IgG4-related disease （IgG4-RD） is an idiopathic fibroinflammatory condition characterized by a predilection for tumor-forming lesions， an increase in the serum level of IgG4， excessive infiltration of IgG4-positive plasma cells， storiform fibrosis， and/or obliterative phlebitis. This article reports a rare case of IgG4-RD in which the patient developed recurrent transient ischemic attacks （TIA） after the diagnosis of IgG4-RD. This report explores the potential pathological mechanisms， clinical features， treatment， and prognosis of IgG4-RD with TIA， in order to enhance the awareness of the possible neurological complications associated with IgG4-R among clinicians.
Glucocorticoids

Objective To investigate the fluctuations in the population density of Aedes albopictus and changes in the population density of Ae. albopictus in different geographical areas and different breeding habitats in Guangdong Province from 2018 to 2023, so as to provide insights into prevention and control of mosquito-borne infectious diseases in the province. Methods Ae. albopictus surveillance sites were assigned in 1 609 townships (streets) from 121 districts (counties) of 21 cities in Guangdong Province during the period between March and November from 2018 to 2023. The surveillance of the population density of Ae. albopictus was performed once a month in each surveillance site, and once a month in specific settings in cities where dengue were highly prevalent in Guangdong Province from December to February of the next year during the period from 2018 through 2023. Four streets (villages) were selected in each surveillance site according to the geographic orientation, and mosquito ovitraps were assigned in gardens, rooftops or public green belts at residential areas, parks, hospitals and construction sites. All mosquito ovitraps were collected, and the mosquito ovitrap index (MOI) was calculated. The population density of Ae. albopictus was classified into four grades in each surveillance site according to MOI, including no risk, low risk, medium risk and high risk. The risk classification of the Ae. albopictus density was analyzed in each surveillance site each year from 2018 to 2023, and the population density of Ae. albopictus was analyzed at different months and in different geographical areas and breeding habitats. Results A total of 118 241 Ae. albopictus surveillance sites were assigned in 21 cities of Guangdong Province from 2018 to 2023, and there were 68.26% of the surveillance sites with the population density of Ae. albopictus that met the requirements for dengue prevention and control, among which low, medium and high risk surveillance sites accounted for 23.61%, 6.67% and 1.47%. The risk classification of the Ae. albopictus density increased rapidly in Guangdong Province since April to May each year from 2018 to 2023, and then gradually reduced since September to October, with the peak during the period between May and July. The mean MOI was 4.21 at each surveillance site in Guangdong Province during the period from 2018 to 2023, with 4.69, 4.80, 4.38, 3.82, 3.38, and 4.33 from 2018 to 2023, respectively. The MOI was 4.35, 4.43, 3.53 and 3.58 in the Pearl River Delta region, and eastern, western, and northern Guangdong Province, respectively, and was 4.18, 5.44, 4.75, 3.24, 4.27 and 3.70 in residential areas, parks, construction sites, hospitals, waste collection stations, and other breeding habitats, respectively. Conclusions The population density of adult Ae. albopictus peaked in Guangdong Province during the period between May and July from 2018 to 2023, with a high density of Ae. albopictus in the Pearl River Delta region and eastern Guangdong Province. Targeted Ae. albopictus control measures are recommended to be implemented prior to the peak of the Ae. albopictus population density to reduce the development of mosquito-borne infectious diseases.

Objective:To investigate the impact of BMI1 expression in OSCC on the recruitment and differentiation of tumor-associat-ed macrophages(TAMs).Methods:BMI1 expression in 519 cases of OSCC tissues and 44 normal controls was analyzed using online datasets of GEPIA 2.0,and validated in 3 cases of OSCC samples and controls by qRT-PCR and western blotting.The function of BMI1/NF-κB axis during OSCC carcinogenesis was investigated by CCK8 assays,wound healing test and transwell assays.Macrophage phenotypes and recruitment were determined using qRT-PCR and western blotting following coculture of the cells with human monocyte cells(THP-1)by OSCC conditioned medium.Moreover,a cell line-derived xenograft(CDX)model was used to detect the effect of BMI1 on tumor growth in vivo.Results:Compared with the normal tissues and cells,the expression level of BMI1 in OSCC tissues and cells was significantly upregulated.BMI1 knockdown impaired the proliferation,migration,and invasion abilities of OSCC cell lines in NF-κB-dependent manner.Furthermore,OSCC cells with high BMI1 expression inhibited the migration of THP-1 cells,promoted M2-like macrophage polarization through NF-κB pathway in vitro.Xenograft experiments further confirmed the inhibitory effect of BMI1 knockdown on the tumorigenesis ability of OSCC cells in vivo.Conclusion:BMI1 promotes M2-like polarization by regulating NF-κB and may be used as a potential therapeutic target for antitumor immunity.

ObjectiveTo investigate the effect of circSLC8A1_005 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe effect of adenovirus-mediated overexpression of circSLC8A1_005 on the expression of fibrosis-related genes， collagen type I alpha 1 chain （Col1a1）， collagen type Ⅲ alpha 1 chain （Col3a1） and smooth muscle actin alpha 2 （Acta2）， in mouse cardiac fibroblasts （mCFs） were detected. The proliferation and migration activities of mCFs were detected by EdU and wound-healing assay， respectively. Dual luciferase reporter gene assay was performed to detect the activity of potential internal ribozyme entry site （IRES） in circSLC8A1_005. CircSLC8A1_005-translated protein， SLC8A1-605aa， and its intracellular distribution was identified by Western blot assay. The effect of SLC8A1-605aa protein on transcription activity of Sod2 gene was detected by the dual luciferase reporter gene assay. RNA binding protein immunoprecipitation （RIP） was utilized to verify the interaction between SLC8A1-605aa and superoxide dismutase 2 （Sod2） mRNA. Actinomycin D treatment was used to detect the effect of SLC8A1-605aa on Sod2 mRNA stability in mCFs. ResultsAn efficient adenovirus-mediated overexpression of circSLC8A1_005 was achieved in mCFs. The enforced expression of circSLC8A1_005 suppressed proliferation and migration of mCFs， and inhibited the expression of fibrosis-related genes in mCFs. The dual luciferase reporter gene assay revealed the activities of 2 IRES in circSLC8A1_005. Results of Western blot assay showed that circSLC8A1_005 could translate protein SLC8A1-605aa with the prospected molecular weight of 70 ku， which is predominantly distributed in the nucleus. Overexpression of the circSLC8A1_005 and SLC8A1-605aa could consistently inhibit the fibrotic phenotype of mCFs. SLC8A1-605aa could up-regulate superoxide dismutase 2 （Sod2） expression， but not at the transcriptional level. RIP assay indicated that SLC8A1-605aa could specifically interact with Sod2 mRNA， and the results of actinomycin D assay showed that SLC8A1-605aa could enhance the stability of Sod2 mRNA in mCFs. ConclusionCircSLC8A1_005 inhibits the fibrotic phenotype of cardiac fibroblasts via translating SLC8A1-605aa protein， and SLC8A1-605aa may be a potential target for the treatment of myocardial fibrosis.

Objective:To investigate the impact of body mass index (BMI) on the postoperative complications of open pancreaticoduodenectomy (OPD).Methods:The preoperative, operative and postoperative data of 234 patients who underwent OPD in the Department of the Hepatobiliary and Pancreatic Surgery of First Affiliated Hospital affiliated to Naval Medical University from January 2015 to June 2016 were analyzed retrospectively. According to the Asian BMI standard, the patients were divided into three groups: underweight group (BMI<18.5 kg/m 2, n=32), normal weight group (18.5 kg/m 2≤BMI<23.0 kg/m 2, n=110) and overweight group (BMI≥23.0 kg/m 2, n=92). Normal weight group was compared with underweight group and overweight group, respectively, to analyze the relationship between BMI and intraoperative parameters and major postoperative complications of OPD. Results:The incidence of diabetes in underweight group was lower than that in normal weight group, and the proportion of ASA score 3 in underweight group was higher than that in normal weight group, and there were significantly statistical differences (both P value <0.05). There was no significant difference on the other variables between underweight group, normal weight group and overweight group. The operation time, intraoperative hemorrhage volume >800 ml and intraoperative blood transfusion rate were not statistically different between underweight group and normal weight group, but overweight group had obviously higher intraoperative blood transfusion rate than normal weight group and the difference was statistically significant ( P<0.05). Underweight group had more postoperative intraperitoneal hemorrhage and postoperative blood transfusion rate than normal weight group, and the readmission rate in underweight group was less than that in normal weight group; the incidence of clinically related-post operative pancreatic fistula, postoperative infection, gastrointestinal bleeding and delayed gastric emptying in overweight group were significantly higher than those in normal weight group, and there were significantly statistical differences (all P value <0.05). In underweight group, normal weight group and overweight group, the average length of hospital stay were 9.9 days, 11.3 days, 15 days, and the total hospitalization expenses were 63663.04 yuan, 66241.78 yuan and 80484.31 yuan, respectively. Conclusions:Compared to normal weight patients, the difficulty of OPD in underweight patients does not increase, while the difficulty of OPD in overweight patients increases. Underweight and overweight could both increase the postoperative complications of OPD to some extent.

Abstract: Objective　To study severe fever with thrombocytopenia syndrome virus (SFTSV) in tick samples from different species and genera in Suizhou City, Hubei Province, China, and to explore the phylogenetic relationship between ticks and patients sources of viruses at the molecular evolutionary level. Methods In 2016 and 2017, over a continuous two-year period, 1 158 ticks were collected from Suizhou, Hubei, and their species and genera were identified. Meanwhile, 86 serum samples were collected to detect SFTSV RNA by real-time quantitative reverse transcription-PCR. All viral RNA-positive supernatants of tick homogenates were inoculated into Vero cells for viral isolation, and full genome sequencing of isolated strains was conducted. Phylogenetic tree research on SFTSV strains from ticks and cases was performed using the bootstrapped maximum-likelihood (1 000 iterations) method with Molecular Evolutionary Genetics Analysis (MEGA) software, ver. 11.0 to provide confidence estimates. Results Haemaphysalis longicornis, Ixodes sinensis, and Rhipicephalus microplus were the dominant species (95.34%) in Suizhou City, Hubei Province, China. Tick samples were pooled according to their species and developmental stage, yielding 832 pools, of which 4 were positive for SFTSV by qRT-PCR. The overall minimum infection rate (MIR) in the region was 0.35%. One SFTSV strain named HB 2016-P35, was successfully isolated from Haemaphysalis longicornis and demonstrated high homology to 16 previously reported patient-derived viruses in Hubei Province, especially to the human strain HB 2017-49 from the same region, with a genome similarity of 99.9%. In addition, the molecular phylogenetic analysis revealed five distinct SFTSV genotypes in Hubei, covering almost all currently known SFTSV genotypes. Conclusions Some areas of Suizhou City, Hubei Province, demonstrate a relatively low level of SFTSV carrying and transmission by ticks. The new SFTSV strain isolated from ticks exhibits similar genotype characteristics and high sequence homology with viruses carried by cases in surrounding cases. The study suggests that tick-to-human transmission is most likely the pathway for human infection with SFTSV, highlighting the need for continual and long-term monitoring of tick carriage of SFTSV in endemic areas.

Natural compounds demonstrate unique therapeutic advantages for cancer treatment, primarily through direct tumor suppression or interference with the tumor microenvironment (TME). Glycyrrhizic acid (GL), a bioactive ingredient derived from the medicinal herb Glycyrrhiza uralensis Fisch., and its sapogenin glycyrrhetinic acid (GA), have been recognized for their ability to inhibit angiogenesis and remodel the TME. Consequently, the combination of GL with other therapeutic agents offers superior therapeutic benefits. Given GL's amphiphilic structure, self-assembly capability, and liver cancer targeting capacity, various GL-based nanoscale drug delivery systems have been developed. These GL-based nanosystems exhibit angiogenesis suppression and TME regulation properties, synergistically enhancing anti-cancer effects. This review summarizes recent advances in GL-based nanosystems, including polymer-drug micelles, drug-drug assembly nanoparticles (NPs), liposomes, and nanogels, for cancer treatment and tumor postoperative care, providing new insights into the anti-cancer potential of natural compounds. Additionally, the review discusses existing challenges and future perspectives for translating GL-based nanosystems from bench to bedside.
Animals ; Humans ; Antineoplastic Agents/therapeutic use* ; Glycyrrhizic Acid/therapeutic use* ; Liposomes/chemistry* ; Micelles ; Nanoparticles/chemistry* ; Neoplasms/pathology* ; Tumor Microenvironment/drug effects* ; Nanoparticle Drug Delivery System/therapeutic use*

Natural plant-derived diterpenoids are a class of compounds with diverse structures and functions. These compounds are widely used in pharmaceuticals, cosmetics and food additives industries because of their pharmacological properties such as anticancer, anti-inflammatory and antibacterial activities. In recent years, with the gradual discovery of functional genes in the biosynthetic pathway of plant-derived diterpenoids and the development of synthetic biotechnology, great efforts have been made to construct a variety of diterpenoid microbial cell factories through metabolic engineering and synthetic biology, resulting in gram-level production of many compounds. This article summarizes the construction of plant-derived diterpenoid microbial cell factories through synthetic biotechnology, followed by introducing the metabolic engineering strategies applied to improve plant-derived diterpenoids production, with the aim to provide a reference for the construction of high-yield plant-derived diterpenoid microbial cell factories and the industrial production of diterpenoids.
Diterpenes/metabolism* ; Biotechnology ; Metabolic Engineering ; Biosynthetic Pathways/genetics* ; Plants/genetics* ; Synthetic Biology

OBJECTIVE: To explore the genetic etiology for a child with profound intellectual disabilities and obvious behavioral abnormalities. METHODS: A male child who had presented at the Zhongnan Hospital of Wuhan University on December 2, 2020 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Short tandem repeat (STR) analysis was carried out to determine its parental origin. The splicing variant was also validated in vitro with a minigene assay. RESULTS: WES results revealed that the child had harbored a novel splicing variant of c.176-2A>G in the PAK3 gene, which was inherited from his mother. The results of minigene assay have confirmed aberrant splicing of exon 2. According to the guidelines from the American College of Medical Genetics and Genomics, it was classified as a pathogenic variant (PVS1+PM2_Supporting+PP3). CONCLUSION The novel splicing variant c.176-2A>G of the PAK3 gene probably underlay the disorder in this child. Above finding has expanded the variation spectrum of the PAK3 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.
Child ; Female ; Humans ; Male ; Pregnancy ; Exons ; Intellectual Disability/genetics* ; Mothers ; Mutation ; p21-Activated Kinases/genetics* ; Parents ; RNA Splicing

OBJECTIVE: To investigate the mechanism of regulatory T cells (Treg) in heat stroke (HS)-induced acute kidney injury (AKI). METHODS: Male SPF Balb/c mice were randomly divided into control group, HS group (HS+Rat IgG), HS+PC61 group, and HS+Treg group (n = 6). The HS mice model was established by making the body temperature of the mice reach 42.7 centigrade at room temperature 39.5 centigrade with relative humidity 60% for 1 hour. In HS+PC61 group, 100 μg PC61 antibody (anti-CD25) was injected through the tail vein in consecutive 2 days before the model was established to eliminate Tregs. Mice in HS+Treg group was injected with 1×10⁶ Treg via tail vein immediately after successful modeling. The proportion of Treg infiltrated in the kidney, serum creatinine (SCr) and histopathology, levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) both in the serum and kidney tissue, as well as proportion of neutrophils and macrophages located in the kidney were observed at 24 hours after HS. RESULTS: HS dampened renal function and exaggerated kidney injury, up-regulated levels of inflammatory cytokines both in local kidney and circulation, and increased infiltration of neutrophils and macrophages to the injured kidneys. The proportion of Treg (Treg/CD4⁺) infiltrated in kidney was significantly decreased in HS group, compared with control group [(3.40±0.46)% vs. (7.67±0.82)%, P < 0.01]. Compared with HS group, local Tregs in kidney were almost completely depleted via PC61 antibody [(0.77±0.12)% vs. (3.40±0.46)%, P < 0.01]. Depletion of Tregs could exacerbate HS-AKI, indicating by increased serum creatinine [SCr (mmol/L): 348.22±35.36 vs. 254.42±27.40, P < 0.01] and pathological injury (Paller score: 4.70±0.20 vs. 3.60±0.20, P < 0.01), incremental levels of IFN-γand TNF-α both in injured kidney and serum [serum IFN-γ (ng/L): 747.70±64.52 vs. 508.46±44.79, serum TNF-α (ng/L): 647.41±26.62 vs. 464.53±41.80, both P < 0.01], and more infiltrated neutrophils and macrophages in the injured kidney [neutrophil proportion: (6.63±0.67)% vs. (4.37±0.43)%, macrophage proportion: (38.70±1.66)% vs. (33.19±1.55)%, both P < 0.01]. On the contrast, adoptive transfer of Tregs could reverse the aforementioned effects of Treg depletion, indicating by incremental proportion of Tregs in the injured kidney [(10.58±1.19)% vs. (3.40±0.46)%, P < 0.01], decreased serum creatinine [SCr (mmol/L): 168.24±40.56 vs. 254.42±27.40, P < 0.01] and pathological injury (Paller score: 2.73±0.11 vs. 3.60±0.20, P < 0.01), reduced levels of IFN-γ and TNF-α both in injured kidney and serum [serum IFN-γ (ng/L): 262.62±22.68 vs. 508.46±44.79, serum TNF-α (ng/L): 206.41±22.58 vs. 464.53±41.80, both P < 0.01], and less infiltrated neutrophils and macrophages in the injured kidney [neutrophil proportion: (3.04±0.33)% vs. (4.37±0.43)%, macrophage proportion: (25.68±1.93)% vs. (33.19±1.55)%, both P < 0.01]. CONCLUSIONS Treg might be involved in HS-AKI, possibly via down-regulation of pro-inflammatory cytokines and infiltration of inflammatory cells.
Male ; Animals ; Mice ; Rats ; T-Lymphocytes, Regulatory ; Creatinine ; Tumor Necrosis Factor-alpha ; Heat Stroke ; Acute Kidney Injury ; Cytokines ; Interferon-gamma