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

Ganjiang (Zingiberis Rhizoma, ZR) and Jiangtan (Carbonized Zingiberis Rhizoma, CZR) have long been used in traditional Chinese medicine (TCM) with a rich history in the treatment of various ailments. While ZR and CZR obviously stem from the same botanical source, their attributes, chemical compositions, pharmacological behaviors, and clinical applications are different owing to variations in the extent of drying and processing they undergo. In this paper, data pertaining to ZR and CZR were retrieved from databases including China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, and Google Scholar. These sources were scrutinized to elucidate the distinctions between ZR and CZR arising from carbonization processing in terms of their ethnopharmacology, quality control, chemical compositions, biological activities, pharmacological mechanisms, and clinical uses. In this study, a total of 56 chemical constituents were identified and isolated from ZR and CZR, which primarily encompassed volatile oils, gingerols, and diphenylheptane compounds. CZR's pharmacological effects include hemostatic, anti-oxidant, analgesic, antibacterial, anti-cancer, and other biological activities. ZR has pungent and warm properties. It is a Yang-supplementing herbal medicine for ailments exacerbated by cold or damp climatic influences. CZR is a product of ZR after undergoing high temperature, with diminished intensity of its pungent and warm attributes. This change leads to a more gradual treatment efficacy, renowned hemostatic effects and its ability to gently invigorate the spleen and effectively alleviate diarrhea. Currently, research on the pharmacological mechanism of CZR is mainly focused on the effects of CZR on coagulation and fibrinolysis. Although the healing effect of CZR has long been known, and some correlation has been found between the changing composition and the changing color of the decoctions, people still lack relatively clear processing mechanisms to reflect the characteristics and specific quality standards of the ingredients of CZR's hemostatic effect. This review provides a systematic summary on quality control, chemical composition, ethnopharmacology, and pharmacology of CZR, offering novel perspectives for advancing the exploration of additional carbonized herbal medicine and fostering their application in clinical settings

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.

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*

Non-valvular atrial fibrillation is a common arrhythmia and a major risk factor for cardioembolic stroke. Small cerebral vascular disease is a syndrome of clinical, cognitive, imaging, and pathological manifestations caused by intracranial small vascular lesions. The imaging findings on cranial magnetic resonance usually shows recent subcortical small infarction, vascularised lacunae, white matter hypersignal, perivascular space enlargement, cerebral microhemorrhage, and brain atrophy. It is a major cause of neurological loss and cognitive function decline in the elderly. Current studies suggest that atrial fibrillation may increase the imaging load of cerebral small vessel disease through a series of mechanisms such as microembolization, hypoperfusion, inflammation, endothelial dysfunction, and lymphoid system dysfunction. The imaging of cerebral small vessel disease with atrial fibrillation has a potential relationship with cognitive function decline and is related to the occurrence and prognosis of stroke, even more has a potential role in suggesting the etiology and secondary prevention strategies of ischemic stroke.
Aged ; Atrial Fibrillation/epidemiology* ; Cerebral Small Vessel Diseases/complications* ; Cognitive Dysfunction/etiology* ; Humans ; Magnetic Resonance Imaging ; Stroke/etiology*

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.

With the emergence of drug resistance in Western medicine, the repeated administration of clinical first-line drugs becomes more severe. There are many factors leading to multidrug resistance(MDR), so it is very difficult to solve the problem. Since traditional Chinese medicine(TCM) has been used in the field of MDR in recent years, the research on the transporter-associated drug resistance and intervention of TCM has gradually become a hot spot. Therefore, in order to further explore the relationships among drug resistance, transporters, and TCM intervention, we review the relevant research progress in recent years and comb the achievements and limitations of this research at present. In the end, we put forward the research direction of changing body's ADME through the host's transporters and gastrointestinal flora, which provides new ideas for future research.
Drug Resistance, Multiple ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Membrane Transport Proteins/genetics*

Triptolide (TP), an active component of Tripterygium wilfordiiHook. f. (TWHF), has been widely used for centuries as a traditional Chinese medicine. However, the clinical application of TP has been restricted due to multitarget toxicity, such as hepatotoxicity. In this study, 28 days of oral TP administration (100, 200, or 400 μg·kg