as an invasive disease. However, during the continuous prevalence of coronavirus disease 2019 (COVID-19), the incidence rate of splenic abscess showed an upward trend. However, because the etiology of splenic abscess is not specific, it is easy to be covered by the respiratory symptoms of COVID-19, resulting in omission or delay in diagnosis. If splenic abscesses cannot be treated in a timely manner, the mortality rate can reach 100%. Therefore, it is important to fully understand the correlation between COVID-19 and the development of splenic abscesses. PATIENT CONCERNS: A female patient, 71 years of age, was admitted to our hospital because of cough and sputum for 1 week and fever for 2 days. According to the positive results of novel coronavirus nucleic acid and chest computed tomography, novel coronavirus pneumonia was diagnosed. On the 4th day after treatment, abdominal distension and vomiting were observed. Abdominal ultrasound indicated splenomegaly and mixed echo masses in the spleen and abdominal computed tomography indicated 2 new round low-density lesions were found in the spleen. DIAGNOSES: The patient was diagnosed with secondary splenic abscess after COVID-19 infection. INTERVENTIONS: The patient and her family members refused to undergo ultrasound-guided splenic puncture drainage and splenectomy. In terms of treatment, she was given meropenem combined with vancomycin to continue anti-infection treatment. OUTCOMES: The patient's body temperature and infection indicators gradually increased, and the scope of splenic abscess continued to expand. The infection worsened and progressed to septic shock. The patient abandoned rescue drugs and invasive treatment, and died on the 9th day after admission. LESSONS: This case introduces the clinical characteristics of secondary splenic abscess caused by COVID-19 from the aspects of etiology, disease course, clinical manifestations, auxiliary examinations, and treatment methods. The focus is on improving the understanding of clinical doctors about secondary splenic abscesses caused by COVID-19, providing reference for early diagnosis and timely treatment.

Surface modification techniques of titanium and titanium alloys for biomedical orthopaedics applications: A review.

Biomedical alloys have an important share in orthopedic applications. Among them, titanium and its titanium alloys are widely used as implant materials because of their excellent mechanical properties and non-cytotoxicity. However, its disadvantages such as its biological inertness and poor antibacterial properties inhibit its further development. Therefore, the surface properties of titanium are crucial in the implantation process and determine the success of the implant. The main purpose of this review is to provide a comprehensive and detailed description of the modification techniques used for the surface modification of titanium implants. In this paper, the corresponding technical methods are introduced systematically from four aspects: mechanical method, physical surface modification, chemical surface modification and electrochemical technique to understand the experimental mechanism of each modification technique, and the above methods can indeed improve the various properties of titanium and its alloys. With the increasing demand for implants in the future, the requirements for surface properties will also increase. Therefore, the development of new coating materials with higher performance by combining various advantages of existing modification technologies is the main trend of future research on surface modification of titanium alloys.

Effects of genus Epimedium in the treatment of osteoarthritis and relevant signaling pathways.

Osteoarthritis (OA) is a common chronic degenerative joint disease in clinical practice with a high prevalence, especially in the elderly. Traditional Chinese Medicine (TCM) believes that OA belongs to the category of "Bi syndrome" and the "bone Bi syndrome". The etiology and pathogenesis lie in the deficiency of the liver and kidney, the deficiency of Qi and blood, and external exposure to wind, cold, and dampness. Epimedium is a yang-reinforcing herb in TCM, which can tonify the liver and kidney, strengthen muscles and bones, dispel wind, cold and dampness, and can treat both the symptoms and the root cause of "bone Bi syndrome". In addition, Epimedium contains a large number of ingredients. Through modern science and technology, more than 270 compounds have been found in Epimedium, among which flavonoids are the main active ingredients. Therefore, our study will review the effects and mechanisms of genus Epimedium in treating OA from two aspects: (1) Introduction of Epimedium and its main active ingredients; (2) Effects of Epimedium and its active ingredients in treating OA and relevant signaling pathways, in order to provide more ideas for OA treatment.

[Rapid determination of five halobenzoquinones in aquatic products by QuEChERS-ultra performance liquid chromatography-tandem mass spectrometry].

Halobenzoquinones (HBQs), which are emerging chlorinated disinfection byproducts (DBPs), have attracted increasing attention because they are frequently detected in treated tap water, entrainment water, etc. These compounds are mainly generated during the water treatment process using chlorine, chloramine, and chlorine dioxide as disinfectants, and display more toxic effects than regulated DBPs, such as trihalomethane and haloacetic acid. HBQs have been recognized as potential bladder carcinogens and are harmful to the nervous system. Additionally, they can exert genotoxic effects and cause oxidative damage to DNA and proteins. The risk of HBQs in aquatic products is expected to rise because the disinfection of public facilities has significantly increased in recent years. Therefore, developing a sensitive and accurate analytical method to detect HBQs in aquatic products is of great importance. Several analytical methods, including gas chromatography, gas chromatography-mass spectrometry, electrochemical methods, liquid chromatography, and liquid chromatography-tandem mass spectrometry, can be used to identify and quantify HBQs in water. However, to the best of our knowledge, no reports on the determination of HBQ levels in aquatic products are yet available. Further, pretreatment is essential for HBQ determination because of the complex matrix effects of aquatic products. Herein, a sensitive and accurate method based on the QuEChERS technique coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of five HBQs in aquatic products. For the QuEChERS procedure, the pretreatment conditions, such as the extraction solvent and adsorbent species, were systematically optimized. The sample was extracted with 10 mL of 10% methanol acetonitrile solution (containing 0.1% formic acid), dehydrated, and centrifuged with sodium chloride and anhydrous magnesium sulfate. The supernatant was purified using a QuEChERS packing material consisting of 50 mg N-propylethylenediamine (PSA), 30 mg of graphitized carbon black (GCB), and 30 mg of neutral alumina (Al2O3), dried with nitrogen, and concentrated. The five HBQs were separated on a Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm) using 0.25% acetonitrile formate solution and 0.25% formic acid aqueous solution as the mobile phase under a gradient elution program and then detected using UPLC-MS/MS with negative electrospray ionization (ESI-) under multiple reaction monitoring (MRM) mode. Quantitative analysis was performed using a matrix-matched external standard method. The five HBQs achieved rapid separation within 6 min, indicating that the proposed method has a much shorter separation time compared with previous studies. The matrix effect was evaluated by establishing a matrix-matched calibration curve. The results showed that 2,5-dichloro-1,4-benzoquinone (2,5-DCBQ) presented a matrix-enhancing effect, whereas the other HBQs displayed matrix-inhibiting effects. In particular, tetrachlorobenzoquinone (TCBQ) exhibited strong inhibitory effects. Under the optimized experimental conditions, the five HBQs demonstrated good linear relationships in the range of 1.0-50.0 µg/L, with correlation coefficients (r)≥0.9992. The detection limits of the method were 0.15-0.8 µg/kg, and the recoveries of the target compounds were 85.9%-116.5%. The relative standard deviations were 1.4%-8.2%, which indicates good reproducibility. The proposed method was successfully applied to actual sample detection, and 2,6-dichloro-3-methyl-1,4-benzoquinone (2,6-DCMBQ) was detected in grass carp. The proposed method is convenient, sensitive, accurate, and suitable for the simultaneous determination of five HBQs in aquatic products. Moreover, the developed method provides a reliable reference for the routine monitoring of trace HBQs in food samples.

Uric acid index is a risk for mild cognitive impairment in type 2 diabetes.

BACKGROUND: A new uric acid (UA) index has recently been proposed, while serum uric acid (SUA), fasting triglyceride, and fasting blood glucose levels in the index are shown to affect cognitive function. This study aims to investigate the clinical value of the UA index for assessing mild cognitive impairment (MCI) in type 2 diabetes (T2D) patients. METHODS: This was an observational cross-sectional study with 616 participants. A generalized additive model was used to determine a linear or curvilinear relationship between cognitive performance and the UA index. Logistic regression and random forest models were both developed. A receiver operating characteristic curve (ROC) was delineated and the area under the curve (AUC) was calculated. RESULTS: MCI was diagnosed in 313 participants (50.81%). Compared with the T2D-normal cognitive function group, MCI subjects had higher UA indexes, lower cognitive scores, and lower education levels (p < 0.001). Generalized additive models showed the UA index and the Montreal Cognitive Assessment (MoCA) score to be decreased linearly (p < 0.001). The UA index AUC was 0.751 (95% CI = 0.713-0.789, p < 0.001). The optimal cut-off point for the identification of MCI based on the UA index was 11.26 (sensitivity: 62.3%, specificity: 75.9%). Results for females in the cohort yielded an AUC change of + 2.5%, the less-educated population (AUC change of + 4.7%), and the hypertensive population (AUC change of + 1.1%). The AUCs were 0.791 (95% CI = 0.720-0.863) for the random forest model and 0.804 (95% CI = 0.770-0.837) for the logistic regression model, and no statistical significance was found (p = 0.758). CONCLUSION: This study showed that the increased UA index was independently associated with MCI in patients with T2D, especially among female, less-educated, and hypertensive patients. It could be a potential indicator of MCI in T2D patients.

Zigui-Yichong-Fang protects against cyclophosphamide-induced premature ovarian insufficiency via the SIRT1/Foxo3a pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zigui-Yichong-Fang (ZGYCF) is a traditional Chinese medicine prescription for the treatment of infertility and premature ovarian insufficiency (POI). It is clinically used to regulate hormone levels, improve ovarian reserve and increase pregnancy rate. However, the exact mechanism of action is not yet clear. AIMS OF THE STUDY: This study aimed to explore the potential impact and mechanism of ZGYCF on POI, and provide a scientific basis for its clinical application. MATERIALS AND METHODS: UHPLC‒MS/MS was used to identify the main compounds of ZGYCF. Female 8-week-old C57BL/6N mice were randomized into four group containing the vehicle control (Veh) group, the cyclophosphamide (CTX) model group, the low-dose ZGYCF (CTX-ZG-L) group and the high-dose ZGYCF (CTX-ZG-H) group. A mouse POI model was induced with a single intraperitoneal injection of CTX, and the therapeutic effects of different doses of ZGYCF on POI were evaluated according to the ovarian weight coefficient, serum AMH, serum E2, ovarian histomorphology and follicle counts. After the dose screening experiment, the CTX-ZG-L group was renamed the CTX-ZG group and subjected to follow-up experiments. RNA-seq was used to explore the mechanism of POI and the therapeutic mechanism of ZGYCF on POI in Veh group, CTX group and CTX-ZG group. The mechanism of action of ZGYCF on POI were determined by measuring serum hormone level, histomorphology, follicle counts, protein expression and acetylation modification in groups of Veh, CTX, CTX-ZG and CTX-ZG-Nam (SIRT1 inhibitor). RESULTS: A total of 37 compounds in ZGYCF were identified. ZGYCF attenuated the morphological changes in ovarian tissue in POI model mice, increased serum AMH and E2 levels, reduced the damage to primordial follicles and other follicles at all stages, and protected ovarian reserve. RNA-seq results suggested that the genes expression of the PI3K signaling and apoptosis signaling pathways was increased in POI mice, while ZGYCF upregulated SIRT1 gene and the expression of estradiol, apoptosis inhibition and other signaling pathway genes. Immunohistochemical staining, TUNEL staining, Western blot analysis and immunoprecipitation results showed that in CTX group, SIRT1 expression and Foxo3a nuclei localization were decreased, while Ac-Foxo3a, p-AKT, p-Foxo3a and apoptotic markers were upregulated. After administration of ZGYCF, these conditions were reversed, however, after treatment with the SIRT1 inhibitor, the results were opposite to those of ZGYCF. CONCLUSIONS: Acetylated Foxo3a plays an important role in the occurrence of POI. ZGYCF improves the ovarian reserve of CTX-induced POI mice by activating SIRT1-mediated deacetylation of Foxo3a, and played a role in the treatment of POI. SIRT1 may be a novel target for ZGYCF to ameliorate POI.