Association of Lipoprotein(a) Levels With Myocardial Infarction in Patients With Low-Attenuation Plaque.

BACKGROUND: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. OBJECTIVES: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). METHODS: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. RESULTS: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. CONCLUSIONS: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.

Berberine directly targets AKR1B10 protein to modulate lipid and glucose metabolism disorders in NAFLD.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberine (BBR) is the main active component from Coptidis rhizome, a well-known Chinese herbal medicine used for metabolic diseases, especially diabetes for thousands of years. BBR has been reported to cure various metabolic disorders, such as nonalcoholic fatty liver disease (NAFLD). However, the direct proteomic targets and underlying molecular mechanism of BBR against NAFLD remain less understood. AIM OF THE STUDY: To investigate the direct target and corresponding molecular mechanism of BBR on NAFLD is the aim of the current study. MATERIALS AND METHODS: High-fat diet (HFD)-fed mice and oleic acid (OA) stimulated HepG2 cells were utilized to verify the beneficial impacts of BBR on glycolipid metabolism profiles. The click chemistry in proteomics, DARTS, CETSA, SPR and fluorescence co-localization analysis were conducted to identify the targets of BBR for NAFLD. RNA-seq and shRNA/siRNA were used to investigate the downstream pathways of the target. RESULTS: BBR improved hepatic steatosis, ameliorated insulin resistance, and reduced TG levels in the NAFLD models. Importantly, Aldo-keto reductase 1B10 (AKR1B10) was first proved as the target of BBR for NAFLD. The gene expression of AKR1B10 increased significantly in the NAFLD patients' liver tissue. We further demonstrated that HFD and OA increased AKR1B10 expression in the C57BL/6 mice's liver and HepG2 cells, respectively, whereas BBR decreased the expression and activities of AKR1B10. Moreover, the knockdown of AKR1B10 by applying shRNA/siRNA profoundly impacted the beneficial effects on the pathogenesis of NAFLD by BBR. Meanwhile, the changes in various proteins (ACC1, CPT-1, GLUT2, etc.) are responsible for hepatic lipogenesis, fatty acid oxidation, glucose uptake, etc. by BBR were reversed by the knockdown of AKR1B10. Additionally, RNA-seq was used to identify the downstream pathway of AKR1B10 by examining the gene expression of liver tissues from HFD-fed mice. Our findings revealed that BBR markedly increased the protein levels of PPARα while downregulating the expression of PPARγ. However, various proteins of PPAR signaling pathways remained unaffected post the knockdown of AKR1B10. CONCLUSIONS: BBR alleviated NAFLD via mediating PPAR signaling pathways through targeting AKR1B10. This study proved that AKR1B10 is a novel target of BBR for NAFLD treatment and helps to find new targets for the treatment of NAFLD by using active natural compounds isolated from traditional herbal medicines as the probe.

On-line monitoring of membrane fouling based on an improved electrical measurement method.

On-line monitoring of membrane fouling is essential in the water treatment process. Drawbacks such as low-sensitivity and off-line limitations limit the application of existing methods. An on-line monitoring method based on Electrical Resistance Tomography (ERT) sensors is put forward in this paper. The Particle Swarm Optimization with Simulated Annealing (PSO-SA) algorithm is used in optimizing the topologies of finite element models in order to decrease the ill-posedness of sensitivity matrices. The deep denoising extreme learning machine with an auto-encoder model and the K-singular value decomposition algorithm are used in ERT reconstruction to improve imaging quality. The lift-wavelet is adopted in measuring the permeate flux to improve measuring accuracy. The ERT pixel values of the membrane module and the result of flux are used to analyze the fouling status. The results of membrane fouling experiments demonstrate the following: (1) Based on the local ERT pixels, the "two stage" phenomenon of membrane fouling can be observed. (2) In the early stage, the fouling distribution of the localized membrane module is consistent with its ERT pixels. (3) The deposition process of foulants for the localized membrane module is synchronized with the variation of ERT pixels. (4) The integrity of the membrane module can be detected according to the ERT pixels. Therefore, the novel method can effectively reflect the membrane fouling process, especially in the early stages of membrane fouling.

Case Report: COVID-19 exacerbates acute lower limb ischemia in patients with popliteal artery entrapment syndrome.

Non-traumatic lower limb ischemic diseases are extremely rare among young people. Clinically, they are mainly seen in the form of popliteal artery entrapment syndrome (PAES). In addition, with the prevalence of COVID-19 infection, more and more studies report that COVID-19 infection may lead to arteriovenous thrombosis, which could cause lower limb ischemia. This case reported that a 31-year-old male amateur football player who developed intermittent claudication after recovering from COVID-19. After 2 months of consultation, he was ultimately diagnosed with PAES. As is well known, PAES is mostly caused by long-term compression of the popliteal artery by abnormal anatomical structures, resulting in thickening of the vascular outer membrane and progression of the disease until intimal damage and thrombosis, leading to lower limb ischemia. During the progression of the disease, there may be multiple factors that accelerate its progression. Therefore, combined with the patient's clinical history and related studies on confirmed thrombosis caused by COVID-19, we can infer that COVID-19 could accelerate the occurrence of PAES.

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment.

A library of novel bis-Schiff base derivatives based on thiobarbituric acid has been effectively synthesized by multi-step reactions as part of our ongoing pursuit of novel anti-diabetic agents. All these derivatives were subjected to in vitro α-glucosidase inhibitory potential testing after structural confirmation by modern spectroscopic techniques. Among them, compound 8 (IC50 = 0.10 ± 0.05 µM), and 9 (IC50 = 0.13 ± 0.03 µM) exhibited promising inhibitory activity better than the standard drug acarbose (IC50 = 0.27 ± 0.04 µM). Similarly, derivatives (5, 6, 7, 10 and 4) showed significant to good inhibitory activity in the range of IC50 values from 0.32 ± 0.03 to 0.52 ± 0.02 µM. These derivatives were docked with the target protein to elucidate their binding affinities and key interactions, providing additional insights into their inhibitory mechanisms. The chemical nature of these compounds were reveal by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-311++G(d,p) basis set. The presence of intramolecular H-bonding was explored by DFT-d3 and reduced density gradient (RGD) analysis. Furthermore, various reactivity parameters were explored by performing TD-DFT at CAM-B3LYP/6-311++G(d,p) method.

Regulation of Mycobacterium biofilm development and novel measures against antibiotics resistance.

Currently, there are over 170 recognized species of Mycobacterium, the only genus in the family Mycobacteriaceae. Organisms belonging to this genus are quite diverse with respect to their ability to cause disease in humans. The Mycobacterium genus includes human pathogens (Mycobacterium tuberculosis complex and Mycobacterium leprae) and environmental microorganisms known as non-tuberculosis mycobacteria (NTM). A common pathogenic factor of Mycobacterium is the formation of biofilms. Bacterial biofilms are usually defined as bacterial communities attached to the surface, and are also considered as shared spaces of encapsulated microbial cells, including various extracellular polymeric substrates (EPS), such as polysaccharides, proteins, amyloid proteins, lipids, and extracellular DNA (EDNA), as well as membrane vesicles and humic like microorganisms derived refractory substances. The assembly and dynamics of the matrix are mainly coordinated by second messengers, signaling molecules, or small RNAs. Fully deciphering how bacteria provide structure for the matrix, thereby promoting extracellular reactions and benefiting from them, remains a challenge for future biofilm research. This review introduces a five step development model for biofilms and a new model for biofilm formation, analyses the pathogenicity of biofilms, their interactions with bacteriophages and host immune cells, and the key genes and regulatory networks of mycobacterial biofilms, as well as mycobacterial biofilms and drug resistance, in order to provide a basis for clinical treatment of diseases caused by biofilms.

Clinical features, risk factors and treatment of type 2 diabetes mellitus in patients with acute exacerbation of chronic obstructive pulmonary disease / 中国临床药理学与治疗学

AIM: To investigate the clinical features of acute exacerbation chronic obstructive pulmonary disease (AECOPD) of complicated with type 2 diabetes mellitus (T2DM), and analyze the related clinical features and risk factors. METHODS: This was a single-center cross-sectional study. From March 2020 to January 2023, 479 hospitalized patients with AECOPD in the department of respiratory and critical care medicine, Suining Central Hospital were included. There were 215 patients in AECOPD group and 60 patients in AECOPD with T2DM group. The collected variables included demographic data, complications, blood routine, infection index, random blood glucose, blood gas analysis and lung function. The adoption rate and constituent ratio of the basic description classification data were expressed as mean standard deviation for the normal distribution measurement data and median interquartile range for the skew distribution measurement data. T-test was used for normal distribution and non - parameter test was used for non-normal distribution. The categorical variables were tested by chi-square test. Rank sum test was used for rank variable data. Binary logistic regression model was used to investigate the independent factors associated with T2DM in patients with AECOPD. Finally, the results of logistic regression were verified and visualized by nomogram, validation curve, ROC curve and DCA curve. P0.05). The results of logistic regression were verified and visualized by Nomogram and its-associated ccurves. The MAE and AUC curves were 0.021 and 0.847 respectively, indicating that the model had good prediction consistency and accuracy. The DCA curve showed that Nomogram's risk threshold ranged from 0.01 to 0.99, suggesting that nomogram's model had better clinical predictive value. CONCLUSION: Our results showed that increased BMI, PaCO2 and random glucose, decreased blood lymphocyte, and atrial fibrillation is an independent clinical feature of AECOPD with T2DM. These results suggest that the immune function of patients with AECOPD and T2DM are more severely impaired and more likely to be accompanied by atrial fibrillation, which is a potential cause of poor prognosis in these patients. Meanwhile, this conclusion needs to be further verified in multicenter study with large sample size.

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine：Aural Vertigo / 中国实验方剂学杂志

Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine （TCM） mainly involves peripheral vestibular diseases of Western medicine， such as Meniere's disease， benign paroxysmal positional vertigo， vestibular neuritis， and vestibular migraine， being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo， aural vertigo affecting the quality of life， aural vertigo not relieved after surgery， aural vertigo with complex causes， and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM： Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo， the control and mitigation of the symptoms， and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.

Effect of Baihe Yuzi Prescription on CFTR， AQP， and ZIP Ion Channels and Oxidative Stress in Epididymis of Oligoasthenozoospermia Rats / 中国实验方剂学杂志

ObjectiveTo observe the effects of Baihe Yuzi prescription （BYP） on the cystic fibrosis transmembrane conductance regulator （CFTR）， aquaporin （AQP）， zinc/iron-regulated transporter-like protein （ZIP） and local oxidative stress in epididymis of oligoasthenozoospermia （OAS） rats， and to explore the mechanism of its intervention in OAS. MethodAfter 35 rats were acclimatized for 1 week， 7 rats were randomly selected as the normal group， and the remaining 28 rats were given tripterygium glycosides （TG） 30 mg·kg-1. After 4 weeks of modeling， they were randomly divided into 4 groups： model group， BYP low-dose group （LBYP）， BYP high-dose group （HBYP） and levocarnitine group， with 7 rats in each group. The rats in the normal group and model group were given normal saline at the same dosage. The levocarnitine group rats were given L-carnitine oral liquid （100 mg·kg-1） by gavage. The LBYP group rats were given BYP 6.3 g·kg-1， and the HBYP group rats were given BYP 12.6 g·kg-1 by gavage once a day for consecutive 4 weeks. After the end of the intervention， sperm count and motility of all rats were detected， the histopathological structure of epididymis was observed by hematoxylin-eosin （HE） staining， and the expressions of CFTR， AQP9， AQP3， ZIP8， ZIP12 and other proteins were detected by Western blot. The contents of α-glycosidase （α-GC）， sialic acid （SA）， carnitine， superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） were detected by enzyme-linked immunosorbent assay （ELISA）. Total zinc content was measured using an inductively coupled plasma mass spectrometer. Free zinc ion content was detected by zinc ion probes. ResultCompared with those in the normal group， the sperm count and motility of rats were decreased and the epididymal structure was disordered in the model group. The contents of α-GC and carnitine were decreased in epididymis （P<0.05）. MDA levels were increased， while SOD， GSH-Px and zinc levels were decreased （P<0.05）. The expressions of CFTR and ZIP12 in the head and cauda of the epididymis were down-regulated， and AQP3 expression was up-regulated. The expression of ZIP8 in the cauda epididymis was up-regulated （P<0.05）. Compared with the model group， BYP can significantly improve the sperm count and motility， the epididymal structure of OAS rats and the levels of α-GC and carnitine （P<0.05）. The expressions of CFTR and ZIP12 in the head and cauda of the epididymis were up-regulated， while the expressions of ZIP8 in the cauda epididymis and AQP3 in the head of the epididymis were decreased （P<0.05）. The SOD and GSH-Px levels and total zinc content in epididymis were increased， and the MDA levels were decreased （P<0.05）. ConclusionBYP may improve the sperm quality and repair epididymal tissue structure and function of OAS rats， by regulating the expressions of CFTR， AQP3， and ZIP12 ion channels and local antioxidant mechanism.

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition) / 中草药·英文版

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Research progress on valgus impacted proximal humeral fractures / 中国修复重建外科杂志

OBJECTIVE@#To review the advancement made in the understanding of valgus impacted proximal humeral fracture (PHF).@*METHODS@#The domestic and foreign literature about the valgus impacted PHF was extensively reviewed and the definition, classification, pathological features, and treatment of valgus impacted PHFs were summarized.@*RESULTS@#PHF with a neck shaft angle ≥160° is recognized as a valgus impacted PHF characterized by the preservation of the medial epiphyseal region of the humeral head, which contributes to maintenance of the medial periosteum's integrity after fracture and reduces the occurrence of avascular necrosis. Therefore, the valgus impacted PHF has a better prognosis when compared to other complex PHFs. The Neer classification designates it as a three- or four-part fracture, while the AO/Association for the Study of Internal Fixation (AO/ASIF) categorizes it as type C (C1.1). In the management of the valgus impacted PHF, the selection between conservative and surgical approaches is contingent upon the patient's age and the extent of fracture displacement. While conservative treatment offers the advantage of being non-invasive, it is accompanied by limitations such as the inability to achieve anatomical reduction and the potential for multiple complications. Surgical treatment includes open reduction combined with steel wire or locking plate and/or non-absorbable suture, transosseous suture technology, and shoulder replacement. Surgeons must adopt personalized treatment strategies for each patient with a valgus impacted PHF. Minimally invasive surgery helps to preserve blood supply to the humeral head, mitigate the likelihood of avascular necrosis, and reduce postoperative complications of bone and soft tissue. For elderly patients with severe comminuted and displaced fractures, osteoporosis, and unsuitable internal fixation, shoulder joint replacement is the best treatment option.@*CONCLUSION@#Currently, there has been some advancement in the classification, vascular supply, and management of valgus impacted PHF. Nevertheless, further research is imperative to assess the clinical safety, biomechanical stability, and indication of minimally invasive technology.

The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19.

The global coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on global social and economic development and human health. By combining traditional Chinese medicine (TCM) with modern medicine, the Chinese government has protected public health by supporting all phases of COVID-19 prevention and treatment, including community prevention, clinical treatment, control of disease progression, and promotion of recovery. Modern medicine focuses on viruses, while TCM focuses on differential diagnosis of patterns associated with viral infection of the body and recommends the use of TCM decoctions for differential treatment. This differential diagnosis and treatment approach, with its profoundly empirical nature and holistic view, endows TCM with an accessibility advantage and high application value for dealing with COVID-19. Here, we summarize the advantage of and evidence for TCM use in COVID-19 prevention and treatment to draw attention to the scientific value and accessibility advantage of TCM and to promote the use of TCM in response to public health emergencies. Please cite this article as: Huang M, Liu YY, Xiong K, Yang FW, Jin XY, Wang ZQ, Zhang JH, Zhang BL. The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19. J Integr Med. 2023; 21(5): 407-412.

A Scd1-mediated metabolic alteration participates in liver responses to low-dose bavachin.

Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs, such as bavachin (BV) in Fructus Psoraleae, has a prolonged latency to overt drug-induced liver injury in the clinic. Several studies have described BV-induced liver damage and underlying toxicity mechanisms, but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level, and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase, making it much harder for early recognition of hepatotoxicity. Here, we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests, but found subtle steatosis in BV-treated hepatocytes. We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver. Among these, the hepa3 subtype suffered from a vast alteration in lipid metabolism, which was characterized by enhanced expression of apolipoproteins, carboxylesterases, and stearoyl-CoA desaturase 1 (Scd1). In particular, increased Scd1 promoted monounsaturated fatty acids (MUFAs) synthesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids (PUFAs) generation, which participates in the initiation of ferroptosis. Additionally, we demonstrated that multiple intrinsic transcription factors, including Srebf1 and Hnf4a, and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes. Collectively, our study deciphered the features of hepatocytes in response to BV insult, decoded the underlying molecular mechanisms, and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.

Activity Changes of the Peptic Lactoferrin Hydrolysate in Human Gastric Cancer AGS Cells in Response to Cu(II) or Mn(II) Addition.

Lactoferrin is an interesting bioactive protein in milk and can interact with various metal ions of trace elements such as copper, iron, manganese, and others. In this study, a lactoferrin hydrolysate (LFH) was generated from commercial bovine lactoferrin by protease pepsin, fortified with Cu2+ (or Mn2+) at two levels of 0.64 and 1.28 (or 0.28 and 0.56) mg/g protein, respectively, and then measured for the resultant bioactivity changes in the well-differentiated human gastric cancer AGS cells. The assaying results indicated that the LFH and Cu/Mn-fortified products had long-term anti-proliferation on the cells, while the treated cells showed DNA fragmentation and increased apoptotic cell proportions. Regarding the control cells, the cells treated with the LFH and especially Cu/Mn-fortified LFH had remarkably up-regulated mRNA expression of caspase-3 and Bax by respective 1.21-3.23 and 2.23-2.83 folds, together with down-regulated mRNA expression Bcl-2 by 0.88-0.96 folds. Moreover, Western-blot assaying results also indicated that the cells exposed to the LFH and Cu/Mn-fortified LFH (especially Mn at higher level) for 24 h had an enhanced caspase-3 expression and increased ratio of Bax/Bcl-2. It can thus be concluded that the used Cu/Mn-addition to the LFH may lead to increased bioactivity in the AGS cells; to be more specific, the two metal ions at the used addition levels could endow LFH with a higher ability to cause cell apoptosis by activating caspase-3 and increasing the Bax/Bcl-2 ratio.

Empirical study on the construction of a cognitive model of factorization in eighth-grade students.

The construction of cognitive models is the basis for cognitive diagnosis, and the cognitive models will change based on the purpose of the study. According to the purpose of mathematical education, the cognitive factorization model is constructed based on the competence and knowledge dimensions. The factorization cognitive model was preliminarily constructed using expert-defined and literature surveys, and a small-scale test was subsequently carried out. The rationality of the cognitive model was tested through verbal reports and the regression of the item's difficulty through the cognitive attributes. The study included a sample of 72 students from two eighth-grade classes in a junior high school located in Wuhan. A diagnosis was made based on the mastery of factorization knowledge and the level of mathematical operation ability of the eighth graders in the cognitive model. Research 1 demonstrates that the construction of the cognitive factorization model is reasonable. Research 2 shows that approximately 79% of students' mathematics operation ability can reach the level of knowledge understanding, 71% of students can reach the level of knowledge transfer, and only 28% of students can reach the level of knowledge innovation.

Identification of several inflammation-related genes based on bioinformatics and experiments.

BACKGROUND: Osteoarthritis (OA) is a common disease of elderly individuals, with an unclear pathogenesis and limited treatment options to date. Inflammation occurs prominently in osteoarthritis, thereby making anti-inflammatory treatments promising in clinical outcomes. Therefore, it is of diagnostic and therapeutic significance to explore more inflammatory genes. METHOD: In this study, appropriate datasets were first acquired through gene set enrichment analysis (GSEA), followed by inflammation-related genes through weighted gene coexpression network analysis (WGCNA). Two machine learning algorithms (random forest-RF and support vector machine-recursive feature elimination, SVM-RFE) were used to capture the hub genes. In addition, two genes negatively associated with inflammation and osteoarthritis were identified. Afterwards, these genes were verified through experiments and network pharmacology. Due to the association between inflammation and many diseases, the expression levels of the above genes in various inflammatory diseases were determined through literature and experiments. RESULT: Two hub genes closely related to osteoarthritis and inflammation were obtained, namely, lysyl oxidase-like 1 (LOXL1) and pituitary tumour-transforming gene (PTTG1), which were shown to be highly expressed in osteoarthritis according to the literature and experiments. However, the expression levels of receptor expression-enhancing protein (REEP5) and cell division cycle protein 14B (CDC14B) remained unchanged in osteoarthritis. This finding was consistent with our verification from the literature and experiments that some genes were highly expressed in numerous inflammation-related diseases, while REEP5 and CDC14B were almost unchanged. Meanwhile, taking PTTG1 as an example, we found that inhibition of PTTG1 expression could suppress the expression of inflammatory factors and protect the extracellular matrix through the microtubule-associated protein kinase (MAPK) signalling pathway. CONCLUSIONS: LOXL1 and PTTG1 were highly expressed in some inflammation-related diseases, while that of REEP5 and CDC14B were almost unchanged. PTTG1 may be a potential target for the treatment of osteoarthritis.

AIWW: a new nutrition-screening tool for the oncologic population.

Malnutrition is a common comorbidity among patients with cancer. However, no nutrition-screening tool has been recognized in this population. A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed. Based on the previous 25 nutrition-screening tools, the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category. According to these results, we built a nutrition-screening tool named age, intake, weight, and walking (AIWW). Malnutrition was defined based on the scored patient-generated subjective global assessment (PG-SGA). Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW, nutritional risk screening 2002 (NRS-2002), and malnutrition screening tool (MST). Clinical benefit was calculated by the decision curve analysis (DCA), integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). A total of 11,360 patients (male, n=6,024 (53.0%) were included in the final study cohort, and 6,363 patients had malnutrition based on PG-SGA. Based on AIWW, NRS-2002, and MST, 7,545, 3,469, and 1,840 patients were at risk of malnutrition, respectively. The sensitivities of AIWW, NRS-2002, and MST risks were 0.910, 0.531, and 0.285, and the specificities were 0.768, 0.946, and 0.975. The Kendall tau coefficients of AIWW, NRS-2002, and MST risks were 0.588, 0.501, and 0.326, respectively. The area under the curve of AIWW, NRS-2002, and MST risks were 0.785, 0.739, and 0.630, respectively. The IDI, cNRI, and DCA showed that AIWW is non-inferior to NRS-2002 (IDI: 0.002 (-0.009, 0.013), cNRI: -0.015 (-0.049, 0.020)). AIWW scores can also predict the survival of patients with cancer. The missed diagnosis rates of AIWW, NRS-2002, and MST were 0.09%, 49.0%, and 73.2%, respectively. AIWW showed a better nutrition-screening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutrition-screening tool for this population.

Can the establishment of national sanitary cities better resist the impact of COVID-19?

The global spread of COVID-19 has led to profound reflection on building a global public health security system. This paper uses the urban data collected during the COVID-19 epidemic in China in 2020 to evaluate the effect of the National Sanitary City (NSC) policy on the prevention and control of that epidemic at different stages. We found that the NSC policy was able to curb the occurrence and transmission of the epidemic the epidemic effectively after controlling a series of factors such as urban characteristics, population mobility and pathogen transmission. Compared with non-NSCs, the NSCs were better able to control the number of infected people and the infection rate and transmission rate, and this performance was even more impressive when the epidemic gradually entered the sporadic distribution stage. The heterogeneity analysis shows that the impact of the NSC policy on the prevention and control of COVID-19 differs according to the economic development level and population size. To a certain extent, the NSC policy has blocked the spread of viruses by continuously improving the urban medical and health system and strengthening the publicity concerning infectious disease prevention and control knowledge.

The UDPase ENTPD5 regulates ER stress-associated renal injury by mediating protein N-glycosylation.

Impaired protein N-glycosylation leads to the endoplasmic reticulum (ER) stress, which triggers adaptive survival or maladaptive apoptosis in renal tubules in diabetic kidney disease (DKD). Therapeutic strategies targeting ER stress are promising for the treatment of DKD. Here, we report a previously unappreciated role played by ENTPD5 in alleviating renal injury by mediating ER stress. We found that ENTPD5 was highly expressed in normal renal tubules; however, ENTPD5 was dynamically expressed in the kidney and closely related to pathological DKD progression in both human patients and mouse models. Overexpression of ENTPD5 relieved ER stress in renal tubular cells, leading to compensatory cell proliferation that resulted in hypertrophy, while ENTPD5 knockdown aggravated ER stress to induce cell apoptosis, leading to renal tubular atrophy and interstitial fibrosis. Mechanistically, ENTPD5-regulated N-glycosylation of proteins in the ER to promote cell proliferation in the early stage of DKD, and continuous hyperglycemia activated the hexosamine biosynthesis pathway (HBP) to increase the level of UDP-GlcNAc, which driving a feedback mechanism that inhibited transcription factor SP1 activity to downregulate ENTPD5 expression in the late stage of DKD. This study was the first to demonstrate that ENTPD5 regulated renal tubule cell numbers through adaptive proliferation or apoptosis in the kidney by modulating the protein N-glycosylation rate in the ER, suggesting that ENTPD5 drives cell fate in response to metabolic stress and is a potential therapeutic target for renal diseases.