Huangqin decoction attenuates spared nerve injury (SNI)-induced neuropathic pain by modulating microglial M1/M2 polarization partially mediated by intestinal nicotinamide metabolism.

BACKGROUND: The incidence of neuropathic pain is progressively increasing over time. The activation of M1-type microglia plays a crucial role in the initiation and progression of neuropathic pain. Huangqin Decoction (HQD) is traditionally used to alleviate dysentery and abdominal pain. However, it remains unclear whether HQD can effectively mitigate neuropathic pain and the underlying mechanisms. PURPOSE: The present study aims to investigate the impact of HQD on neuropathic pain induced by spared nerve injury (SNI) in mice, and to elucidate whether the analgesic effect of HQD is associated with microglia polarization. METHODS: The analgesic effect of HQD on SNI mice was investigated through assessments of mechanical pain threshold, thermal pain threshold, cold pain threshold, and motor ability. We elucidated the molecular mechanisms of HQD in alleviating SNI-induced neuropathic pain by focusing on microglia polarization and intestinal metabolite abnormalities. The expression levels of markers associated with microglia polarization (Iba-1, CD68, CD206, iNOS) was detected by immunofluorescence and Western blot, and the levels of inflammatory factors (IL-4, IL-10, IL-6, TNF-α) were assessed by ELISA. UPLC-QTOF-MS metabolomics was utilized to identify differential metabolites in the intestines of SNI mice. We screened the differential metabolites related to microglial polarization by correlation analysis, subsequently nicotinamide was selected for validation in LPS-induced BV-2 cells. RESULTS: Our findings demonstrated that HQD (20 g/kg) significantly enhanced the mechanical pain threshold, thermal pain threshold, and cold pain threshold, and protected the injured DRG neurons of SNI mice. Moreover, HQD (20 g/kg) obviously suppressed the expression of microglia M1 polarization markers (Iba-1, CD68, iNOS, IL-6, TNF-α), and promoted the expression of microglia M2 polarization markers (CD206, IL-10, IL-4) in the spinal cord of SNI mice. Additionally, HQD (20 g/kg) prominently ameliorated intestinal barrier damage by upregulating Claudin 1 and Occludin expression in the colon of SNI mice. Furthermore, HQD (20 g/kg) rectified 19 metabolite abnormalities in the intestine. Notably, nicotinamide (100 µM), an amide derivative with anti-inflammatory property, effectively suppresses microglia activation and polarization in LPS-induced BV-2 cells by downregulating IL-6 level and CD68 expression while upregulating IL-4 level and CD206 expression. CONCLUSION: In summary, HQD alleviates neuropathic pain in SNI mice by regulating the activation and polarization of microglia, partially mediated through intestinal nicotinamide metabolism.

A responsive disulfide bond switch aptamer prodrug exhibiting enhanced stability and anticancer efficacy.

Aptamers have shown significant potential in treating diverse diseases. However, challenges such as stability and drug delivery limited their clinical application. In this paper, the development of AS1411 prodrug-type aptamers for tumor treatment was introduced. A Short oligonucleotide was introduced at the end of the AS1411 sequence with a disulfide bond as responsive switch. The results indicated that the aptamer prodrugs not only enhanced the stability of the aptamer against nuclease activity but also facilitated binding to serum albumin. Furthermore, in the reducing microenvironment of tumor cells, disulfide bonds triggered drug release, resulting in superior therapeutic effects in vitro and in vivo compared to original drugs. This paper proposes a novel approach for optimizing the structure of nucleic acid drugs, that promises to protect other oligonucleotides or secondary structures, thus opening up new possibilities for nucleic acid drug design.

Research progress in photodynamic therapy for Helicobacter pylori infection.

Helicobacter pylori (H. pylori) is a pathogenic microorganism that colonizes the human gastric mucosa and can lead to various gastric disorders, including gastritis, gastric ulcers, and gastric cancer. However, the increasing prevalence of antibiotic resistance in H. pylori has prompted the search for alternative treatment options. Photodynamic therapy has emerged as a potential alternative therapy, thus offering the advantage of avoiding some of the side effects associated with antibiotics and effectively targeting drug-resistant strains. In the postantibiotic era, photodynamic therapy (PDT) has shown promise as a novel treatment for H. pylori infection. This review focused on elucidating the mechanism of photodynamic therapy in the treatment of H. pylori. Additionally, we present an overview of the current research on photodynamic therapy by examining both standalone photodynamic therapy and combination therapies for H. pylori infection treatment. Furthermore, the safety profile of photodynamic therapy was also evaluated. Finally, we discuss the challenges and prospects associated with this innovative technology, with an aim to provide new insights and methodologies for the treatment of H. pylori infection.

Trends of type 2 diabetes with pulmonary tuberculosis patients,2013-2022, and changes after the coronavirus disease 2019 (COVID-19) pandemic.

BACKGROUND: To describe the trends of Type 2 Diabetes with Pulmonary Tuberculosis (T2DM-TB) patients from 2013 to 2022 and to investigate the impact of COVID-19 lockdown on glycemic control and associated factors in T2DM-TB. METHODS: In this population-based study of the First Affiliated Yijishan Hospital of Wannan Medical College in China, we described the 10-year trends of patients diagnosed with T2DM-TB. We included patients diagnosed with TB, T2DM-TB and T2DM-TB patients for comparative analysis, aged 15 years or older. Data were missing, and both multidrug-resistant (MDR) TB patients and non-T2DM patients were excluded from our study. RESULTS: We pooled Type 2 Diabetes (T2DM) and Tuberculosis (TB) data from The First Affiliated Yijishan Hospital of Wannan Medical College in China, gathered between January 1, 2013, and December 31, 2022. The data included 14,227 T2DM patients, 6130 TB patients, and 982 T2DM-TB patients. During the past 10 years, the number of inpatients with TB decreased, while the number of patients with T2DM and T2DM-TB increased year by year. To rule out any influence factors, we analyzed the ratio of the three groups. The ratio of TB/T2DM decreased year by year (p < 0.05), while the ratio of TB-T2DM/TB increasing year by year (p = 0.008). During the COVID-19 epidemic period, there was no significant change in the ratio of TB-T2DM/T2DM (p = 0.156). There was no significant change in the proportion of male patients with TB and TB-T2DM (p = 0.325; p = 0.190), but the proportion of male patients with T2DM showed an increasing trend (p < 0.001). The average age of TB patients over the past 10 years was 54.5 ± 18.4 years and showed an increasing trend year by year (p < 0.001). However, there was no significant change in the age of T2DM or TB-T2DM patients (p = 0.064; p = 0.241). Patients data for the first (2013-2017) and the last (2018-2022) five years were compared. We found that the number of T2DM and TB-T2DM in the last five years was significantly higher than in the first five years, but the number of TB was significantly lower than in the first five years. There is a significant statistical difference in the proportion of TB/T2DM and TB-T2DM/TB, which is similar to the previous results. The average age (56.0 ± 17.6 years) of TB patients in the last five years is significantly higher than in the first five years (53.1 ± 18.9) (p < 0.001). The number of male patients with T2DM in the last five years is higher than that in the first five years, with significant difference (p < 0.001). CONCLUSION: The trends of T2DM-TB among hospitalized TB patients have increased significantly over the past 10 years, which may be related to the increase in the number of T2DM cases. The COVID-19 pandemic has been effective in controlling the transmission of TB, but it has been detrimental to the control of T2DM. Male patients with T2DM and elderly TB patients are the key populations for future prevention and control efforts.

Immune-Enhancing Treatment among Acute Necrotizing Pancreatitis Patients with Metabolic Abnormalities: A Post Hoc Analysis of a Randomized Clinical Trial.

Background/Aims: : Metabolic syndrome is common in patients with acute pancreatitis and its components have been reported to be associated with infectious complications. In this post hoc analysis, we aimed to evaluate whether metabolic abnormalities impact the effect of immune-enhancing thymosin alpha-1 (Tα1) therapy in acute necrotizing pancreatitis (ANP) patients. Methods: : All data were obtained from the database for a multicenter randomized clinical trial that evaluated the efficacy of Tα1 in ANP patients. Patients who discontinued the Tα1 treatment prematurely were excluded. The primary outcome was 90-day infected pancreatic necrosis (IPN) after randomization. Three post hoc subgroups were defined based on the presence of hyperglycemia, hypertriglyceridemia, or both at the time of randomization. In each subgroup, the correlation between Tα1 and 90-day IPN was assessed using the Cox proportional-hazards regression model. Multivariable propensity-score methods were used to control potential bias. Results: : Overall, 502 participants were included in this post hoc analysis (248 received Tα1 treatment and 254 received matching placebo treatment). Among them, 271 (54.0%) had hyperglycemia, 371 (73.9%) had hypertriglyceridemia and 229 (45.6%) had both. Tα1 therapy was associated with reduced incidence of IPN among patients with hyperglycemia (18.8% vs 29.7%: hazard ratio, 0.80; 95% confidence interval, 0.37 to 0.97; p=0.03), but not in the other subgroups. Additional multivariate regression models using three propensity-score methods yielded similar results. Conclusions: : Among ANP patients with hyperglycemia, immune-enhancing Tα1 treatment was associated with a reduced risk of IPN (ClinicalTrials.gov, Registry number: NCT02473406).

Degradation of refractory organic matter in MBR effluent from treating landfill leachate by UV/PMS and UV/H2O2: a comparative study.

This study applied ultraviolet/peroxymonosulfate (UV/PMS) and UV/hydrogen peroxide (UV/H2O2) processes to the advanced treatment of membrane bioreactor (MBR) effluent. The degradation efficiency of refractory organic matter and the reaction mechanisms of the two processes were systematically investigated. The results showed that the degradation efficiency of the UV/PMS processes was significantly lower than that of the UV/H2O2 process when the PMS concentration was significantly lower than the H2O2 concentration, e.g. the UV254 removals under optimal conditions were 72.92% and 82.21%, respectively. Additionally, the UV/PMS process could operate over a broader pH range. The degradation efficiency of the UV/PMS process was slightly increased by HCO3- and Cl- due to the activation of PMS, while in the UV/H2O2 process, HCO3- and Cl- depressed the degradation efficiency by competing with organic matter to react with reactive oxygen species (ROS). After the two processes, the aromaticity, humification, condensation degree, and molecular weight of refractory organic matter in the MBR effluent were considerably decreased. Fulvic- (HA) and humic-like substances (FA) were greatly degraded by the two processes. The UV/PMS had a superior degradation efficiency for macromolecular HA in the early stage of the reaction, and the UV/H2O2 could degrade HA to protein-like substances in the latter stage of the reaction. These differences between the two processes could be attributed to the dominance of different ROS, with SO4•- and HO• dominating in the UV/PMS, and HO• dominating in the UV/H2O2. The results of this study provide theoretical support for the application of MBR effluent treatment.Highlights Comparison on the MBR effluent treatment of UV/PMS and UV/H2O2 is studied.UV/PMS process can better destroy humic-like substances in the early reaction stage.Humic-like substances are transformed into protein-like compounds in UV/H2O2 process.UV/PMS and UV/PMS performs differently due to their different dominant ROS.

PTPN1 is a prognostic biomarker related to cancer immunity and drug sensitivity: from pan-cancer analysis to validation in breast cancer.

Background: Protein tyrosine phosphatase non-receptor type 1 (PTPN1), a member of the protein tyrosine phosphatase superfamily, has been identified as an oncogene and therapeutic target in various cancers. However, its precise role in determining the prognosis of human cancer and immunological responses remains elusive. This study investigated the relationship between PTPN1 expression and clinical outcomes, immune infiltration, and drug sensitivity in human cancers, which will improve understanding regarding its prognostic value and immunological role in pan-cancer. Methods: The PTPN1 expression profile was obtained from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia databases. Kaplan-Meier, univariate Cox regression, and time-dependent receiver operating characteristic curve analyses were utilized to clarify the relationship between PTPN1 expression and the prognosis of pan-cancer patients. The relationships between PTPN1 expression and the presence of tumor-infiltrated immune cells were analyzed using Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data and Tumor Immune Estimation Resource. The cell counting kit-8 (CCK-8) assay was performed to examine the effects of PTPN1 level on the sensitivity of breast cancer cells to paclitaxel. Immunohistochemistry and immunoblotting were used to investigate the relationship between PTPN1 expression, immune cell infiltration, and immune checkpoint gene expression in human breast cancer tissues and a mouse xenograft model. Results: The pan-cancer analysis revealed that PTPN1 was frequently up-regulated in various cancers. High PTPN1 expression was associated with poor prognosis in most cancers. Furthermore, PTPN1 expression correlated highly with the presence of tumor-infiltrating immune cells and the expression of immune checkpoint pathway marker genes in different cancers. Furthermore, PTPN1 significantly predicted the prognosis for patients undergoing immunotherapy. The results of the CCK-8 viability assay revealed that PTPN1 knockdown increased the sensitivity of MDA-MB-231 and MCF-7 cells to paclitaxel. Finally, our results demonstrated that PTPN1 was associated with immune infiltration and immune checkpoint gene expression in breast cancer. Conclusion: PTPN1 was overexpressed in multiple cancer types and correlated with the clinical outcome and tumor immunity, suggesting it could be a valuable potential prognostic and immunological biomarker for pan-cancer.

Combined use of total glucosides of paeony and hydroxychloroquine in primary Sjögren's syndrome: A systematic review.

OBJECTIVE: To assess the effectiveness and safety of the total glucosides of paeony (TGP) combined with hydroxychloroquine (HCQ) on the treatment of primary Sjögren's syndrome (pSS) by conducting a meta-analysis. METHODS: Eight databases were searched for randomized controlled trials (RCTs) reporting the use of TGP combined with HCQ for pSS, which are before May 10, 2022. Meta-analyses were performed on disappeared clinical symptoms (dry mouth and dry eyes), Schirmer's test, saliva flow test, erythrocyte sedimentation rate (ESR), index of immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), and adverse events (AEs). The Revman 5.4 software was used for this meta-analysis. RESULTS: Seven RCTs which included 632 participants were identified. The pooled results showed significant differences in clinical symptoms disappear (dry mouth and dry eyes) (p = .0004), IgM (p < .00001), IgA (p < .00001), salivary flow rate (p < .00001) and Schirmer's test (p = .02) in the comparison of TGP combined with HCQ and HCQ alone. For the IgG and ESR, both pooled and subgroup analyses showed that TGP + HCQ was superior to HCQ alone. For the safety analysis, no significant differences in AEs (p = .39) was revealed. The more frequently seen adverse reactions were diarrhea, vomit and there was no severe adverse events were reported in TGP + HCQ group. CONCLUSION: Therefore, TGP + HCQ can be considered to be a potentially valid and safe combination for the treatment of pSS in the clinic.

Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study.

Corona virus disease 2019 (COVID-19) is prone to induce multiple organ damage. The kidney is one of the target organs of SARS-CoV-2, which is susceptible to inducing acute kidney injury (AKI). Huanglian Jiedu Decoction (HLJDD) is one of the recommended prescriptions for COVID-19 with severe complications. We used network pharmacology and molecular docking to explore the therapeutic and protective effects of HLJDD on COVID-19-associated AKI. Potential targets related to "HLJDD," "COVID-19," and "Acute Kidney Injury/Acute Renal Failure" were identified from several databases. A protein-protein interaction (PPI) network was constructed and screened the core targets according to the degree value. The target genes were then enriched using gene ontology and Kyoto Encyclopedia of Genes and Genomes. The bioactive components were docked with the core targets. A total of 65 active compounds, 85 common targets for diseases and drugs were obtained; PPI network analysis showed that the core protein mainly involved JUN, RELA, and AKT1; functional analysis showed that these target genes were mainly involved in lipid and atherosclerosis signaling pathway and IL-17 signal pathway. The results of molecular docking showed that JUN, RELA, and AKT1 had good binding activity with the effective chemical components of HLJDD. In conclusion, HLJDD can be used as a potential therapeutic drug for COVID-19-associated AKI.

Molecular and Phenotypic Changes in FLExDUX4 Mice.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the double homeobox 4 (DUX4) gene. The FLExDUX4 mouse model carries an inverted human DUX4 transgene which has leaky DUX4 transgene expression at a very low level. No overt muscle pathology was reported before 16 weeks. The purpose of this study is to track and characterize the FLExDUX4 phenotypes for a longer period, up to one year old. In addition, transcriptomic changes in the muscles of 2-month-old mice were investigated using RNA-seq. The results showed that male FLExDUX4 mice developed more severe phenotypes and at a younger age in comparison to the female mice. These include lower body and muscle weight, and muscle weakness measured by grip strength measurements. Muscle pathological changes were observed at older ages, including fibrosis, decreased size of type IIa and IIx myofibers, and the development of aggregates containing TDP-43 in type IIb myofibers. Muscle transcriptomic data identified early molecular changes in biological pathways regulating circadian rhythm and adipogenesis. The study suggests a slow progressive change in molecular and muscle phenotypes in response to the low level of DUX4 expression in the FLExDUX4 mice.

Fueling sentinel node via reshaping cytotoxic T lymphocytes with a flex-patch for post-operative immuno-adjuvant therapy.

Clinical updates suggest conserving metastatic sentinel lymph nodes (SLNs) of breast cancer (BC) patients during surgery; however, the immunoadjuvant potential of this strategy is unknown. Here we leverage an immune-fueling flex-patch to animate metastatic SLNs with personalized antitumor immunity. The flex-patch is implanted on the postoperative wound and spatiotemporally releases immunotherapeutic anti-PD-1 antibodies (aPD-1) and adjuvants (magnesium iron-layered double hydroxide, LDH) into the SLN. Genes associated with citric acid cycle and oxidative phosphorylation are enriched in activated CD8+ T cells (CTLs) from metastatic SLNs. Delivered aPD-1 and LDH confer CTLs with upregulated glycolytic activity, promoting CTL activation and cytotoxic killing via metal cation-mediated shaping. Ultimately, CTLs in patch-driven metastatic SLNs could long-termly maintain tumor antigen-specific memory, protecting against high-incidence BC recurrence in female mice. This study indicates a clinical value of metastatic SLN in immunoadjuvant therapy.

A smartphone-assisted colorimetric and photothermal probe for glutathione detection based on enhanced oxidase-mimic CoFeCe three-atom nanozyme in food.

The rational fabrication of point-of-care testing (POCT) featuring simplicity, rapidity, low cost, portability, high sensitivity and accuracy is crucial for maintaining food safety in resource-limited locations and home healthcare but remains challenging. Herein, we report a universal colorimetric-photothermal-smartphone triple-mode sensing platform for POC food-grade glutathione (GSH) detection. This simple sensing platform for GSH detection takes merits of three techniques: commercially available filter paper, thermometer and smartphone via an excellent CoFeCe-mediated oxidase-like activity. This strategy allows CoFeCe three-atom hydroxide to efficiently convert dissolved oxygen into O2·- and catalyzes 3, 3', 5, 5'-tertamethylbenzidine (TMB) to generate an oxidized TMB with remarkable color changes and photothermal effect, resulting in a colorimetric-temperature-color triple-mode signal output. The constructed sensor exhibits high sensitivity with a limit of detection of 0.092 µM for GSH detection. We expect this sensing platform can be easily modified for the determination of GSH in commercial samples with the simple testing strips.

Dual-mode biosensor platform based on synergistic effects of dual-functional hybrid nanomaterials.

Detection of biomarkers is very vital in the prevention, diagnosis and treatment of diseases. However, due to the poor accuracy and sensitivity of the constructed biosensors, we are now facing great challenges. In addressing these problems, nanohybrid-based dual mode biosensors including optical-optical, optical-electrochemical and electrochemical-electrochemical have been developed to detect various biomarkers. Integrating the merits of nanomaterials with abundant active sites, synergy and excellent physicochemical properties, many bi-functional nanohybrids have been reasonable designed and controllable preparation, which applied to the construction dual mode biosensors. Despite the significant progress, further efforts are still needed to develop dual mode biosensors and ensure their practical application by using portable digital devices. Therefore, the present review summarizes an in-depth evaluation of the bi-functional nanohybrids assisted dual mode biosensing platform of biomarkers. We are hoping this review could inspire further concepts in developing novel dual mode biosensors for possible detection application.

SB Digestor: a tailored driver gene identification tool for dissecting heterogeneous Sleeping Beauty transposon-induced tumors.

Sleeping Beauty (SB) insertional mutagenesis has been widely used for genome-wide functional screening in mouse models of human cancers, however, intertumor heterogeneity can be a major obstacle in identifying common insertion sites (CISs). Although previous algorithms have been successful in defining some CISs, they also miss CISs in certain situations. A major common characteristic of these previous methods is that they do not take tumor heterogeneity into account. However, intertumoral heterogeneity directly influences the sequence read number for different tumor samples and then affects CIS identification. To precisely detect and define cancer driver genes, we developed SB Digestor, a computational algorithm that overcomes biological heterogeneity to identify more potential driver genes. Specifically, we define the relationship between the sequenced read number and putative gene number to deduce the depth cutoff for each tumor, which can reduce tumor complexity and precisely reflect intertumoral heterogeneity. Using this new tool, we re-analyzed our previously published SB-based screening dataset and identified many additional potent drivers involved in Brca1-related tumorigenesis, including Arhgap42, Tcf12, and Fgfr2. SB Digestor not only greatly enhances our ability to identify and prioritize cancer drivers from SB tumors but also substantially deepens our understanding of the intrinsic genetic basis of cancer.

Degradation of refractory organic matter in MBR effluent from treating landfill leachate by the UV-nZVI-H2O2 system.

In this study, nano zero-valent iron (nZVI) was used as the Fe2+ source in the Fenton reaction, and a UV-nZVI-H2O2 system was constructed to efficiently degrade and mineralize refractory organic matter in landfill leachate. The results showed that under the optimal conditions (initial pH = 3, UV = 14 W, nZVI = 0.5 g/L, and [H2O2] = 30 mM), the removal efficiencies of total organic carbon, absorbance at 254 nm, and color number were 61.38%, 83.89%, and 85.79%, respectively. Control experiments show that the UV-nZVI-H2O2 system has the highest removal rate and mineralization rate of refractory organic matter. The excellent performance of the UV-nZVI-H2O2 system is related to a higher H2O2 utilization rate. The H2O2 residue in the UV-nZVI-H2O2 system was the lowest, and the effective utilization rate of H2O2 was as high as 98.80%. Alcohol quenching experiments and hydroxyl radical quantitative experiments showed that the dominant reactive oxygen species in the UV-nZVI-H2O2 system was HO• and the yield of HO• was as high as 2007.80 µM, which was much higher than that in other systems. The results of spectra analysis showed that the low molecular weight, high fluorescence frequency organic matter, and relatively stable aromatic organic matter were significantly degraded after treatment with the UV-nZVI-H2O2 system and the aromatic degree, humification degree, molecular weight, and molecular polymerization degree of refractory organic matter were also significantly decreased. The mechanism of the UV-nZVI-H2O2 reaction includes homogeneous and heterogeneous Fenton reactions and adsorption and precipitation of organic matter by iron-based colloids. This study can provide theoretical and technical support for the advanced treatment of refractory organic matter in landfill leachate.

Schiff base cross-linked dialdehyde cellulose/gelatin composite aerogels as porous structure templates for oleogels preparation.

Recently, biopolymer-based structured oil has emerged to substitute saturated and trans-fats. Herein, the porous biopolymeric networks with the cellular structure were developed with cross-linked dialdehyde cellulose (DAC) and gelatin to prepare oleogels. The determination of aldehyde content in the DAC molecular chain revealed a high degree of oxidation of cellulose. The FTIR data showed the covalent cross-linking bond between the DAC and gelatin. The covalent cross-linking between DAC and gelatin promoted the composite aerogel (DG) to form a porous three-dimensional network structure with enhanced thermal stability, mechanical properties, and water stability. The DAC/gelatin composite aerogel with 5 wt% DAC (DG-5) exhibited the highest porosity (91.27 %) and lowest pore diameter (10.52 µm) with greater capillary force, resulting in a high oil absorption capacity of 11.24 g/g and oil holding capacity of 55.57 %. The DG oleogels containing 6 % thymol in the oil phase showed good antibacterial activities against Escherichia coli and Staphylococcus aureus for 24 h. This work provides a facile and promising strategy for developing oleogels by DAC/gelatin cross-linked conjugates as aerogel templates for oil structuring.

Modeling methods for busulfan-induced oligospermia and asthenozoospermia in mice: a systematic review and meta-analysis.

OBJECTIVE: Modeling methods for busulfan-induced oligoasthenozoospermia are controversial. We aimed to systematically review the modeling method of busulfan-induced oligospermia and asthenozoospermia, and analyze changes in various evaluation indicators at different busulfan doses over time. METHODS: We searched the Cochrane Library, PubMed databases, Web of Science, the Chinese National Knowledge Infrastructure, and the Chinese Biomedical Literature Service System until April 9, 2022. Animal experiments of busulfan-induced spermatogenesis dysfunction were included and screened. The model mortality and parameters of the evaluation indicators were subjected to meta-analysis. RESULTS: Twenty-nine animal studies were included (control/model: 669/1829). The mortality of mice increased with busulfan dose. Significant spermatogenesis impairment occurred within 5 weeks, regardless of busulfan dose (10-40 mg/kg). Testicular weight (weighted mean difference [WMD]: - 0.04, 95% CI: - 0.05, - 0.03), testicular index (WMD: - 2.10, 95% CI: - 2.43, - 1.76), and Johnsen score (WMD: - 4.67, 95% CI: - 5.99, - 3.35) were significantly decreased. The pooled sperm counts of the model group were reduced by 32.8 × 106/ml (WMD: - 32.8, 95% CI: - 44.34, - 21.28), and sperm motility decreased by 37% (WMD: - 0.37, 95% CI: - 0.47, - 0.27). Sperm counts decreased slightly (WMD: - 3.03, 95% CI: - 3.42, - 2.64) in an intratesticular injection of low-dose busulfan (4 - 6 mg/kg), and the model almost returned to normal after one seminiferous cycle. CONCLUSION: The model using low-dose busulfan (10 - 20 mg/kg) returned to normal after 10 - 15 weeks. However, in some spermatogenesis cycles, testicular weight reduction and testicular spermatogenic function damage were not proportional to busulfan dose. Sperm counts and motility results in different studies had significant heterogeneity. Standard protocols for sperm assessment in animal models were needed to reduce heterogeneity between studies.

Pancreatic injury is associated with poor prognosis in severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. Previous studies have mainly focused on the epidemiological and clinical characteristics of patients with SFTS, while pancreatic injury has received little attention. The purpose of this study is to investigate the effect of pancreatic injury on the prognosis of patients with SFTS. A total of 156 SFTS patients were included in the analysis from April 2016 to April 2022. Multivariable logistic regression analysis showed that pancreatic injury (OR=3.754, 95% CI 1.361-79.036, P=0.024) and neurological symptoms (OR=18.648, 95% CI 4.921-70.668, P<0.001) were independent risk factors for patient death. The receiver operating characteristic (ROC) curve indicated that serum pancreatic enzymes (PEs) were predictive of progression to death in SFTS patients. The area under the curve (AUC) for amylase (AMY) was 0.711, with an optimal cut-off value of 95.5 (U/L), sensitivity of 96.4%, and specificity of 35.9%. Lipase (LIP) had an AUC of 0.754, an optimal cut-off value of 354.75 (U/L), a sensitivity of 75%, and a specificity of 67.2%. Thus, pancreatic injury is associated with a poor prognosis of SFTS and can be used as an important reference for SFTS disease determination and prognostic assessment.