A Biomimetic Multifunctional Nanoframework for Symptom Relief and Restorative Treatment of Acute Liver Failure.

Acute liver failure (ALF) is a rare and serious condition characterized by major hepatocyte death and liver dysfunction. Owing to the limited therapeutic options, this disease generally has a poor prognosis and a high mortality rate. When ALF cannot be reversed by medications, liver transplantation is often needed. However, transplant rejection and the shortage of donor organs still remain major challenges. Most recently, stem cell therapy has emerged as a promising alternative for the treatment of liver diseases. However, the limited cell delivery routes and poor stability of live cell products have greatly hindered the feasibility and therapeutic efficacy of stem cell therapy. Inspired by the functions of mesenchymal stem cells (MSCs) primarily through the secretion of several factors, we developed an MSC-inspired biomimetic multifunctional nanoframework (MBN) that encapsulates the growth-promoting factors secreted by MSCs via combination with hydrophilic or hydrophobic drugs. The red blood cell (RBC) membrane was coated with the MBN to enhance its immunological tolerance and prolong its circulation time in blood. Importantly, the MBN can respond to the oxidative microenvironment, where it accumulates and degrades to release the payload. In this work, two biomimetic nanoparticles, namely, rhein-encapsulated MBN (RMBN) and N-acetylcysteine (NAC)-encapsulated MBN (NMBN), were designed and synthesized. In lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced and acetaminophen (APAP)-induced ALF mouse models, RMBN and NMBN could effectively target liver lesions, relieve the acute symptoms of ALF, and promote liver cell regeneration by virtue of their strong antioxidative, anti-inflammatory, and regenerative activities. This study demonstrated the feasibility of the use of an MSC-inspired biomimetic nanoframework for treating ALF.

Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer.

Breast cancer is a common cancer in women worldwide. The existing clinical treatment strategies have been able to limit the progression of breast cancer and cancer metastasis, but abnormal metabolism, immunosuppression, and multidrug resistance involving multiple regulators remain the major challenges for the treatment of breast cancer. Adenosine 5'-monophosphate (AMP)-Activated Protein Kinase (AMPK) can regulate metabolic reprogramming and reverse the "Warburg effect" via multiple metabolic signaling pathways in breast cancer. Previous studies suggest that the activation of AMPK suppresses the growth and metastasis of breast cancer cells, as well as stimulating the responses of immune cells. However, some other reports claim that the development and poor prognosis of breast cancer are related to the overexpression and aberrant activation of AMPK. Thus, the role of AMPK in the progression of breast cancer is still controversial. In this review, we summarize the current understanding of AMPK, particularly the comprehensive bidirectional functions of AMPK in cancer progression; discuss the pharmacological activators of AMPK and some specific molecules, including the natural products (including berberine, curcumin, (-)-epigallocatechin-3-gallate, ginsenosides, and paclitaxel) that influence the efficacy of these activators in cancer therapy; and elaborate the role of AMPK as a potential therapeutic target for the treatment of breast cancer.

Environmental and meteorological factors on the risk of lipid-abnormal dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the impact of meteorological factors in different environments in the eastern and western regions of China on the incidence of lipid-abnormal dry eye.METHODS: This is a multicenter retrospective study. From March 1, 2021 to February 28, 2022, all patients with dry eye were selected from the ophthalmology clinic of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine and Friendship Hospital of Xinjiang Yili Kazakh Autonomous Prefecture. General data(gender, age, employment and education)and climate data for outdoor environments(temperature, humidity, air quality index and wind)on the day of the visit were collected. Patients who met the inclusion and exclusion criteria were selected. Single factor, multiple factors and nonlinear model analysis were applied to identify environmental factors of lipid-abnormal dry eye in both regions.RESULTS: There was no significant difference in the incidence of lipid-abnormal dry eye between Nanjing and Yili in different seasons. The incidence of lipid-abnormal dry eye in Yili was significantly higher in all seasons than in Nanjing(P<0.001). The results of univariate research showed that the factors affecting the incidence of lipid-abnormal dry eye were gender, employment, humidity, air quality, and wind. The results of multivariate Logistic regression analysis showed that humidity, temperature and air quality were statistically significant, and remained significant after adjusting for the three confounding factors of age, gender and employment situation. Nonlinear analysis showed that the probability of lipid-abnormal dry eye increased with the decrease of temperature when the temperature was below 10℃; within the range of 10℃～15℃, the probability of lipid-abnormal dry eye tended to stabilize. When the temperature exceeded 15℃, the probability of lipid-abnormal dry eye increased with the increase of temperature. Humidity was negatively correlated with the onset of lipid-abnormal dry eye. As humidity increased, the probability of lipid-abnormal dry eye decreased.CONCLUSIONS: The risk of lipid-abnormal dry eye in Yili is higher than that in Nanjing throughout the four seasons. Humidity, temperature, air quality and other environmental and meteorological factors can all affect the incidence of lipid-abnormal dry eye.

Analysis of emergency reconstruction of forearm Gustilo III B and III C fracture with complex tissue defect: outcomes and related factors / 中华显微外科杂志

Objective:To discuss outcomes of emergency repairing for Gustilo III B and III C fractures of forearm with complicated tissue defects and the related influence factors.Methods:From January 2014 to Feburary 2022, data of 98 cases of Gustilo III B and III C fractures with large compound defects of soft tissue, blood vessel, bone, tendon or muscle from elbow to wrist were collected. Primary debridement, bone fixation, wound coverage by free flap, bone transfer(or bone cement filling) or dynamic reconstruction of muscle were completed with emergency surgery in Department of Hand and Foot Microsurgery, Xi'an Fengcheng Hospital. Postoperative follow-ups were conducted through outpatient clinic visits, telephone and WeChat reviews. Video clips, questionnaires and the latest information of patients were also analysed. Rank sum test and Chi-square test were used to examine the relationship between independent variables such as general condition, disease condition and surgical procedures of chimeric tissue transfer group and simple flap transfer group, together with dependent variables such as limb salvage, number of surgery, wound healing, function scores, and complications. P<0.05 were further included in the regression equation to discover the relationship between multiple independent variables and dependent variables. Results:Follow-up lasted for 6-96 months, with an average of 71.1 months. In the chimeric group, the limb salvage rate was at 95.1%, with an infection rate of 8.50% and an average number of surgery was 2.13±0.89. In the simple flap transfer group, the limb salvage rate was at 87.5%, with an infection rate of 15.38% and an average number of surgery was 2.62±0.64. The good rate of Anderson score was 65.3% and the average score of Disability of the Arm, Shoulder and Hand(DASH) was 32.9(0-60) points for all the patients. There were significant differences in dependent variables of limb salvage and infection rate between the 2 groups ( P<0.05). Ischemia time and method of bone fixation led to significant differences in number of surgery ( P<0.05). Methods of bone fixation and the types of flap made significant differences in wound healing ( P<0.05). Underlying disease, bonedefect, Gustilo classification and method of bone fixation all contributed to the significant differences in function score ( P<0.05 or P<0.01) . Conclusion:Emergency surgery for repair of serious injury of forearm has a relatively high limb salvage rate and good functional effects. The limb salvage rate is not correlated with independent variables such as severity of injury, Mangledextremity Severity Score (MESS) and ischemia time, while transfer of a simple flap or a chimeric flap is significantly correlated with the limb salvage rate, infection and wound healing. The severity of injury, ischemia time and bone defect are correlated with functional assessment, number of surgery and bone healing.

Functional muscular transfer of lateral femoral muscle superficial region in emergency reconstruction of traumatic defects of dynamical muscle: A report of preliminary clinical study / 中华显微外科杂志

Objective:To explore the feasibility and clinical effect of emergency lateral thigh muscle transfer in functional reconstruction of major traumatic muscle defects.Methods:Emergency surgeries for 8 patients(7 males and 1 female) with muscle defects were carried out subject to emergently reconstruct the power of lateral femoral muscle superficial region, between March 2020 and December 2021, in the Department of Hand and Foot Microsurgery Hospital, Xi'an Fengcheng Hospital. The 8 patients were 23 to 52 years old with an average of 37.6 years old. Five patients injured by machine crush, 2 by heavy object crush and 1 by traffic accident. Five patients were in Gustilo III B injury in forearm, including 2 with flexor muscle group defects, 2 with extensor muscle group defects and 1 with defect of dorsal metacarpal flexor muscle and extensor muscle. Among the 5 patients, 2 patients had the defects in left forearm and 3 in right forearm. One patient had defect of right 1st metacarpal bone and skin and thenar muscle. One patient suffered a complete right upper arm detachment with musculocutaneous nerve being drawn out from the bicipital muscle. One patient had Gustilo III C injury in the right calf with defects of extensor hallucis longus and extensor digitorum. The areas of soft tissue defect were 10.0 cm×8.0 cm-36.0 cm×11.0 cm and the size of flaps was 12.0 cm×6.0 cm-38.0 cm×12.0 cm with the volumes of excised muscle at 18.0 cm×9.0 cm×1.5 cm-10.0 cm×2.0 cm×1.0 cm. The anatomical cross-section and length of the corresponding muscle on the healthy side were measured by musculoskeletal ultrasound. The chimeric tissue flap was designed on the anterolateral side of the thigh. The flap was designed according to the size of the wound and the corresponding flap. Then 1 or 2 muscle tissue blocks were designed and cut from the superficial region of the lateral femoral muscle according to the condition of the muscle defect, to cover the wound and reconstruct the muscle power. Postoperative follow-ups were conducted by scheduled hospital visit. The contents of follow-up included dynamic observation, evaluation and record through musculoskeletal ultrasound, electromyography and strength of muscle.Results:For the 8 patients who were subject to a muscle reconstruction, the transferred muscles and flaps survived in stage-one without vascular event. Postoperative follow-ups lasted for 10 to 32 months with an average of 19.6 months. The strength of muscle was evaluated according to the M 4 strength of muscle. Strength of muscle restored to M 4 or above in 7 patients who could lift, hook or push a heavy object in 5-30 kg of weight, with free joint movement. One patient restored the strength of muscle to M 3+. Muscle contraction was detected 2-4 months after surgery by musculoskeletal B ultrasound. The average ratio of contraction to resting cross sectional area in 5 cases was 1.45±0.42. The shape of limb was bilaterally symmetrical. There was no discomfort in the donor site and knee joint. The flaps were soft and glossy, with protective sensation restored. Conclusion:Muscle transfer from the lateral femoral muscle superficial region in emergency surgery for functional reconstruction of traumatic muscle defects is feasible and effective with a good clinical effect.

Analysis of Chinese Medical Syndrome Features of Ischemic Stroke Based on Similarity of Symptoms Subgroup / 中国结合医学杂志

OBJECTIVE@#To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients.@*METHODS@#By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup.@*RESULTS@#Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens.@*CONCLUSIONS@#There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.

Genetic and Phenotypic Variation of Campylobacter jejuni NCTC11168 Caused by flhA Mutation during Laboratory Passage / 生物医学与环境科学（英文）

OBJECTIVE@#Campylobacter jejuni NCTC11168 is commonly used as a standard strain for flagellar biosynthesis research. In this report, two distinguished phenotypic isolates (CJ1Z, flhA mutant strain, lawn; CJ2S, flhA complemented strain, normal colony) appeared during laboratory passages for NCTC11168.@*METHODS@#Phenotypic assessments, including motility plates, transmission electron microscopy, biofilm formation assay, autoagglutination assay, and genome re-sequencing for these two isolates (CJ1Z, flhA mutant strain; CJ2S, flhA complemented strain) were carried out in this study.@*RESULTS@#Transmission electron microscopy revealed that the flagellum was lost in CJ1Z. Phenotypic assessments and genome sequencing of the two isolates were performed in this study. The capacity for biofilm formation, colony auto-agglutination, and isolate motility was reduced in the mutant CJ1Z. Comparative genomic analysis indicated a unique native nucleotide insertion in flhA (nt, 2154) that caused the I719Y and I720Y mutations and early truncation in flhA.@*CONCLUSION@#FlhA has been found to influence the expression of flagella in C. jejuni. To the best of our knowledge, this is the first study to describe the function of the C-terminal of this protein.

Complete chloroplast genome sequencing and phylogeny of wild Atractylodes lancea from Yuexi, Anhui province / 中国中药杂志

This study investigated the choroplast genome sequence of wild Atractylodes lancea from Yuexi in Anhui province by high-throughput sequencing, followed by characterization of the genome structure, which laid a foundation for the species identification, analysis of genetic diversity, and resource conservation of A. lancea. To be specific, the total genomic DNA was extracted from the leaves of A. lancea with the improved CTAB method. The chloroplast genome of A. lancea was sequenced by the high-throughput sequencing technology, followed by assembling by metaSPAdes and annotation by CPGAVAS2. Bioiformatics methods were employed for the analysis of simple sequence repeats(SSRs), inverted repeat(IR) border, codon bias, and phylogeny. The results showed that the whole chloroplast genome of A. lancea was 153 178 bp, with an 84 226 bp large single copy(LSC) and a 18 658 bp small single copy(SSC) separated by a pair of IRs(25 147 bp). The genome had the GC content of 37.7% and 124 genes: 87 protein-coding genes, 8 rRNA genes, and 29 tRNA genes. It had 26 287 codons and encoded 20 amino acids. Phylogenetic analysis showed that Atractylodes species clustered into one clade and that A. lancea had close genetic relationship with A. koreana. This study established a method for sequencing the chloroplast genome of A. lancea and enriched the genetic resources of Compositae. The findings are expected to lay a foundation for species identification, analysis of genetic diversity, and resource conservation of A. lancea.

Evaluation of the efficacy and safety of Nocardia rubra cell wall skeleton immunotherapy for cervical high-risk HPV persistent infection / 中华妇产科杂志

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.

Population structure of food-borne Staphylococcus aureus in China / 中华流行病学杂志

Objective: To understand the population structure of food-borne Staphylococcus (S.) aureus in China. Methods: Whole genome sequencing was used to analyze 763 food-borne S. aureus strains from 16 provinces in China from 2006 to 2020. Multilocus sequence typing (MLST), staphylococcal protein A gene (spa) typing, and staphylococcal chromosome cassettemec (SCCmec) typing were conducted, and minimum spanning tree based on ST types (STs) was constructed by BioNumerics 7.5 software. Thirty-one S. aureus strains isolated from imported food products were also included in constructing the genome phylogenetic tree. Results: A total of 90 STs (20 novel types) and 160 spa types were detected in the 763 S. aureus isolates. The 72 STs (72/90, 80.0%) were related to 22 clone complexes. The predominant clone complexes were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, accounting for 82.44% (629/763) of the total. The STs and spa types in the predominant clone complexes changed over the years. The methicillin-resistant S. aureus (MRSA) detection rate was 7.60%, and 7 SCCmec types were identified. The ST59-t437-Ⅳa (17.24%, 10/58), ST239-t030-Ⅲ (12.07%, 7/58), ST59-t437-Ⅴb (8.62%, 5/58), ST338-t437-Ⅴb (6.90%, 4/58) and ST338-t441-Ⅴb (6.90%, 4/58) were the main types in MRSA strains. The genome phylogenetic tree had two clades, and the strains with the same CC, ST, and spa types clustered together. All CC7 methicillin sensitive S. aureus strains were included in Clade1, while 21 clone complexes and all MRSA strains were in Clade2. The MRSA strains clustered according to the SCCmec and STs. The strains from imported food products in CC398, CC7, CC30, CC12, and CC188 had far distances from Chinese strains in the tree. Conclusions: In this study, the predominant clone complexes of food-borne strains were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, which overlapped with the previously reported clone complexes of hospital and community-associated strains in China, suggesting that close attention needs to be paid to food, a vehicle of pathogen transmission in community and food poisoning.

Prediction of superantigen active sites and clonal expression of staphylococcal enterotoxin-like W / 中华流行病学杂志

Objective: The docking and superantigen activity sites of staphylococcal enterotoxin-like W (SElW) and T cell receptor (TCR) were predicted, and its SElW was cloned, expressed and purified. Methods: AlphaFold was used to predict the 3D structure of SElW protein monomers, and the protein models were evaluated with the help of the SAVES online server from ERRAT, Ramachandran plot, and Verify_3D. The ZDOCK server simulates the docking conformation of SElW and TCR, and the amino acid sequences of SElW and other serotype enterotoxins were aligned. The primers were designed to amplify selw, and the fragment was recombined into the pMD18-T vector and sequenced. Then recombinant plasmid pMD18-T was digested with BamHⅠand Hind Ⅲ. The target fragment was recombined into the expression plasmid pET-28a(+). After identification of the recombinant plasmid, the protein expression was induced by isopropyl-beta-D- thiogalactopyranoside. The SElW expressed in the supernatant was purified by affinity chromatography and quantified by the BCA method. Results: The predicted three-dimensional structure showed that the SElW protein was composed of two domains, the amino-terminal and the carboxy-terminal. The amino-terminal domain was composed of 3 α-helices and 6 β-sheets, and the carboxy-terminal domain included 2 α-helices and 7 antiparallel β-sheets composition. The overall quality factor score of the SElW protein model was 98.08, with 93.24% of the amino acids having a Verify_3D score ≥0.2 and no amino acids located in disallowed regions. The docking conformation with the highest score (1 521.328) was selected as the analysis object, and the 19 hydrogen bonds between the corresponding amino acid residues of SElW and TCR were analyzed by PyMOL. Combined with sequence alignment and the published data, this study predicted and found five important superantigen active sites, namely Y18, N19, W55, C88, and C98. The highly purified soluble recombinant protein SElW was obtained with cloning, expression, and protein purification. Conclusions: The study found five superantigen active sites in SElW protein that need special attention and successfully constructed and expressed the SElW protein, which laid the foundation for further exploration of the immune recognition mechanism of SElW.

Analysis and prospects of common problems in clinical data mining of traditional Chinese medicine prescriptions / 中国中药杂志

Mining data from traditional Chinese medicine(TCM) prescriptions is one of the important methods for inheriting the experience of famous doctors and developing new drugs. However, current research work has problems such as to be optimized research plans and non-standard statistics. The main problems and corresponding solutions summarized by the research mainly include four aspects.(1)The research plan design needs to consider the efficacy and quality of individual cases.(2)The significance of the difference in confidence order of association rules needs to be further considered, and the lift should not be ignored.(3)The clustering analysis steps are complex. The selection of clustering variables should comprehensively consider factors such as the frequency of TCM, network topology parameters, and practical application significance. The selection of distance calculation and clustering methods should be improved based on the characteristics of TCM clinical data. Jaccard distance and its improvement plan should be given attention in the future. A single, unexplained clustering result should not be presented, but the final clustering plan should be selected based on a comprehensive consideration of TCM clinical characteristics and objective evaluation indicators for clustering.(4)When calculating correlation coefficients, algorithms that are only suitable for continuous variables should not be applied to binary variables. This article explained the connotations of the above problems based on the characteristics of TCM clinical research and statistical principles and proposed corresponding suggestions to provide important references for future data mining research work.

Neuroendocrine-Immune Regulatory Network of Eucommia ulmoides Oliver.

Eucommia ulmoides Oliver (E. ulmoides) is a popular medicinal herb and health supplement in China, Japan, and Korea, and has a variety of pharmaceutical properties. The neuroendocrine-immune (NEI) network is crucial in maintaining homeostasis and physical or psychological functions at a holistic level, consistent with the regulatory theory of natural medicine. This review aims to systematically summarize the chemical compositions, biological roles, and pharmacological properties of E. ulmoides to build a bridge between it and NEI-associated diseases and to provide a perspective for the development of its new clinical applications. After a review of the literature, we found that E. ulmoides has effects on NEI-related diseases including cancer, neurodegenerative disease, hyperlipidemia, osteoporosis, insomnia, hypertension, diabetes mellitus, and obesity. However, clinical studies on E. ulmoides were scarce. In addition, E. ulmoides derivatives are diverse in China, and they are mainly used to enhance immunity, improve hepatic damage, strengthen bones, and lower blood pressure. Through network pharmacological analysis, we uncovered the possibility that E. ulmoides is involved in functional interactions with cancer development, insulin resistance, NAFLD, and various inflammatory pathways associated with NEI diseases. Overall, this review suggests that E. ulmoides has a wide range of applications for NEI-related diseases and provides a direction for its future research and development.

ß-Hydroxybutyrate in Cardiovascular Diseases : A Minor Metabolite of Great Expectations.

Despite recent advances in therapies, cardiovascular diseases ( CVDs ) are still the leading cause of mortality worldwide. Previous studies have shown that metabolic perturbations in cardiac energy metabolism are closely associated with the progression of CVDs. As expected, metabolic interventions can be applied to alleviate metabolic impairments and, therefore, can be used to develop therapeutic strategies for CVDs. ß-hydroxybutyrate (ß-HB) was once known to be a harmful and toxic metabolite leading to ketoacidosis in diabetes. However, the minor metabolite is increasingly recognized as a multifunctional molecular marker in CVDs. Although the protective role of ß-HB in cardiovascular disease is controversial, increasing evidence from experimental and clinical research has shown that ß-HB can be a "super fuel" and a signaling metabolite with beneficial effects on vascular and cardiac dysfunction. The tremendous potential of ß-HB in the treatment of CVDs has attracted many interests of researchers. This study reviews the research progress of ß-HB in CVDs and aims to provide a theoretical basis for exploiting the potential of ß-HB in cardiovascular therapies.

Contralesional Sensorimotor Network Participates in Motor Functional Compensation in Glioma Patients.

Background: Some gliomas in sensorimotor areas induce motor deficits, while some do not. Cortical destruction and reorganization contribute to this phenomenon, but detailed reasons remain unclear. This study investigated the differences of the functional connectivity and topological properties in the contralesional sensorimotor network (cSMN) between patients with motor deficit and those with normal motor function. Methods: We retrospectively reviewed 65 patients (32 men) between 2017 and 2020. The patients were divided into four groups based on tumor laterality and preoperative motor status (deficit or non-deficit). Thirty-three healthy controls (18 men) were enrolled after matching for sex, age, and educational status. Graph theoretical measurement was applied to reveal alterations of the topological properties of the cSMN by analyzing resting-state functional MRI. Results: The results for patients with different hemispheric gliomas were similar. The clustering coefficient, local efficiency, transitivity, and vulnerability of the cSMN significantly increased in the non-deficit group and decreased in the deficit group compared to the healthy group (p < 0.05). Moreover, the nodes of the motor-related thalamus showed a significantly increased nodal efficiency and nodal local efficiency in the non-deficit group and decreased in the deficit group compared with the healthy group (p < 0.05). Conclusions: We posited the existence of two stages of alterations of the preoperative motor status. In the compensatory stage, the cSMN sacrificed stability to acquire high efficiency and to compensate for impaired motor function. With the glioma growing and the motor function being totally damaged, the cSMN returned to a stable state and maintained healthy hemispheric motor function, but with low efficiency.

Developmental transcriptomics throughout the embryonic developmental process of Rhipicephalus turanicus reveals stage-specific gene expression profiles.

BACKGROUND: Ticks are important vectors and transmit diverse pathogens, including protozoa, viruses, and bacteria. Tick-borne diseases can cause damage to both human health and the livestock industries. The control and prevention of ticks and tick-borne diseases has relied heavily on acaricides. METHODS: In the present study, using a high-throughput RNA sequencing (RNA-Seq) technique, we performed a comprehensive time-series transcriptomic analysis throughout the embryogenesis period of Rhipicephalus turanicus. RESULTS: Altogether, 127,157 unigenes were assembled and clustered. Gene expression differences among the embryonic stages demonstrated that the most differentially expressed genes (DEGs) were observed in the comparisons of early embryonic stages (RTE5 vs. RTE10, 9726 genes), and there were far fewer DEGs in later stages (RTE25 vs. RTE30, 2751 genes). Furthermore, 16 distinct gene modules were identified according to weighted gene co-expression network analysis (WGCNA), and genes in different modules displayed stage-specific characteristics. Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment suggested that some genes involved in organ and tissue formation were significantly upregulated in the early embryonic developmental stages, whereas metabolism-related pathways were more enriched in the later embryonic developmental stages. CONCLUSIONS: These transcriptome studies revealed gene expression profiles at different stages of embryonic development, which would be useful for interrupting the embryonic development of ticks and disrupting the transmission of tick-borne diseases.

Computation of Antigenicity Predicts SARS-CoV-2 Vaccine Breakthrough Variants

It has been reported that multiple SARS-CoV-2 variants of concerns (VOCs) including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) can reduce neutralisation by antibodies, resulting in vaccine breakthrough infections. Virus-antiserum neutralisation assays are typically performed to monitor potential vaccine breakthrough strains. However, such experimental-based methods are slow and cannot instantly validate whether newly emerging variants can break through current vaccines or therapeutic antibodies. To address this, we sought to establish a computational model to predict the antigenicity of SARS-CoV-2 variants by sequence alone and in real time. In this study, we firstly identified the relationship between the antigenic difference transformed from the amino acid sequence and the antigenic distance from the neutralisation titres. Based on this correlation, we obtained a computational model for the receptor binding domain (RBD) of the spike protein to predict the fold decrease in virus-antiserum neutralisation titres with high accuracy (~0.79). Our predicted results were comparable with experimental neutralisation titres of variants, including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), B.1.429 (Epsilon), P.1 (Gamma), B.1.526 (Iota), B.1.617.1 (Kappa), and C.37 (Lambda), as well as SARS-CoV. Here, we firstly predicted the fold of decrease of B.1.1.529 (Omicron) as 17.4-fold less susceptible to neutralisation. We visualised all 1521 SARS-CoV-2 lineages to indicate variants including B.1.621 (Mu), B.1.630, B.1.633, B.1.649, and C.1.2, which can induce vaccine breakthrough infections in addition to reported VOCs B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Our study offers a quick approach to predict the antigenicity of SARS-CoV-2 variants as soon as they emerge. Furthermore, this approach can facilitate future vaccine updates to cover all major variants. An online version can be accessed at http://jdlab.online.

COVID-19 lesion detection and segmentation-A deep learning method.

PURPOSE: In this paper, we utilized deep learning methods to screen the positive COVID-19 cases in chest CT. Our primary goal is to supply rapid and precise assistance for disease surveillance on the medical imaging aspect. MATERIALS AND METHODS: Basing on deep learning, we combined semantic segmentation and object detection methods to study the lesion performance of COVID-19. We put forward a novel end-to-end model which takes advantage of the Spatio-temporal features. Furthermore, a segmentation model attached with a fully connected CRF was designed for a more effective ROI input. RESULTS: Our method showed a better performance across different metrics against the comparison models. Moreover, our strategy highlighted strong robustness for the processed augmented testing samples. CONCLUSION: The comprehensive fusion of Spatio-temporal correlations can exploit more valuable features for locating target regions, and this mechanism is friendly to detect tiny lesions. Although it remains in discrete form, the feature extracting in temporal dimension improves the precision of final prediction.

Anti-tumor activity of yeast vesicle biomimetic nanomedicine with the ability of active tumor penetration / 药学学报

The dense extracellular matrix (ECM) of the tumor severely limits the deep penetration of nanomedicine and weakens its anti-tumor effect. Based on this, the yeast vesicle biomimetic nanomedicine with active deep penetration ability of tumor tissue was designed and developed for enhanced tumor therapy. Results of characterization showed that the yeast cell vesicles (YCV) displayed a spherical morphology with diameter of around 100 nm and was well dispersed. Then the chemotherapeutic drug doxorubicin (DOX) was selected as a model drug, and DOX was loaded into YCV to obtain YCV/DOX through electrostatic interaction, the encapsulation efficiencies of DOX were calculated as 82.5%. The drug release profile of YCV/DOX implied that DOX release showed a manner of pH-dependent, it may be that pH has affected the electrostatic effect of YCV and DOX. Compared with liposomes (Lipo), in vitro cell experiments showed that YCV from natural sources had stronger permeability in three-dimensional multicellular spheres. It is speculated that the mechanism may be good deformation capacity of YCV. A 4T1 xenograft tumor model was established to evaluate the therapeutic efficacy of YCV/DOX. The results suggested that YCV/DOX has stronger tumor tissue penetration ability and could effectively inhibit the tumor growth. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Zhengzhou University. This study brings new ideas for the development of biomimetic nanomedicine to overcome the ECM of solid tumors.

Reconstruction of multiple metatarsus and soft tissue defects with fibular flap and fibular artery chimeric: A case report / 中华显微外科杂志

In May 2019, a patient who suffered with multiple foot metatarsus injury with soft tissues defect was treated in the Hand and Foot Microsurgery of Xi'an Fengcheng Hospital, by using chimeric peroneal artery for phase-1 reconstruction of metatarsus with folded fibular flap, foot cross arch and soft tissue defects. After 2 years, the arch of foot as intact without collapse. There was no arthritic lesions. The height, arc and width of metatarsus were very close to the healthy side. The flap and plantar were smooth without abrasion and ulceration. The patient could walk, run and stand with single-foot stand, and able to carry out heavy physical work continuously.