Objective: To investigate the effects of Erianin on cell proliferation and apoptosis in human oral squamous cell carcinoma (OSCC) cells, providing a research foundation for the clinical treatment of OSCC. Methods: Erianin was applied to OSCC cells (CAL27 and SCC9) at concentrations of 0, 2.5, 5, and 10 μmol/L. The inhibitory effect of Erianin on OSCC cell proliferation was evaluated using CCK-8 and soft agar colony formation assays. Western blotting (WB) was employed to analyze the expression levels of anti-apoptotic proteins B-cell lymphoma-extra large (Bcl-xL), B-cell lymphoma-2 (Bcl-2), myeloid cell leukemia-1 (Mcl-1), and apoptotic protein cleaved-Caspase 3 (c-Caspase 3) in OSCC cells. Caspase 3 activity was further assessed using a caspase 3 activity detection kit to examine the pro-apoptotic effect of Erianin in OSCC cells. Mcl-1 overexpression was induced in CAL27 cells via plasmid transfection, and the influence of Mcl-1 on the effects of Erianin in CAL27 cells was analyzed by WB and caspase 3 activity measurement. All animal experiments were approved by the Ethics Committee of Hunan Cancer Hospital. A CAL27 xenograft mouse model was established and randomly divided into two groups (n = 5): the treatment group received intraperitoneal injection of Erianin (25 mg/kg), while the control group was injected with phosphate-buffered saline (PBS) as the vehicle. Immunohistochemistry (IHC) was used to detect the expression levels of Ki67 and Mcl-1 in the tumor tissues. Results: Erianin inhibited the proliferation of CAL27 and SCC9 cells in a dose-dependent manner and downregulated the protein expression of Mcl-1, with minimal effects on Bcl-2 and Bcl-xL. Furthermore, Erianin induced apoptosis in OSCC cells, as evidenced by increased expression of c-Caspase 3 and enhanced caspase 3 activity (P<0.001). Overexpression of Mcl-1 inhibited the Erianin-induced increase in c-Caspase 3 protein levels and caspase 3 activity. In vivo results were consistent with the in vitro findings. After Erianin treatment, CAL27 cell growth in nude mice was suppressed (P<0.001), and the expression levels of the proliferation marker Ki67 and the anti-apoptotic protein Mcl-1 in the tumor tissues were downregulated (P<0.001). Conclusion Erianin exhibits potent anti-tumor effects, effectively inhibiting the proliferation of OSCC cells and inducing apoptosis. The underlying mechanism may involve the downregulation of the pro-survival protein Mcl-1.

Acute cerebral infarction predominantly occurs in middle-aged and elderly individuals with multiple underlying diseases， and it is often accompanied by atherosclerosis or heart diseases. It has a low incidence rate in children and adolescents， who tend to have atypical symptoms in the early stage， leading to misdiagnosis or missed diagnosis. With the continuous development of imaging technology， the diagnosis of cerebral infarction has become more precise， which helps to further clarify the etiology of cerebral infarction and identify an increasing number of patients with different subtypes of cerebral infarction in clinical practice. This article reports a rare case of a pediatric patient with acute cerebral infarction caused by primary central nervous system vasculitis， which led to neurological dysfunction， in order to improve the awareness of cerebral infarction in children among clinicians.
Vasculitis

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

Objective:The three-dimensional(3D) reconstruction method of calf perforator vessel was explored to provide the basis for clinical safe and accurate harvesting of calf chain perforator flap.Methods:Gelatin-lead oxide is automatically perfused the femoral artery of 3 fresh adult lower limbs specimens. Data were collected after the CT scan of the full limb, 3D reconstruction of bones, arteries and their perforators was processed in Mimics Research 19.0 software. Dynamic display of vascular hierarchy and adjacent relationships by adjusting CT values. And show the anatomical region of each perforator artery in different colors, measure the feeding area of the single perforator using Scion Image software. The 3D printed calf bone and vascular model can be used for direct observation. The specimen anatomy was measured according to a perforator vessel parameter with an outer diameter of 0.5 mm through the deep fascia. The number of perforators, vessle pedicle length, and outer diameter were observed and statistically analyzed.Results:The digitized 3D reconstruction images can clearly show the 3D structured of the calf artery and perforator vessels and micro vessels, as well as the course, distribution characteristics of blood vessels, and the 3D relationship with adjacent structures. The printed 3D model visually observes the hierarchy of the perforator vessels and the anastomosis relationship between the perforators. 3 calf specimen arteries with perforator artery 22±4, vessel pedicle length (46.7±18.3) mm, outer diameter (0.8±0.3) mm, the average blood supply area of the single perforator (38.2±10.7) cm 2. Conclusion:The Mimics Research 19.0 software should be used to dynamically reconstruct the 3D structure of the branch vessel by adjusting the CT value, which improves the display effect of the perforator vessels. The 3D printing model makes the source, course, diameter and distribution range of the perforator vessels visually visible, which provides experimental support for the clinical construction of digital calf chain perforator flap harvest scheme for patients.

Objective:The three-dimensional(3D) reconstruction method of calf perforator vessel was explored to provide the basis for clinical safe and accurate harvesting of calf chain perforator flap.Methods:Gelatin-lead oxide is automatically perfused the femoral artery of 3 fresh adult lower limbs specimens. Data were collected after the CT scan of the full limb, 3D reconstruction of bones, arteries and their perforators was processed in Mimics Research 19.0 software. Dynamic display of vascular hierarchy and adjacent relationships by adjusting CT values. And show the anatomical region of each perforator artery in different colors, measure the feeding area of the single perforator using Scion Image software. The 3D printed calf bone and vascular model can be used for direct observation. The specimen anatomy was measured according to a perforator vessel parameter with an outer diameter of 0.5 mm through the deep fascia. The number of perforators, vessle pedicle length, and outer diameter were observed and statistically analyzed.Results:The digitized 3D reconstruction images can clearly show the 3D structured of the calf artery and perforator vessels and micro vessels, as well as the course, distribution characteristics of blood vessels, and the 3D relationship with adjacent structures. The printed 3D model visually observes the hierarchy of the perforator vessels and the anastomosis relationship between the perforators. 3 calf specimen arteries with perforator artery 22±4, vessel pedicle length (46.7±18.3) mm, outer diameter (0.8±0.3) mm, the average blood supply area of the single perforator (38.2±10.7) cm 2. Conclusion:The Mimics Research 19.0 software should be used to dynamically reconstruct the 3D structure of the branch vessel by adjusting the CT value, which improves the display effect of the perforator vessels. The 3D printing model makes the source, course, diameter and distribution range of the perforator vessels visually visible, which provides experimental support for the clinical construction of digital calf chain perforator flap harvest scheme for patients.

Objective To investigate ecological isolation between Oncomelania hupensis snail populations in hilly regions and marshland and lake regions in Yuanjiang valley, Changde City, Hunan Province, and to unravel its underlying mechanisms. Methods Taoyuan County, Shimen County, Linli County and Lixian County in Changde City were selected as snail sampling sites in hilly regions, and Lixian County, Jinshi City, West Lake Administration District, Hanshou County and Dingcheng District were selected as snail sampling sites in marshland and lake areas. Cytochrome C oxidase 1 (cox 1) gene was amplified in snail samples and sequenced. The genetic sequences of O. hupensis snails were aligned using the software MEGA 11, and the haplotypes of O. hupensis snails were determined using the software DNASP 5.10.01. The phylogenetic tree was generated using Bayesian inference with the software MrBayes 3.2, and analysis of molecular variance (AMOVA) was performed to analyze the source of genetic divergence and estimate the genetic divergence index (F_ST) among snail populations with the software Arlequin 3.5.2.2. The genetic barrier among 11 O. hupensis snail populations was estimated using the Monmonier algorithm of adegenet toolkit in R package. The settings with “land in winter and water in summer” in the Yuanjian River section were divided into two categories according to the upstream and downstream, and the areas with “land in winter and water in summer” in the upstream and downstream were transformed into raster data, and then loaded into the software Fragstats 4 for analysis of landscape indicators. The trends in changes of digital elevation were extracted from the Yuanjiang River section based on the digital elevation model, and made three-dimensional visualization using the R package. Results The mitochondrial cox 1 gene were amplified in 165 O. hupensis snais from 11 sampling sites and sequenced, and a total of 152 valid gene sequences were obtained, with 46 haplotypes or 9 populations determined. No haplotype was shared in snails between Taoyuan County and Dingcheng District and Hanshou County along the downstream of the Yuanjiang River. The total area of settings with “land in winter and water in summer” was 617.66 hm² in the upsteram of the Yuanjiang River, which consisted of 473 patches, with each patch measuring 1.31 hm², the largest area index of 0.735 2, the landscape division index of 0.999 9, and the landscape shape index of 45.293 7. The total area of settings with “land in winter and water in summer” was 9 956.92 hm² in the downstream of the Yuanjiang River, which consisted of 771 patches, with each patch measuring 12.91 hm², the largest area index of 97.839 9, the landscape division index of 0.042 7, and the landscape shape index of 7.249 6. The area of settings with “land in winter and water in summer” was much larger in the downstream than that in the upstream of the Yuanjiang River, and the stronger landscape connectivity and non-remarkable alteration of riverbed elevation provided suitable habitats for snail breeding. Conclusion The hydrological and environmental characteristics of the upstream of the Yuanjiang River restrain the breeding and spread of O. hupensis, resulting in ecological isolation between Oncomelania hupensis in Taoyuan County and those in the downstream of Yuanjiang River.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

OBJECTIVES: There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM. METHODS: The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0. RESULTS: Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%). CONCLUSIONS In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Humans ; Immunologic Factors/therapeutic use* ; Male ; Middle Aged ; Multiple Myeloma/therapy* ; Neoplasm Staging ; Pain ; Prognosis ; Proteasome Inhibitors/therapeutic use*

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine α-1,3-galactose epitopes (αGal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END⁺/Gal⁺-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-γ). CTLs targeted cells expressing αGal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.