The chemical constituents from Cephalotaxus lanceolata were isolated and purified by using multiple chromatographic techniques, including octadecylsilane(ODS), silica gel, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography(HPLC). A total of 17 compounds obtained were identified by using spectroscopic methods such as nuclear magnetic resonance(NMR), mass spectrometry(MS), and ultraviolet(UV) combined with literature data. Compound 1 was a new alkaloid dimer, named cephalancetine E. The known compounds were determined as cephalancetine A(2), 11-hydroxycephalotaxine(3), 4-hydroxycephalotaxine(4), cephalotaxine(5), epicephalotaxine(6), cephalotaxine β-N-oxide(7), acetylcephalotaxine(8), cephalotine A(9), cephalotine B(10), 11-hydroxycephalotaxine hemiketal(11), 3-deoxy-3,11-epoxy-cephalotaxine(12), cephalotaxinone(13), isocephalotaxinone(14), 2,11-epoxy-1,2-dihydro-8-oxo-cephalotaxine(15), cephalotaxamide(16), and drupacine(17), respectively. Compounds 11, 12, and 15 were isolated from the Cephalotaxus genus for the first time. The biological activity was tested for compounds 1-17. The results reveal that compound 17 displays potent inhibitory activities against three human cancer cell lines(HepG-2, MCF-7, and SH-SY5Y).
Cephalotaxus/chemistry* ; Humans ; Cell Line, Tumor ; Drugs, Chinese Herbal/pharmacology* ; Harringtonines/pharmacology* ; Molecular Structure ; Dimerization ; Alkaloids/isolation & purification* ; Magnetic Resonance Spectroscopy

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges.Conventional strategies always exhibit the insufficiencies in overall coverage,analytical efficiency,and degree of automation,and the results highly rely on the personal knowledge and experience.The goal of this work was to establish a software-aided approach,by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry(UHPLC/IM-QTOF-MS)and in-house high-definition MS2 library,to enhance the identification of prototypes and metabolites of the compound formulae in vivo,taking Sishen formula(SSF)as a template.Seven different MS2 acquisition methods were compared,which demonstrated the potency of a hybrid scan approach(namely high-definition data-independent/data-dependent acquisition(HDDIDDA))in the identification precision,MS1 coverage,and MS2 spectra quality.The HDDIDDA data for 55 reference compounds,four component drugs,and SSF,together with the rat bio-samples(e.g.,plasma,urine,feces,liver,and kidney),were acquired.Based on the UNIFI? platform(Waters),the efficient data processing workflows were estab-lished by combining mass defect filtering(MDF)-induced classification,diagnostic product ions(DPIs),and neutral loss filtering(NLF)-dominated structural confirmation.The high-definition MS2 spectral li-braries,dubbed in vitro-SSF and in vivo-SSF,were elaborated,enabling the efficient and automatic identification of SSF-associated xenobiotics in diverse rat bio-samples.Consequently,118 prototypes and 206 metabolites of SSF were identified,with the identification rate reaching 80.51％and 79.61％,respectively.The metabolic pathways mainly involved the oxidation,reduction,hydrolysis,sulfation,methylation,demethylation,acetylation,glucuronidation,and the combined reactions.Conclusively,the proposed strategy can drive the identification of compound formulae-related xenobiotics in vivo in an intelligent manner.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

Objective To investigate the protective effect of dandelion flavone(DF)on lipopolysaccharide(LPS)-induced colon epithelial cell injury by intervening oxidative stress and inflammation with AT-specific binding protein 2(SATB2).Methods Colon epithelial cells FHC were cultured.FHC cells were randomly divided into control group(normal cultured),LPS group(10 μg·mL-1 LPS),experimental-L group(10 μg·mL-1 LPS+1 μmol·L-1 DF),experimental-H group(10 μg·mL-1 LPS+5 μmol·L-1 DF),experimental-H+sh-NC group(transfected with sh-NC+10 μg·mL-1 LPS+5 μmol·mL-1 DF),experimental-H+sh-SATB2 group(transfected with sh-SATB2+10 μg·mL-1 LPS+5μmol·L-1 DF).The relative expression level of SATB2 protein in FHC cells was detected by Western blotting.The survival rate of FHC cells in each group was determined by tetramethylazolium blue(MTT).The apoptosis rate of FHC cells in each group was detected by flow cytometry.The levels of malondialdehyde(MDA)and interleukin-6(IL-6)in FHC cells were detected by the kit.Results The relative expression levels of SATB2 protein in control group,LPS group,experimental-H group,experimental-H+sh-NC group and experimental-H+sh-SATB2 group were 0.83±0.09,0.19±0.03,0.66±0.05,0.62±0.07 and 0.23±0.03,respectively;cell viability rates were(100.00±1.00)％,(48.16±4.31)％,(85.31±5.83)％,(81.39±6.47)％and(58.75±5.24)％,respectively;cell apoptosis rates were(3.27±0.81)％,(41.26±2.09)％,(11.35±1.04)％,(10.29±1.26)％and(35.87±2.15)％,respectively;MDA levels were(13.16±1.73),(52.87±3.49),(23.19±2.05),(20.98±3.17)and(44.87±3.05)μmol·L-1,respectively;IL-6 levels were(507.18±103.26),(2 132.09±198.15),(883.16±136.92),(801.69±119.85)and(1 736.29±206.91)pg·mL-1,respectively.The above indicators in the LPS group showed significant differences compared to the control group(all P＜0.05);the above indicators in the experimental-H group showed significant differences compared to the LPS group(all P＜0.05);the above indicators in the experimental-H+sh-SATB2 group showed significant differences compared to the experimental-H+sh-NC group(all P＜0.05).Conclusion DF has a protective effect on LPS-induced colon epithelial cell injury by intervening oxidative stress and inflammation through SATB2.

AIM To explore the laws in accumulation of dry matter and medicinal ingredients of Isatis indigotica Fort.in Longdong area,and determine the best harvest time to obtain the high-quality and high-yield medicinal plant.METHODS The I.indigotica had its agronomic traits investigated regularly;the accumulation laws of its uridine,guanosine,(R,S)-geichan and adenosine measured by HPLC;and its comprehensive utilization value in different periods evaluated by grey correlation method.RESULTS There existed significant variations among the plant height,plant width,leaf length,leaf width,number of leaves,leaf weight,root length,root diameter,root weight,and the yields of uridine,guanosine,(R,S)-goitrin and adenosine at different growth stages,whose peak values appeared in different period.Additionally,there were also obvious differences in the aforementioned indexes levels among different strains.The highest weighted correlation degree of the comprehensive utilization value of Longde and 2008-6-2 on October 9,and of 2008-11 and 2016-2 on October 24.On the whole,the 2008-6-2 and 2016-2 were superior to 2008-11 and Longde.CONCLUSION It is suggested that the best harvest time of I.indigotica in Longdong area is in mid to late October.

Objective:To compare the differences of clinical characteristics of temporal lobe epilepsy with bilateral hippocampal sclerosis (TLE-bHS) with those of temporal lobe epilepsy with unilateral hippocampal sclerosis (TLE-uHS).Methods:A retrospective analysis was performed. Forty-eight patients with confirmed TLE-bHS enrolled in Epilepsy Center, Department of Neurology, Second Affiliated Hospital, Medical School of Zhejiang University from January 2013 to January 2022 were chosen, and 101 patients with confirmed TLE-uHS admitted to our hospital at the same time period were selected as controls. Clinical data such as onset age, disease course, past medical history, seizure frequency, anti-seizure medications, video EEG and neuropsychological test results, and outcomes were analyzed.Results:Compared with the TLE-uHS group, the TLE-bHS group had higher male proportion, elder onset age, shorter disease course, higher seizure frequency, more types of past and currently used anti-seizure medications, lower proportion of autonomic nerve with aura, higher proportion of no aura at onset, higher proportion of slow head background movement in video EEG, and lower memory quotient, verbal memory scores and non-verbal memory scores, with significant differences ( P<0.05); the differences in ratio of past medical history and ratio of distributions of regions with interictal epileptiform abnormalities between the 2 groups were statistically significant ( P<0.05): the TLE-bHS group had significantly higher proportion of previous intracranial infection/encephalitis and higher ratio of bilateral temporal epileptiform abnormalities than the TLE-uHS group, while the TLE-uHS group had significantly higher proportion of patients with febrile convulsion history and higher ratio of unilateral temporal epileptiform abnormalities ( P<0.05). Only 10 patients (20.8%) in the TLE-bHS group received non-drug therapy, including anterior temporal lobectomy in 3 patients (Engel grading I in postoperative follow-up for 2 years), neuroregulatory therapy in 4, and ketogenic diet in 4; of the 55 patients (54.5%) in the TLE-uHS group who underwent anterior temporal lobectomy, 48 patients (87.3%) had Engel grading I, 1 patient (1.8%) had grading II, 4 (7.3%) had grading III, and 2 (3.6%) had grading IV after 2 years of follow-up. Conclusion:Differences in onset age, disease course, past medical history, seizure frequency, anti-seizure medications, and video EEG and neuropsychological test results can help to discriminate patients with TLE-bHS or with TLE-uHS.

Invasive fungal infections threaten the lives and health of humans, especially immunodeficient patients or hospitalized patients with serious underlying diseases, and impose a heavy economic burden on society. The emergence of drug-resistant fungi, the formation of biofilms, and the limits and side effects of existing antifungal drugs increase the difficulty of clinical treatment, and there is an urgent need for the development of novel antifungal drugs. Therefore, based on previous kinase chemical library antifungal activity screening studies, this paper further investigates the activity of anaplastic lymphoma kinase (ALK) inhibitor 3-[5-chloro-2-({2-methoxy-4-[4-(4-methylpiperazin-1-yl)hexahydropyridin-1-yl]phenyl}amino)pyrimidin-4-yl]-1H-indole (HG-14-10-04, HG) against various fungi and elucidates its mechanism of action. The in vitro antifungal activity of HG was evaluated by micro liquid-dilution method, time-killing curve, mycelium formation and biofilm formation assays. The results showed that HG exhibited inhibitory and even fungicidal effects against sensitive and resistant Candida albicans, Candida krusei, Cryptococcus neoformans, Candida tropicalis, Candida glabrata and Candida parapsilosis (MICs = 8-16 μg·mL^-1); HG significantly inhibited the mycelium and biofilm formation, and destroyed the mature biofilm; and it exhibited synergistic antifungal effects with amphotericin B. The antifungal mechanism of HG was investigated by flow cytometry and transmission electron microscopy, etc. Sequencing analysis showed a total of 1 041 differentially expressed genes, of which 666 were up-regulated and 375 were down-regulated. According to the GO functional classification results, the up-regulated genes were mainly involved in ribosome production, oxidation-reduction and other functions, while the down-regulated genes were mainly involved in the synthesis of carbohydrate, glycoproteins, glycolipids and their metabolism, GPI anchor synthesis, and cytoskeleton and other functions. In addition, HG could significantly increase the level of reactive oxygen species (ROS), induce the fungal necrosis, block the cell cycle at the G0/G1 phase, and change the ultrastructure of the fungi, especially the structure of the fungal cell wall. Therefore, the enhanced inhibitory and fungicidal activity of HG may be related to the elevation of ROS, alteration of cellular ultrastructure (especially cell wall structure) and cell cycle arrest at the G0/G1 phase. Further optimization of its structure will provide a basis for the discovery of novel antifungal drugs or lead compounds.