Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Neutrophil extracellular traps(NETs)are net-like complexes released by neutrophils and play a crucial role in antimicrobial defense. In addition, NETs can exacerbate inflammatory responses associated with various diseases, including diabetes, cardiovascular diseases, and autoimmune diseases. Currently, the role of NETs in ocular diseases has received extensive attention. This article systematically summarizes the formation mechanism of NETs and their role in maintaining intraocular homeostasis under physiological conditions. At the same time, it focuses on elaborating the pathogenic role of NETs in the field of ophthalmic diseases, such as dry eye, keratitis, uveitis, diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, emphasizing the importance of NETs as therapeutic targets for ocular diseases and the potential application value as new markers for ocular diseases. Future in-depth research on the mechanism of NETs in ocular diseases will provide a stronger theoretical basis for the treatment of related eye diseases.

ObjectiveTo study the effect and mechanism of fibrinogen （Fib） overexpression on mitochondrial quality control system in the rat model of coronary heart disease with the syndrome of blood stasis. MethodsForty male SD rats were randomly assigned into normal， model， Fib， and empty vector （AAV） groups， with 10 rats in each group. The model， Fib， and AAV groups were fed with a high-fat diet adaptively and administrated with 3×10⁶ U·kg^-1 vitamin D3 powder by gavage after 7 days and 2×10⁶ U·kg^-1 vitamin D3 solution after 14 days. After being fed with a high-fat diet for 7 weeks， rats in each group received subcutaneous injection of isoproterenol （5 mg·kg^-1） for 3 days. During the modeling period， rats in the normal group were fed with ordinary feed without any special treatment. The changes in blood lipid and hemorheological indexes of rats in each group were measured. The aorta tissue was stained with hematoxylin-eosin （HE）， and the standard lead Ⅱ electrocardiograms （ECGs） of rats in each group were recorded. Enzyme-linked immunosorbent assay （ELISA） and real-time PCR were employed to verify the overexpression levels of Fib in the liver and plasma. Western blotting was employed to determine the protein levels of mitofusin 2 （Mfn2）， optic atrophy protein 1 （OPA1）， dynamin-related protein 1 （Drp1）， phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）/adenosine monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor γ-coactivator-1α （PGC-1α）， PTEN-induced putative kinase 1， and Parkin. Real-time PCR was employed to determine the mRNA levels of AMPK and PGC-1α in the myocardial tissue. The changes in levels of adenosine triphosphate （ATP） and adenosine monophosphate （AMP） in the myocardial tissue were determined by ELISA. ResultsCompared with the normal group， the other three groups showed elevated levels of total cholesterol and low-density lipoprotein cholesterol （P<0.01） and no significant changes in levels of triglyceride and high-density lipoprotein cholesterol. Compared with the model group， the Fib and AAV groups showed risen levels of total cholesterol （P<0.05， P<0.01）. Compared with the normal group， the model and Fib groups presented increases in low shear viscosity and middle shear viscosity （P<0.05， P<0.01）， and the Fib group showcased an increase in high shear viscosity （P<0.01）. Compared with the model group， the Fib group showed increases in low shear viscosity， middle shear viscosity， and high shear viscosity （P<0.05， P<0.01）. Compared with the Fib group， the AAV group demonstrated decreases in low shear viscosity， middle shear viscosity， and high shear viscosity （P<0.05， P<0.01）. The normal group had an complete aortic structure with well arrangement of elastic fibers. In the model group， the vascular wall became thickened and the intima was rough with inflammatory infiltration. In the Fib group， the intima calcification formed a cavity structure and the intima was abnormally proliferated， while in the AAV group， the intima smooth muscle was slightly proliferated with local calcification. The ECG of the normal group indicated sinus rhythm， and that of the model group presented ST segment oblique elevation （>0.1 mV）. The ECG of the Fib group presented characteristic ST segment arch back elevation with T-wave towering， and that of the AAV group presented ST segment oblique elevation. Compared with the normal group， the model and Fib groups showed elevations in levels of liver Fib， plasma Fib， and liver Fibα mRNA （P<0.01）， and the AAV group had risen levels of Fib and Fibα mRNA （P<0.01）. Compared with the model group， the Fib group presented risen levels of liver Fib and Fibα mRNA （P<0.01）. Compared with the Fib group， the AAV group presented decreases in levels of liver Fib， plasma Fib， and liver Fibα mRNA （P<0.01）. Compared with the normal group， the other three groups had down-regulated protein and mRNA levels of Mfn2， OPA1， PINK1， Parkin， p-AMPK/AMPK， and PGC-1α （P<0.05， P<0.01） and up-regulated protein levels of Drp1 （P<0.01）. Compared with those in the model group， the mRNA and protein levels of Mfn2， OPA1， PINK1， Parkin， p-AMPK/AMPK， and PGC-1α were all down-regulated （P<0.05， P<0.01） and the protein level of Drp1 was up-regulated （P<0.01） in the Fib group. Compared with the Fib group， the AAV group showed differences in protein levels of OPA1， PGC-1α， Parkin， and Drp1 （P<0.05， P<0.01） and an increasing trend in the mRNA levels of AMPK and PGC-1α with no significant difference. Compared with the normal group， the other three groups had elevated levels of ATP in the myocardial tissue （P<0.01）. Compared with the model group， the Fib group showed elevated levels of ATP and AMP （P<0.01）. Compared with the Fib group， the AAV group exhibited lowered levels of ATP and AMP （P<0.01）. ConclusionFib can achieve the overexpression effect in the rat model of coronary heart disease with the syndrome of blood stasis. At the same time， the overexpression of Fib can induce the damage of the mitochondrial quality control system in the myocardial tissue， inhibit mitochondrial dynamics and mitochondrial biosynthesis， and down-regulate mitochondrial autophagy， thereby aggravating myocardial injury in the rat model.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

As a neglected tropical disease, schistosomiasis remains a major public health challenge in underdeveloped areas, notably Africa. Currently, the national schistosomiasis control programmes in Africa mainly depend on foreign aids; however, conventional international aid models have multiple limitations. To enhance the effectiveness and sustainability of global schistosomiasis control programmes, this article proposes a trinity collaboration model based on international rules, China’s experiences and local needs, which is explained with China aid project of schistosomiasis control in Zanzibar as an example. Based on the successful experiences from the national schistosomiasis control programme in China, this model emphasizes the compliance with World Health Organization guidelines and fully considers local actual needs to promote the effectiveness and sustainability of the schistosomiasis control programme through integrating international resources and promoting China’s experience to meet local needs. The successful practice of the China aid project of schistosomiasis control in Zanzibar provides strong evidence that the model is of great theoretical significance and practical value to improve the efficiency of multilateral collaboration and promote global health governance.

Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/10⁵, 95% UI: (1.49/10⁵, 4.07/10⁵)], prevalence [0.64/10⁵, 95% UI: (0.37/10⁵, 1.02/10⁵)], mortality [0.51/10⁵, 95% UI: (0, 1.80/10⁵)] and DALYs rates of VL [33.81/10⁵, 95% UI: (0.06/10⁵, 124.09/10⁵)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/10⁵, 95% UI: (0.45/10⁵, 0.72/10⁵); 0.14/10⁵, 95% UI: (0.11/10⁵, 0.18/10⁵)] than among women [0.27/10⁵, 95% UI: (0.21/10⁵, 0.33/10⁵); 0.06/10⁵, 95% UI: (0.05/10⁵, 0.08/10⁵)], and the highest mortality of VL was found among children under 5 years of age [0.24/10⁵, 95% UI: (0.08/10⁵, 0.66/10⁵)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/10⁵, 0.03/10⁵, 0.02/10⁵ and 1.44/10⁵ in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.

ObjectiveTo establish the multi-technique characteristic profiles of Alumen by X-ray diffraction（XRD）， Fourier-transform infrared spectroscopy（FTIR） and thermogravimetric-differential thermal analysis（TG-DTA）， and to explore the spectral characteristics for rapid identification of Alumen and its potential adulterant， Ammonium alum. MethodsA total of 27 batches of Alumen samples from 8 production regions were collected for preliminary identification based on visual characteristics. The PDF standard cards of XRD were used to differentiate Alumen from A. alum， and the XRD characteristic profiles of Alumen were established， and then the common peaks were screened. Based on hierarchical clustering analysis（HCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， the characteristic information that could be used for identification of Alumen was selected with variable importance in the projection（VIP） value>1. FTIR characteristic profiles of Alumen were established， and key wavenumbers for identification were screened by HCA and OPLS-DA with VIP value>1. Meanwhile， the thermogravimetric differences between Alumen and A. alum were analyzed by TG-DTA， and the thermogravimetric traits that could be used for identification were screened. ResultsAlumen and A. alum could not be effectively distinguished by traits alone. However， by comparing the PDF standard cards of XRD， 15 batches of Alumen and 12 batches of A. alum could be distinguished. In the XRD profiles， 10 characteristic peaks were confirmed， corresponding to diffraction angles of 14.560°， 24.316°， 12.620°， 32.122°， 17.898°， 34.642°， 27.496°， 46.048°， 40.697° and 21.973°. In the FTIR profiles， 4 wavenumber ranges（399.193-403.050， 1 186.010-1 471.420， 1 801.190-2 620.790， 3 612.020-3 997.710 cm^-1） and 12 characteristic wavenumbers（1 428.994， 1 430.922， 1 432.851， 1 434.779， 1 436.708， 1 438.636， 1 440.565， 1 442.493， 1 444.422， 1 446.350， 1 448.279， 1 450.207 cm^-1） were identified. In the TG-DTA profiles， there were characteristic decomposition peaks of ammonium ion and mass reduction features near 555.34 ℃ for A. alum. These characteristics could serve as important criteria for distinguishing the authenticity of Alumen. ConclusionXRD， FTIR and TG-DTA can be used to rapidly detect Alumen and A. alum， and combined with the discriminant features selected through chemometrics， the rapid and accurate identification of Alumen and A. alum can be achieved. The research findings provide new approaches for the rapid identification of Alumen.

ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

ObjectiveTo establish the multi-technique characteristic profiles of Alumen by X-ray diffraction（XRD）， Fourier-transform infrared spectroscopy（FTIR） and thermogravimetric-differential thermal analysis（TG-DTA）， and to explore the spectral characteristics for rapid identification of Alumen and its potential adulterant， Ammonium alum. MethodsA total of 27 batches of Alumen samples from 8 production regions were collected for preliminary identification based on visual characteristics. The PDF standard cards of XRD were used to differentiate Alumen from A. alum， and the XRD characteristic profiles of Alumen were established， and then the common peaks were screened. Based on hierarchical clustering analysis（HCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， the characteristic information that could be used for identification of Alumen was selected with variable importance in the projection（VIP） value>1. FTIR characteristic profiles of Alumen were established， and key wavenumbers for identification were screened by HCA and OPLS-DA with VIP value>1. Meanwhile， the thermogravimetric differences between Alumen and A. alum were analyzed by TG-DTA， and the thermogravimetric traits that could be used for identification were screened. ResultsAlumen and A. alum could not be effectively distinguished by traits alone. However， by comparing the PDF standard cards of XRD， 15 batches of Alumen and 12 batches of A. alum could be distinguished. In the XRD profiles， 10 characteristic peaks were confirmed， corresponding to diffraction angles of 14.560°， 24.316°， 12.620°， 32.122°， 17.898°， 34.642°， 27.496°， 46.048°， 40.697° and 21.973°. In the FTIR profiles， 4 wavenumber ranges（399.193-403.050， 1 186.010-1 471.420， 1 801.190-2 620.790， 3 612.020-3 997.710 cm^-1） and 12 characteristic wavenumbers（1 428.994， 1 430.922， 1 432.851， 1 434.779， 1 436.708， 1 438.636， 1 440.565， 1 442.493， 1 444.422， 1 446.350， 1 448.279， 1 450.207 cm^-1） were identified. In the TG-DTA profiles， there were characteristic decomposition peaks of ammonium ion and mass reduction features near 555.34 ℃ for A. alum. These characteristics could serve as important criteria for distinguishing the authenticity of Alumen. ConclusionXRD， FTIR and TG-DTA can be used to rapidly detect Alumen and A. alum， and combined with the discriminant features selected through chemometrics， the rapid and accurate identification of Alumen and A. alum can be achieved. The research findings provide new approaches for the rapid identification of Alumen.