GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp. HK1-18 was studied by molecular network technique. Three linear tricyclic azaphilones, sequoiamonacins A-C (2a, 2b, 1), were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18, and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry. Guided by the mass spectra of sequoiamonacins A-C (2a, 2b, 1), the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18. By analyzing the MS/MS fragments of each parent ion in this cluster, 7 azaphilones (3-9) included 6 new ones (4-9) were predicted successfully. Then the MS/MS cracking regularity of this type of azaphilones was revealed. Compound 1 showed anti-inflammatory activity, which can inhibit the production of interleukin-1α (IL-1α) in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7, with an inhibitory rate of 29% at the concentration of 12.5 μg·mL^-1.

The World Health Organization has declared that the outbreak of coronavirus disease 2019(COVID-19) is a global pandemic. As mutations occurred in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the global epidemic still needs further concern. Worryingly, the effectiveness and neutralizing activity of existing antibodies and vaccines against SARS-CoV-2 variants is declining. There is an urgent need to find an effective antiviral medication with broad-spectrum inhibitory effects on novel coronavirus mutant strains against the SARS-CoV-2 infection. Neutralizing antibodies play an important role in the prevention and treatment of COVID-19. The interaction of spike-receptor-binding domain (Spike-RBD) of SARS-CoV-2 and human angiotensin-converting enzyme 2 (ACE2) is the first and critical step of SARS-CoV-2 infection. Hence, the SARS-CoV-2 Spike-RBD is a hot target for neutralizing antibodies development. Evusheld, the combination of Tixagevimab and Cilgavimab monoclonal antibodies (mAbs) targeting Spike-RBD exhibits neutralizing activity against BA.2.12.1, BA.4 and BA.5, which could be used as pre-exposure prophylaxis against SARS-CoV-2 infection. The nucleocapsid (N) protein is a conservative and high-abundance structural protein of SARS-CoV-2. The nCoV396 monoclonal antibody, isolated from the blood of convalescent COVID-19 patients against the N protein of SARS-CoV-2. This mAb not only showed neutralizing activity but also inhibits hyperactivation of complement and lung injury induced by N protein. The mAb 3E8 targeting ACE2 showed broadly neutralizing activity against SARS-CoV-2 and D614G, B.1.1.7, B.1.351, B.1.617.1 and P.1 variants in vitro and in vivo, but did not impact the biological activity of ACE2. Compared with neutralizing antibodies, small molecule inhibitors have several advantages, such as broad-spectrum inhibitory effect, low cost, and simple administration methods. Several small-molecule inhibitors disrupt viral binding by targeting the ACE2 and N-terminal domain (NTD) of SARS-CoV-2 spike protein. Known drugs such as chloroquine and hydroxychloroquine could also block the infection of SARS-CoV-2 by interacting with residue Lys353 in the peptidase domain of ACE2. The transmembrane protease serine 2 (TMPRSS2) inhibitors Camostat mesylate and Proxalutamide inhibit infection by blocking TMPRSS2 mediates viral membrane fusion. The main protease inhibitor Paxlovid and RNA-dependent RNA polymerase inhibitor Azvudine have been approved for treatment of COVID-19 patients. This review summarizes the current research status of neutralizing antibodies and small molecule inhibitors and prospects for their application. We expect to provide more valuable information for further studies in this field.

Objective To explore the common features of Chinese ethnic groups.Methods Eight body indexes of 62 ethnic groups in China were analyzed.Results The cluster analysis showed that 52 males and 59 females ethnic groups were grouped into the mixed group dominated by the northern ethnic group and the mixed group dominated by the southern ethnic group.Eight Han ethnic groups were grouped into each group,but no Han group was aggregated.The result of body index classification showed that the main body types of Chinese male population were long trunk,middle chest,wide shoulder,wide pelvis and middle leg.Middle body,wide chest,wide shoulder,wide pelvis and middle leg were the main body types of Chinese female population.This showed that the characteristics of Chinese ethnic groups had obvious consistency.The consistency of Chinese group features was related to its close origin.It should be said that Han nationality played an important role in the process of communication and integration of various ethnic groups in China.In the history of the Han nationality,there had been many large-scale population migration.The southern movement of the northern ethnic minorities into the northern Han and the southward movement of the northern Han into the south promoted the formation of the Southern Han,which made the southern Han and the northern Han had similar body features,and also promoted the southern ethnic minorities into the southern Han.In addition,the Han nationality who moved into minority areas also gradually integrated into minority areas.Conclusion There are obvious commonalities in Chinese ethnic groups.

Objective To explore the effectiveness and safety of percutaneous coronary artery shock wave balloon angioplasty(IVL)under the guidance of intravascular ultrasound(IVUS)for the treatment of severe calcification lesions in the left main artery(LM).Methods A total of 26 patients with severe LM(mouth,body,bifurcation)calcification admitted to Jiangnan University Affiliated Hospital from October 2022 to April 2024 were included,with an average age of 72.0(61.8,75.4)years.Under the guidance of IVUS,IVL was used for pre-treatment of calcified lesions,followed by percutaneous coronary intervention(PCI)with stent/drug balloon implantation.All patients were evaluated using IVUS before and after the use of IVL and after PCI.And compare the IVUS intracavity related data before and after treatment[plaque burden(PB)、minimum lumen area(MLA)、minimum lumen diameter(MLD)]and calcification fracture number,minimum stent area(MSA),stent expansion coefficient(expansion,EXP),etc.Results There were 26 patients(2 with opening lesions,7 with body lesions,and 17 with bifurcation lesions at the end of the main trunk),including 7 with stable angina pectoris(SAP),10 with unstable angina(UA),4 with acute ST-segment elevation myocardial infarction(STEMI),and 5 with non ST-segment elevation myocardial infarction(NSTEMI).The PB at the most severe site of calcification decreased by 79.50(76.00,83.75)％compared to 80.00(76.00,83.75)％after IVL(P=0.001),MLA increased by 3.39(3.14,3.68)mm2 compared to 3.38(3.14,3.67)mm2 after IVL(P=0.039),MLD increased by 3.21(3.07,3.30)mm compared to 3.20(3.07,3.30)mm after IVL(P=0.024),and there was 100％calcification rupture(1/2 cases,2/9 cases,≥3/15 cases).The stent/drug ball was successfully implanted 100％,with EXP of(89.15±4.42)％and an MSA of 7.20(6.46,7.45)mm2.No adverse events such as death,angina or recurrent myocardial infarction occurred during the 3 months follow-up after surgery.Conclusions After evaluation by IVUS and pre-treatment with IVL,PCI was successfully completed for severe calcification lesions in LM,and IVL can be used as an option for the treatment of severe calcification in LM.

Objective To analyze the risk factors and survival status of Epstein-Barr virus(EBV)infection in pa-tients with aplastic anemia(AA)after haploid allogeneic hematopoietic stem cell transplantation(Haplo-HSCT).Methods Clinical data of 78 AA patients who underwent Haplo-HSCT in the hematology department of a hospital from January 1,2019 to October 31,2022 were analyzed retrospectively.The occurrence and onset time of EBV viremia,EBV-related diseases(EBV diseases),and post-transplant lymphoproliferative disorders(PTLD)were ob-served,risk factors and survival status were analyzed.Results Among the 78 patients,38 were males and 40 were females,with a median age of 33(9-56)years old;53 patients experienced EBV reactivation,with a total inci-dence of 67.9％,and the median time for EBV reactivation was 33(13,416)days after transplantation.Among pa-tients with EBV reactivation,49 cases(62.8％)were simple EBV viremia,2 cases(2.6％)were possible EBV di-seases,and 2 cases(2.6％)were already confirmed EBV diseases(PTLD).Univariate analysis showed that age 1＜40 years old at the time of transplantation,umbilical cord blood infusion,occurrence of acute graft-versus-host disease(aGVHD)after transplantation,and concurrent cytomegalovirus(CMV)infection were independent risk fac-tors for EBV reactivation in AA patients after Haplo-HSCT.Multivariate analysis showed that concurrent CMV in-fection was an independent risk factor for EBV reactivation in A A patients after Haplo-HSCT(P=0.048).Ritu-ximab intervention before stem cell reinfusion was a factor affecting the duration of EBV reactivation(P＜0.05).The mortality of EBV viremia,EBV diseases,and PTLD alone were 8.2％,50.0％,and 100％,respectively.The 2-year overall survival rate of patients with and without EBV reactivation were 85.3％,and 90.7％,respectively,difference was not statistically significant(P=0.897).However,patients treated with rituximab had 2-year lower survival rate than those who did not use it,with a statistically significant difference(P=0.046).Conclusion EBV reactivation is one of the serious complications in AA patients after Haplo-HSCT,which affects the prognosis and survival of patients.

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×10⁹, 0.50×10⁹, 0.48×10⁹, 0.48×10⁹/L to 1.48×10⁹, 3.04×10⁹, 1.10×10⁹, 0.73×10⁹/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.
Humans ; Child ; Child, Preschool ; Adolescent ; Prospective Studies ; Glycogen Storage Disease Type I/drug therapy* ; Neutropenia ; Abdominal Pain ; Diarrhea/drug therapy* ; Hypoglycemia

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Based on the physiological and pathological characteristics of meridian sinew theory, the staging treatment of non-specific low back pain (NLBP) is explored to provide the reference of clinical practice. The twelve meridian sinews of the human body communicate with the bones and joints of the whole body, which governs the movement, body protection and defense, and meridian regulation. Physiologically, the meridian sinew maintains the functions of the lumbar region. In pathology, the meridian sinew may encounter stasis and pain, contraction and spasm or "transverse collateral" formation. According to the pathological staging of meridian sinew disorders, the progress of NLBP is divided into 3 phases and the corresponding treatments are provided. Mild stimulation and rapid analgesia is suggested to promote tissue repair at the early phase; muscle spasm is relieved to adjust muscular status at the middle phase; and the "cord-like" muscle foci is removed at the later phase of the disease.
Humans ; Low Back Pain ; Meridians ; Pain Management ; Analgesia ; Lumbosacral Region

In this study, ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and gas chromatography-mass spectrometry(GC-MS) were combined with non-targeted metabonomic analysis based on multivariate statistics analysis, and the content of five indicative components in nardosinone was determined and compared by UPLC. The main chemical components of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma were comprehensively analyzed. The results of multivariate statistical analysis based on liquid chromatography-mass spectrometry(LC-MS) and GC-MS were consistent. G1 and G2 of the imitative wild cultivation group and G8-G19 of the wild group were clustered into category 1, while G7 of the wild group and G3-G6 of the imitative wild cultivation group were clustered into category 2. After removing the outlier data of G1, G2, and G7, G3-G6 of the imitative wild cultivation group were clustered into one category, and G8-G19 of the wild group were clustered into the other category. Twenty-six chemical components were identified according to the positive and negative ion modes detected by LC-MS. The content of five indicative components(VIP>1.5) was determined using UPLC, revealing that chlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, linarin, nardosinone, and total content in the imitative wild cultivation group were 1.85, 1.52, 1.26, 0.90, 2.93, and 2.56 times those in the wild group, respectively. OPLS-DA based on GC-MS obtained 10 diffe-rential peaks. Among them, the relative content of α-humulene and aristolene in the imitative wild cultivation group were extremely significantly(P<0.01) and significantly(P<0.05) higher than that in the wild group, while the relative content of 7 components such as 5,6-epoxy-3-hydroxy-7-megastigmen-9-one, γ-eudesmol, and juniper camphor and 12-isopropyl-1,5,9-trimethyl-4,8,13-cyclotetrade-catriene-1,3-diol was extremely significantly(P<0.01) and significantly(P<0.05) lower than that in the wild group, respectively. Therefore, the main chemical components of the imitative wild cultivation group and wild group were basically the same. However, the content of non-volatile components in the imitative wild cultivation group was higher than that in the wild group, and the content of some volatile components was opposite. This study provides scientific data for the comprehensive evaluation of the quality of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma.
Gas Chromatography-Mass Spectrometry ; Chromatography, Liquid ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Tandem Mass Spectrometry

Phosphodiesterase 4 (PDE4) is an important member of the phosphodiesterase enzyme family that specifically catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP), activates the downstream phosphorylation cascade pathway by altering cAMP concentration, and is strongly associated with multiple diseases. Inhibition of PDE4 is clinically investigated as a therapeutic strategy in a broad range of disease areas, including respiratory system diseases, autoimmune disorders, central nervous system diseases, and dermatological conditions. However, the incidence of adverse reactions such as nausea and vomiting is relatively high in the marketed PDE4 inhibitors, which has stalled their clinical development. In this review, we provide an overview of the clinical progression and safety issues of the marketed PDE4 inhibitors. We also review the main causes underlying PDE4-mediated adverse effects by combining the structural analysis of the PDE4 protein, the mechanism of action of PDE4 inhibitors, and the related side effect mechanism research, aiming to provide a reference for the development of safe and effective PDE4 inhibitors.