Homo sapiens reached the higher latitudes of Europe by 45,000 years ago.

The Middle to Upper Palaeolithic transition in Europe is associated with the regional disappearance of Neanderthals and the spread of Homo sapiens. Late Neanderthals persisted in western Europe several millennia after the occurrence of H. sapiens in eastern Europe1. Local hybridization between the two groups occurred2, but not on all occasions3. Archaeological evidence also indicates the presence of several technocomplexes during this transition, complicating our understanding and the association of behavioural adaptations with specific hominin groups4. One such technocomplex for which the makers are unknown is the Lincombian-Ranisian-Jerzmanowician (LRJ), which has been described in northwestern and central Europe5-8. Here we present the morphological and proteomic taxonomic identification, mitochondrial DNA analysis and direct radiocarbon dating of human remains directly associated with an LRJ assemblage at the site Ilsenhöhle in Ranis (Germany). These human remains are among the earliest directly dated Upper Palaeolithic H. sapiens remains in Eurasia. We show that early H. sapiens associated with the LRJ were present in central and northwestern Europe long before the extinction of late Neanderthals in southwestern Europe. Our results strengthen the notion of a patchwork of distinct human populations and technocomplexes present in Europe during this transitional period.

The effect of the Litcubanine A on the treatment of murine experimental periodontitis by inhibiting monocyte-macrophage chemotaxis and osteoclast differentiation.

BACKGROUND: Periodontal disease is an inflammatory disease of periodontal tissues that is closely connected with systemic diseases. During periodontitis, the inappropriate recruitment and activation of monocytes-macrophages causes an increase in osteoclast activity and disrupts bone homeostasis. Therefore, it is a promising therapeutic strategy to treat periodontitis by regulating the functions of monocytes-macrophages. Litcubanine A (LA) is an isoquinoline alkaloid extracted from the traditional Chinese medicine Litsea cubeba, which was proven to have reproducible anti-inflammatory effects, but its regulatory role on bone homeostasis in periodontitis is still not clear. METHODS: In this study, zebrafish experiments and a mouse ligature-induced periodontitis model were performed, and histological analysis was used to investigate the effect of LA on macrophage chemotaxis under the inflammatory environment. Real-time PCR was used to detect the regulatory effect of LA (100 nM ~ 100 µM) on the chemotaxis function of macrophages induced by LPS. Apoptosis assay and flow cytometry were used to elucidate the influence of LA on macrophage apoptosis and proliferation. To further clarify the regulatory role of LA on macrophage osteoclast differentiation, real-time PCR, histological analysis, western blot, and micro-computed tomography (micro-CT) were performed in vivo and in vitro to verify the impact of LA on bone homeostasis. RESULTS: Compared with the control group, the chemotaxis function of macrophage was significantly attenuated by LA in vivo. LA could significantly inhibit the expression of genes encoding the chemokine receptors Ccr1 and Cxcr4, and its ligand chemokine Cxcl12 in macrophages, and suppresses the differentiation of osteoclastic precursors to osteoclasts through the MAPK signaling pathway. There were significantly lower osteoclast differentiation and bone loss in the LA group compared with the control in the ligature-induced periodontitis model. CONCLUSION: LA is a promising candidate for the treatment of periodontitis through its reproducible functions of inhibiting monocyte-macrophage chemotaxis and osteoclast differentiation.

The traditional Chinese medicines treat chronic heart failure and their main bioactive constituents and mechanisms.

Chronic heart failure (CHF) is a severe public health problem with increasing morbidity and mortality, any treatment targeting a single session is insufficient to tackle this. CHF is characterized by reduced cardiac output resulting from neurohumoral dysregulation and cardiac remodeling, which might be related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, autophagy, mitochondrial function, and angiogenesis. These molecular mechanisms interact with each other through crosstalk. Historically, Chinese medicinal herbs have been widely applied in the treatment of CHF, and therapeutic effects of Chinese medicinal herbs and their ingredients have been scientifically confirmed over the past decades. Traditional Chinese medicine (TCM) with multiple components can confront the different pathogenesis of CHF through multiple targets. This review analyzes commonly used TCM patent drugs and TCM decoctions that are applicable to different stages of CHF based on clinical trials. Diverse bioactive ingredients in Chinese medicinal herbs have been found to treat CHF via multiple molecular mechanisms. This review comprehensively covers the key works on the effects and underlying mechanisms of TCM, herbal ingredients and synergistic effects of constituent compatibility in treating CHF, providing additional ideas to address this threat.

[Advances in animal models of chronic heart failure and its applications in traditional Chinese medicine].

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.

[Pharmacological research progress of five classical prescriptions in treatment of chronic heart failure].

Chronic heart failure(CHF) is a comprehensive clinical syndrome caused by multiple factors that result in structural and/or functional abnormalities of the heart, leading to impaired ventricular contraction and/or relaxation functions. This medical condition represents the final stage of various cardiovascular diseases. In the treatment of CHF, multiple clinical studies have demonstrated the benefits of using traditional Chinese medicine(TCM) to control oxidative stress, inflammation, and apoptosis, thereby delaying ventricular remodeling and reducing myocardial fibrosis. In this study, common TCM syndromes in the diagnosis and treatment of CHF in recent years were reviewed and summarized. Five common treatment methods including benefiting Qi and activating blood circulation, enhancing Qi and nourishing Yin, warming Yang for diuresis, eliminating phlegm and dampness, rescuing from collapse by restoring Yang, and corresponding classic prescriptions in prevention and treatment of CHF were concluded under the guidance of TCM syndrome differentiation thinking. Meanwhile, research progress on the modern pharmacological effects of these classic prescriptions was systematically discussed, so as to establish a unique treatment system for CHF by classic prescriptions under the guidance of TCM syndrome differentiation theory and provide innovative diagnosis and treatment strategies for clinical CHF.

Paeoniflorin-free subfraction of Paeonia lactiflora Pall. shows the potential of anti-hepatic fibrosis: an integrated analysis of network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatic fibrosis is a major consequence of liver disease. Radix Paeoniae Rubra (RPR), the dry root of Paeonia lactiflora Pall., has a long history of clinical application in traditional Chinese medicine (TCM) for the treatment of liver diseases. The researches of RPR active ingredients are mainly focused on paeoniflorin. However, the functional roles of other ingredients have not been clarified sufficiently in the treatment of hepatic fibrosis with RPR. AIM OF THE STUDY: This study was to figure out the anti-hepatic fibrosis potential and mechanisms of CS-4, one of the paeoniflorin-free subfraction of RPR. MATERIALS AND METHODS: With the guide of bioassay, CS-4, a subfraction of RPR showed in vitro inhibition of hepatic stellate cell activation, was obtained using multiple chromatographic techniques. Its ingredients were determined by UPLC-Q-TOF-MS/MS. Then, the target profiles of ingredients were obtained from the HERB database, and the disease targets were collected from the DisGeNET database. Through the network pharmacology method, a protein-protein interaction network of CS-4 against hepatic fibrosis was established to analyze and excavate the potential therapeutic targets. Combined with the KEGG analysis, a series of signaling pathways were obtained, thereby validated by western blot analysis. RESULTS: The paeoniflorin-free subfraction of RPR, CS-4, was obtained and showed the most potential anti-fibrotic effect in vitro. A total of 20 main ingredients were identified from CS-4 and considered as its active ingredients. From HERB and DisGeNET databases, 1460 potential targets of CS-4 and 1180 disease targets were obtained, respectively. The overlapped 79 targets were considered to exert the potential anti-fibrosis effect of CS-4, such as JAK2, MYC, SMAD3, and IFNG. The gene enrichment analysis revealed that classical TGF-ß/Smad signaling pathway and nonclassical TGF-ß/PI3K-AKT signaling pathway may be two of the main mechanisms of CS-4 against hepatic fibrosis, which supported by western blot analysis. CONCLUSION: In this study, a paeoniflorin-free subfraction with potential anti-hepatic fibrosis activity in vitro, CS-4, was obtained from RPR. Its multiple ingredients, multiple targets, and multiple mechanisms against hepatic fibrosis were explained by network pharmacology and verified by western blot analysis to further support the clinical applications of RPR.

[Progress of target determination and mechanism of bioactive components of traditional Chinese medicine].

The pharmacodynamic substances of traditional Chinese medicine(TCM) are the basis for the research of TCM and the development of innovative drugs. However, the lack of clarity of targets and molecular mechanisms is the bottleneck problem that restricts the research of pharmacodynamic substances of TCM. Bioactive components are the material basis of the efficacy of TCM, which exert activity by regulating the corresponding targets. Therefore, it is very important to identify the targets of the bioactive components to elucidate the pharmacological mechanism of TCM. Proteins are the most important drug targets, and study of the interaction between the proteins and bioactive components of TCM plays a key role in the development of pharmacological mechanism of TCM. In recent years, the main techniques for detecting the interaction between the bioactive components and proteins include surface plasmon resonance, fluorescence resonance energy transfer, bio-layer interference, molecular docking, proteome chip, target fishing, target mutant, and protein crystallization techniques, etc. This review summarized the biological target detection techniques and their applications in locating the targets of the bioactive components in TCM in the last decade, and this paper will provide useful strategies to elucidate the pharmacological mechanisms of TCM.

[Trace therapeutic substances of traditional Chinese medicine: great resources of innovative drugs derived from traditional Chinese medicine].

The traditional Chinese medicine(TCM) contains very complex constituents. Besides the major constituents, there are a large number of unclear trace constituents with novel skeletons and potent bioactivities, which have been regarded as one of the important therapeutic substances and the great resources of innovative drugs derived from TCM. The present review highlighted that the development of the trace therapeutic substances of TCM is closely depends on the advanced technologies for their identification, isolation, structure elucidation, and bioactivity evaluation. Additionally, this paper reviewed the novel trace compounds derived from Chinese herbal medicines which have been published in Organic Letters during 2001-2021, and summarized the important licensed drugs originated from the trace therapeutic substances and the discovery and development of trace therapeutic substances of 8 kinds of Chinese herbal medicines. This review provides references for the research and development of TCM therapeutic substances and innovative drugs.

Multiple anti-non-alcoholic steatohepatitis (NASH) efficacies of isopropylidenyl anemosapogenin via farnesoid X receptor activation and TFEB-mediated autophagy.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) can develop into cirrhosis, liver failure, or hepatocellular carcinoma without effective treatment. However, there are currently no drugs for NASH treatment, and the development of new therapeutics has remained a major challenge in NASH research. Advances in traditional Chinese medicine to treat liver disease inspired us to search for new NASH candidates from Chi-Shao, a widely used traditional Chinese medicine. PURPOSE: In this research, we aimed to clarify the anti-NASH effect and the underlying mechanism of isopropylidenyl anemosapogenin (IA, 1), which was a new lead compound isolated from Chi-Shao. STUDY DESIGN AND METHODS: Isopropylidenyl anemosapogenin (IA, 1) was first discovered by collagen type I α 1 promoter luciferase bioassay-guided isolation and then characterized by single crystal X-ray diffraction analysis and enriched by semi-synthesis. Using various molecular biology techniques, the multiple anti-NASH efficacies and mechanisms of IA were clarified based on in vitro LX-2 and Huh7 cell models, along with the in vivo choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced mouse model and bile duct ligation (BDL)-induced rat model. The UPLC-MS/MS method was used to assess the plasma concentration of IA. RESULTS: A new lead compound IA was isolated from the traditional Chinese medicine Chi-Shao, which showed significant anti-liver fibrosis activity in TGF-ß1-treated LX-2 cells and anti-liver steatosis activity in oleic acid-treated Huh7 cells. Furthermore, IA could significantly ameliorate in vivo CDAHFD-induced liver injury by activating the farnesoid X receptor pathway, including its targets Nr0b2, Abcb11, and Slc10a2. Simultaneously, IA activated the autophagy pathway by activating the TFEB factor, thereby promoting lipid degradation. Its liver-protective and anti-fibrosis activities were verified by the BDL-induced rat model. Finally, with an oral administration of 100 mg/kg, IA achieved the maximum plasma concentration of 1.23 ± 0.18 µg/ml at 2.67 ± 0.58 h. CONCLUSION: IA, an unreported lupine-type triterpenoid isolated from Chi-shao, can significantly alleviate liver injury and fibrosis via farnesoid X receptor activation and TFEB-mediated autophagy, which indicates that IA could serve as a novel therapeutic candidate against NASH.

Bioactive neolignans and lignans from the roots of Paeonia lactiflora.

Two new neolignans and one new lignan (1-3) were obtained from the roots of Paeonia lactiflora. Their structures were unambiguously elucidated based on extensive spectroscopic analysis, single-crystal X-ray crystallography, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 was a racemic mixture and successfully resolved into the anticipated enantiomers via chiral-phase HPLC. Compound 3 demonstrated moderate inhibitory activity against human carboxylesterase 2A1 (hCES2A1) with an IC50 value of 7.28 ± 0.94 µmol·-1.

Bioactive sesquineolignans from the twigs of Litsea cubeba.

In a continuing search for biological natural products with structure diversity from traditional Chinese herbs, five new sesquineolignans (1-5) were isolated from an ethyl acetate extract of the twigs of Litsea cubeba. Their structures were elucidated based on MS, 1D and 2D NMR spectroscopic data, as well as experimental electronic circular dichroism (ECD) spectra. Compounds 1-5 showed moderate inhibitory effects against LPS-induced NO production in RAW264.7 macrophages, with IC50 values of 16.2, 20.2, 22.1, 15.1, and 16.6 µmol·L-1, respectively.

[A new phenolic acid ester from solid culture of Colletotrichum capsici, an endophytic fungus from Paeonia lactiflora].

A new phenolic acid ester, 4'-hydroxyphenylethyl 4,8(R)-dihydroxyphenylpropionate(1), was isolated from an endophytic fungus Colletotrichum capsici of Paeonia lactiflora roots, along with eight known phenolic derivatives, tyrosol(2), 2-(4-hydroxyphenyl) ethyl acetate(3), methyl p-hydroxyphenylacetate(4), methyl m-hydroxyphenylacetate(5), 4-(4-hydroxyphene-thoxy)-4-oxobutanoic acid(6), 4-hydroxyphenethyl methyl succinate(7), trichodenol B(8) and 4-hydroxyphenethyl 2-(4-hydroxyphenyl) acetate(9). Their structures were identified by a combination of high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) spectroscopy, ultraviolet(UV) spectroscopy and electronic circular dichroism(ECD) spectroscopy. Compounds 2-9 were isolated from this fungus for the first time.

Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate.

Macrophages play a critical role in innate and adaptive immunity, and the regulation of macrophage function in inflammatory disease treatment has been widely studied. Litsea cubeba is an important Chinese medicinal plant used for the treatment of inflammatory diseases. However, the inflammatory bioactive ingredients in L. cubeba and underlying molecular mechanisms are poorly understood. Herein, we first obtained and elucidated a novel isoquinoline alkaloid, Litcubanine A (LA), from L. cubeba. An in vitro study indicated that LA could significantly inhibit LPS-induced activation of inflammatory macrophages via the NF-κB pathway, leading to the decrease of inflammatory factors including iNOS, TNF-α, and IL-1ß. Moreover, LA showed an inhibiting effect on the expression of NO in macrophages by directly binding to iNOS protein. Molecular simulation docking also demonstrated that active LA created an interaction with GLU 371 residue of iNOS via attractive charge derived from the N→O group, revealing its highly selective inhibition toward iNOS. By using the IκK inhibitor and iNOS inhibitor, these two regulatory targets of LA on inflammatory macrophages were verified in vitro. Finally, by using a caudal fin resection model in zebrafish larvae, and the skin wound healing model in mice, we proved in vivo that LA down-regulated the secretion of local inflammatory factors by inhibiting macrophage recruitment and activation at the early stage of the injury. Collectively, our study demonstrated that the novel isoquinoline alkaloid LA suppresses LPS-induced activation of inflammatory macrophages by modulating the NF-κB pathway, suggesting that inflammatory macrophage activation pathway is an effective target for inflammation treatment, and LA is a new pharmacophore for the development of novel and effective anti-inflammatory agents to regulate local macrophages.

The effect of an isoquinoline alkaloid on treatment of periodontitis by regulating the neutrophils chemotaxis.

Neutrophil plays a critical role in the progression of periodontitis. In general, its chemotaxis and activation are benefit for the host defense of bacterial infection and inflammation. However, previous studies have reported that the hyperactive and reactive neutrophils appear to be one of the reasons for tissue destruction in periodontitis tissues. In this study, we investigated an isoquinoline alkaloid Litcubanine A (LA), which from the Traditional Chinese medicinal plant, Litsea cubeba. We found LA showed significant activity in inhibiting neutrophils chemotaxis in the zebrafish yolk sac microinjection model in vivo and in mouse neutrophils in vitro. Further investigation proved that LA could inhibit the expression levels of neutrophil respiratory burst-related and inflammation-related genes CYBB and NCF2, as well as inhibit the activation of MAPK signaling pathway. Moreover, using LA, we successfully achieved the effect of reducing periodontitis bone loss by regulating neutrophil chemotaxis and related functions in a mouse ligature-induced periodontitis model.

Effect of Selenium and Peroxynitrite on Immune Function of Immature Dendritic Cells in Humans.

BACKGROUND Selenium and peroxynitrite are known to support the growth and activity of immune cells, including T cells, B cells and macrophages. However, the role of these factors in the immune function of human immature dendritic cells (imDCs) is not clear. MATERIAL AND METHODS Monocytes from a mixture of blood samples were isolated using Ficoll density gradient centrifugation and purified with immunomagnetic beads before being induced into imDCs. Cells then either received no treatment (control group), or treatment with sodium selenite (Na2SeO3, Se), 3-morpholinosydnonimine (SIN1, which decomposes into peroxynitrite), or Se+SIN1. Cell viability, migration, and antiphagocytic abilities, oxidative stress, and protein expression of extracellular signal-regulated kinases (ERK) and MMP2 were assessed using a CCK8 assay, cell counter and flow cytometry, microplate spectrophotometer, and Western blot analysis, respectively. RESULTS Viability of imDCs was unaffected by 0.1 µmol/L of Na2SeO3, although 1 mmol/L of SIN1 decreased it significantly (P<0.05). Chemotactic migration and antiphagocytic abilities were inhibited and enhanced, respectively, by treatment with Na2SeO3 and SIN1 (P<0.05). Activities of superoxide dismutase and glutathione peroxidase were increased by Na2SeO3 and Se+SIN1 (P<0.001). Glutathione content decreased with exposure to Na2SeO3 and SIN1 (P<0.05), but increased after treatment with Se+SIN1 (P<0.05). Levels of reactive oxygen species only increased with SIN1 treatment (P<0.05). Treatment with Na2SeO3, SIN1 and Se+SIN1 increased ERK phosphorylation and decreased MMP2 protein expression (P<0.05). CONCLUSIONS Selenium and peroxynitrite can influence immune function in imDCs by regulating levels of reactive oxygen species or glutathione to activate ERK and promote antigen phagocytosis, as well as by decreasing MMP2 expression to inhibit chemotactic migration.

Selenium Regulation of the Immune Function of Dendritic Cells in Mice Through the ERK, Akt and RhoA/ROCK Pathways.

Selenium levels can regulate the function of T cells, macrophages, B cells, natural killer cells and other immune cells. However, the effect of selenium on the immune function of dendritic cells (DCs) isolated from selenium-supplemented mice is unknown. In this study, C57BL/6J mice were randomly divided into three groups and fed diets containing low (0.08 ppm), medium (0.25 ppm) or high (1 ppm) selenium levels for 8 weeks. Immature (imDCs) and mature (mDCs) dendritic cells were then isolated from the bone marrow. Next, the migration, phagocytic capacity and mixed lymphocyte reaction (MLR) for imDCs and mDCs were detected by transwell and flow cytometry. The levels of C-C chemokine receptor type 7 (CCR7), major histocompatibility complex II (MHCII) and reactive oxygen species (ROS) were assayed by flow cytometry. F-actin and superoxide dismutase (SOD) activity was detected by fluorescence microscopy and SOD assay kit, respectively. In addition, the extracellular signal-regulated kinase (ERK), Akt, Ras homolog gene family member A/Rho-associated protein kinase (RhoA/ROCK) signalling, selenoprotein K (SELENOK) and glutathione peroxidase 1 (GPX1) levels were measured by western blot analysis. The results indicated that selenium deficiency enhanced the migration of imDCs by ROS and SELENOK-mediated ERK, Akt and RhoA/ROCK pathways but impaired the antigen uptake of imDCs. Although a high selenium level inhibited the migration of imDCs, it had no effect on phagocytic capacity. For mDCs, low selenium levels impaired free migration, and high levels inhibited the chemotactic migration involved in F-actin and CCR7, respectively. Low and high selenium levels impaired the MLR by inhibiting MHCII surface localisation, which might be related to ROS- and SELENOK-mediated ERK, Akt and RhoA/ROCK signalling pathways. In summary, selenium may regulate the immune function of mouse DCs through the ROS- and SELENOK-mediated ERK, Akt and RhoA/ROCK signalling.

[A new lignan glucoside from root of Paeonia lactiflora].

A new lignan glucoside,(+)-fragransin A_2-4-O-ß-D-glucopyranoside(1), has been isolated from the dry root of Paeonia lactiflora by column chromatography on silica gel, Sephadex LH-20, and MCI-gel resin, as well as preparative RP-HPLC. The structure of the new compound was elucidated by spectroscopic data analysis(MS, UV, IR, CD, 1 D and 2 D NMR) and chemical method. Compound 1 showed moderate inhibition against lipopolysaccharide induced nitric oxide production in RAW264.7 macrophages, with an IC_(50) value of 21.3 µmol·L~(-1).

[Effect of Siegesbeckiae Herba in treating chronic pain].

The treatment of pain with complementary and alternative medicine has gradually attracted international attention. Traditional Chinese medicine(TCM) with clear composition and mechanism will become a new starting point for new drug research and development. Siegesbeckiae Herba is a commonly used TCM herb in the treatment of rheumatic arthralgia. With a clear chemical composition, Siegesbeckiae Herba has a long history of clinical application and a certain modern research basis in the treatment of chronic pain. It has good research and development prospects in the treatment of analgesia. Based on the occurrence principle of pain and the known mechanism of action of Siegesbeckiae Herba, we discussed the advance of studies on Siegesbeckiae Herba in three aspects, namely inflammatory pain, neuropathic pain and cancer pain, so as to provide reference for further basic research and development and application of new TCM.

Community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus in a Chinese adult: A case report.

RATIONALE: Methicillin-resistant Staphylococcus aureus (MRSA) has been established as an important cause of severe community-acquired pneumonia (CAP) with very high mortality. Panton-Valentine leukocidin (PVL) producing MRSA has been reported to be associated with necrotizing pneumonia and worse outcome. The incidence of community-acquired MRSA (CA-MRSA) pneumonia is very low, as only a few CA-MRSA pneumonia cases were reported in the last few years. We present a case of severe CAP caused by PVL-positive MRSA with ensuing septic shock. PATIENT CONCERNS: A 68-year-old male with no concerning medical history had developed a fever that reached 39.0°C, a productive cough that was sustained for 5 days, and hypodynamia. He was treated with azithromycin and alexipyretic in a nearby clinic for 2 days in which the symptoms were alleviated. However, 1 day later, the symptoms worsened, and he was taken to a local Chinese medicine hospital for traditional medicine treatment. However, his clinical condition deteriorated rapidly, and he then developed dyspnea and hemoptysis. DIAGNOSIS: CA-MRSA pneumonia and septic shock. The sputum culture showed MRSA. Polymerase chain reaction of MRSA isolates was positive for PVL genes. INTERVENTIONS: Mechanical ventilation, fluid resuscitation, and antibiotic therapy were performed. Antibiotic therapy included mezlocillin sodium/sulbactam sodium, linezolid, and oseltamivir. OUTCOMES: He died after 12 hours of treatment. LESSONS: This is a report of severe pneumonia due to PVL-positive CA-MRSA in a healthy adult. CA-MRSA should be considered a pathogen of severe CAP, especially when combined with septic shock in previously healthy individuals.

[Research progress of natural alkaloids with analgesic activity].

Pain is a protective defense response of the body to harmful stimuli. Long-term pain not only seriously affects the body of the patient and brings great pain to the patient, but also brings huge economic burden to the patient's family and society. It has become one of the most serious problems affecting human health. At present, opioids and non-steroidal anti-inflammatory drugs(NSAIDs) are commonly used as painkillers, but they tend to cause a variety of adverse reactions or risk of addiction. To find and develop new analgesic drugs, which are safer and more effective, has become the hot spot and difficulty in medical research. A variety of alkaloids derived from terrestrial plants, microorganisms, marine organisms and fungi have been an important source of clinical analgesic medicines. Various alkaloids have been proved to have good analgesic effects, such as morphine and the related to opioids, the main analgesic active components from Corydalis Rhizoma and Aconiti Lateralis Radix Praeparata. Here we summarized the research progress of natural alkaloids with analgesic activity, in order to provide reference for the research and development of analgesic drugs based on natural products.