OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

The telomere structure in the cell nucleus is crucial for maintaining the stability and functions of chromosomes.Telomerase is a ribonucleoprotein reverse transcriptase,which catalyzes the elongation of telomeres using its own RNA as a template,thereby counteracting the shortening of telomeres caused by chromosome replication and cell division.Due to its overexpression in over 85％of malignant tumor cells,telomerase has emerged as a highly promising biomarker and a novel target for cancer therapy.In recent years,given the importance of precise quantification of telomerase activity in guiding medical diagnosis and treatment strategies,researchers have developed various high-performance telomerase detection techniques.Among these,electrochemical biosensing technique has cause much attention due to its high sensitivity,operational convenience,rapid response,and ease of miniaturization.This paper focused on the latest advances in electrochemical sensing technique for detection of telomerase activity,aiming to provide inspiration for designing novel telomerase activity detection strategies by elucidating three unique properties of telomerase primer extension products.

Objective To investigate the risk factors for pneumonia complicating infectious mononucleosis(IM)in adults and construct a nomogram prediction model.Methods A retrospective analysis was conducted on 198 IM patients admitted to the Second Affiliated Hospital of Air Force Medical University from January 2015 to December 2021.Patients were divided into pneumonia group(n=52)and non-pneumonia group(n=146)based on whether pulmonary infection occurred during hospitalization.The baseline data(age,gender,place of onset,etc.),clinical manifestations(maximum body temperature,lymph node enlargement,splenomegaly,etc.),and inflammatory indicators[white blood cell count(WBC),C-reactive protein(CRP),etc.]were compared between the two groups.Kaplan-Meier curves were plotted to analyze the key indicators affecting the hospital stay of IM patients.Multivariate logistic regression was used to analyze the independent risk factors for pneumonia complicating IM in adults and construct a nomogram prediction model based on the identified risk factors.The predictive efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve and the consistency of the model was assessed using the calibration curve.The fit of the model was evaluated using the Hosmer-Lemeshow test.Additionally,the sensitivity,specificity,and accuracy of the model were assessed using confusion matrix.Results Compared with non-pneumonia group,the pneumonia group had a significantly higher proportion of patients from rural areas,with body mass index(BMI)≥24 kg/m2,smoking history,hepatomegaly,fever duration of≥7 d,as well as increased total hospitalization costs and average daily hospitalization costs,and prolonged hospital stay(P<0.05).The proportion of patients with a history of antibiotic use was lower in the pneumonia group(P<0.05).Kaplan-Meier survival analysis showed that patients from rural areas,with BMI≥24 kg/m2,smoking history,no prophylactic use of antibiotics,fever duration≥7 d,and hepatomegaly had significantly prolonged hospital stays(P<0.05).Multivariate logistic regression analysis revealed that living in a rural area(OR=4.089,P<0.05),hepatomegaly(OR=4.082,P<0.05),and elevated WBC(OR=1.205,P<0.05)were independent risk factors for pneumonia complicating IM in adults,while the prophylactic use of antibiotics(OR=0.142,P<0.05)was an independent protective factor.The area under the ROC curve of the constructed nomogram prediction model was 0.827(95%CI 0.762-0.892),and the slope of the calibration curve was close to 1,and the Hosmer-Lemeshow test showed χ2=5.299,P=0.725,indicating good consistency and fit of the prediction model.The results of the confusion matrix assessment showed that the sensitivity of the model was 0.669(0.624-0.773),the specificity was 0.827(0.724-0.930),and the accuracy was 0.732(0.665-0.793).Conclusion The nomogram prediction model based on place of onset,hepatomegaly,the prophylactic use of antibiotics and WBC has excellent fit and discrimination,providing an effective quantitative tool for prognosis assessment of IM.

Objective To summarize the reasons and management strategies of reoperation after oblique lateral interbody fusion(OLIF),and put forward preventive measures.Methods From October 2015 to December 2019,23 patients who under-went reoperation after OLIF in four spine surgery centers were retrospectively analyzed.There were 9 males and 14 females with an average age of(61.89±8.80)years old ranging from 44 to 81 years old.The index diagnosis was degenerative lumbar intervertebral dics diseases in 3 cases,discogenie low back pain in 1 case,degenerative lumbar spondylolisthesis in 6 cases,lumbar spinal stenosis in 9 cases and degenerative lumbar spinal kyphoscoliosis in 4 cases.Sixteen patients were primarily treated with Stand-alone OLIF procedures and 7 cases were primarily treated with OLIF combined with posterior pedicle screw fixation.There were 17 cases of single fusion segment,2 of 2 fusion segments,4 of 3 fusion segments.All the cases underwent reoperation within 3 months after the initial surgery.The strategies of reoperation included supplementary posterior pedicle screw instrumentation in 16 cases;posterior laminectomy,cage adjustment and neurolysis in 2 cases,arthroplasty and neuroly-sis under endoscope in 1 case,posterior laminectomy and neurolysis in 1 case,pedicle screw adjustment in 1 case,exploration and decompression under percutaneous endoscopic in 1 case,interbody fusion cage and pedicle screw revision in 1 case.Visu-al analogue scale(VAS)and Oswestry disability index(ODI)index were used to evaluate and compare the recovery of low back pain and lumbar function before reoperation and at the last follow-up.During the follow-up process,the phenomenon of fusion cage settlement or re-displacement,as well as the condition of intervertebral fusion,were observed.The changes in in-tervertebral space height before the first operation,after the first operation,before the second operation,3 to 5 days after the second operation,6 months after the second operation,and at the latest follow-up were measured and compared.Results There was no skin necrosis and infection.All patients were followed up from 12 to 48 months with an average of(28.1±7.3)months.Nerve root injury symptoms were relieved within 3 to 6 months.No cage transverse shifting and no dislodgement,loosening or breakage of the instrumentation was observed in any patient during the follow-up period.Though the intervertebral disc height was obviously increased at the first postoperative,there was a rapid loss in the early stage,and still partially lost after reopera-tion.The VAS for back pain recovered from(6.20±1.69)points preoperatively to(1.60±0.71)points postoperatively(P＜0.05).The ODI recovered from(40.60±7.01)％preoperatively to(9.14±2.66)％postoperatively(P＜0.05).Conclusion There is a risk of reoperation due to failure after OLIF surgery.The reasons for reoperation include preoperative bone loss or osteoporosis the initial surgery was performed by Stand-alone,intraoperative endplate injury,significant subsidence of the fusion cage after surgery,postoperative fusion cage displacement,nerve damage,etc.As long as it is discovered in a timely manner and handled properly,further surgery after OLIF surgery can achieve better clinical results,but prevention still needs to be strengthened.

OBJECTIVE: To explore characteristics, management strategies and preventive measures of fusion device displacement after oblique lateral interbody fusion (OLIF) in treating lumbar lesions. METHODS: The clinical data of 12 patients with fusion device displacement after OLIF for lumbar lesions in 4 medical centers from October 2014 to December 2018 were retrospectively analyzed, including 4 males and 8 females, aged from 53 to 81 years old;2 patients with lumbar disc degeneration, 4 patients with lumbar spinal stenosis, 3 patients with lumbar degenerative spondylolisthesis and 3 patients with lumbar degenerative kyphosis;preoperative dual-energy X-ray bone mineral density (BMD) was detected in 1 patient with T-value > -1 SD, 5 patients with T-value >-1~-2.5 SD, and 6 patients with T-value <-2.5 SD;9 patients with single-segment fusion, 1 patient with 2-segment fusion, and 2 patients with 3-segment fusion;standalone OLIF was performed in 9 patients and OLIF combined with posterior pedicle screws in 3 patients. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate low back pain and lumbar function recovery at the time of fusion graft displacement and at the latest follow-up, respectively. In addition, according to imaging results during follow-up, the fusion device subsidence or redisplacement, loosening or fracture of internal fixation, and interbody fusion were observed, and the changes in the height of interbody space on the segment with fusion device displacement were measured and compared. RESULTS: There were no necrosis or infection in skin incision of 10 patients after reoperation, and 12 patients were followed up for 12 to 48 months. VAS for low back pain decreased from 3 to 8 points at the time of fusion device displacement to 0 to 2 points at the latest follow-up. ODI recovered from 31% to 51% at the time of fusion transfer to 5% to 13% at the latest follow-up. There was no loosening or fracture of the pedicle screw system during follow-up. All 11 patients with bone grafting with fusion apparatus had fusion apparatus subsidence and no further displacement of fusion apparatus. The vertebral space height recovered from 9.0 to 12.7 mm at the time of fusion graft displacement to 8.0 to 11.8 mm at the latest follow-up. Interbody fusion was obtained in all patients except 1 with no imaging results at the latest follow-up. CONCLUSION OLIF could be used for fusion of lumbar lesions, and there is a risk of fusion organ displacement after operation, especially in cases of bone loss or osteoporosis before surgery, end-plate injury during surgery, and Stand-alone mode, and most of them occur within 3 months after operation. Surgery is required for the transposition of the fusion apparatus in the Stand-alone OLIF mode during the primary operation. Although good clinical results could be obtained by timely detection and accurate treatment, it is still necessary to emphasize the precise selection of cases before operation, the appropriate application of OLIF, and precise operation during operation to prevent displacement of fusion device.
Humans ; Spinal Fusion/instrumentation* ; Female ; Male ; Middle Aged ; Aged ; Aged, 80 and over ; Lumbar Vertebrae/surgery* ; Retrospective Studies ; Pedicle Screws

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα⁺) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα⁺ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒ 29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

Objective: This study aimed to investigate whether cytokine profiles and virological markers might add value in monitoring the effects of peginterferon (PEG-IFN) therapy for hepatitis B e-antigen (HBeAg) positive chronic hepatitis B (CHB). Methods: HBeAg positive patients with CHB were treated with PEG-IFN for 48 weeks. Clinical biochemical, and HBV serological indexes, as well as cytokines, were detected at baseline and every 12 weeks. Results: A total of 116 patients with CHB were enrolled in this study; 100 patients completed the 48-week treatment and follow-up, of whom 38 achieved serum HBeAg disappearance, 25 achieved HBeAg seroconversion, 37 showed HBsAg decreases ≥ 1 log ₁₀ IU/mL, 9 showed HBsAg disappearance, and 8 became HBsAb positive. The cytokine levels at baseline and during treatment were similar between the HBeAg disappearance group and non-disappearance group. The disappearance of HBeAg was independently associated with HBeAg levels at weeks 12 and 24, and with the HBeAg decline at week 24 ( P < 0.05). The HBsAg response was independently associated with HBsAg, the HBsAg decline, HBeAg, the HBeAg decline at week 12, and HBsAg at week 24 ( P< 0.05). Conclusion There was no significant correlation between the response to interferon (IFN) and cytokines during PEG-IFN treatment. The changes in virological markers predicted the response to IFN after 48 weeks.
Biomarkers ; Cytokines ; DNA, Viral ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; Hepatitis B, Chronic/drug therapy* ; Humans ; Interferon-alpha/therapeutic use* ; Polyethylene Glycols/therapeutic use*

The ethyl acetate part of the alcoholic extract of Cordia dichotoma fruits was purified by a combination of normal-phase silica gel column chromatography, Sephadex LH-20 gel column chromatography and semi-preparative HPLC, and the structure was identified by modern spectroscopic techniques (UV, IR, MS, NMR). A total of 10 compounds were isolated and identified as cordilide (1), (S)-2-hydroxy-3-(4′-hydroxyphenyl) propanoic acid (2), vanillic acid (3), p-coumaric acid (4), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-1-one (5), benzoic acid (6), p-hydroxypropiophenone (7), p-hydroxyacetophenone (8), 5′-methoxyevofolin B (9) and vanillin (10). Among them, compound 1 is a pair of new phenylpropanoid enantiomers, and compounds 3, 6, 8 and 9 were isolated for the first time from the genus.

Exosomes are lipid bilayer membranous vesicles actively secreted by various cells in the organism， which are like nanoparticles and have messenger targeting. Combining with the theory of supramolecular "Qi chromatography" of traditional Chinese medicine （TCM）， research ideas and strategies of modernization of TCM can be constructed. Exosomes are secreted by cells， and the membrane contains nucleic acids， proteins， lipids and small molecular metabolites and others， which can accurately coordinate the functions of each cell， concentrate and transmit the functional information of the parent cell， and is the concise form of reflecting cell functions. At the same time， it is loaded with the "imprinted templates" of the supramolecular "Qi chromatography" theory of TCM. If the "imprinted templates" carrying rules among the gene-protein-lipid-small molecules wrapped in it is studied， the modern experimental research ideas and strategies of TCM theory can be established for revealing the functions of the body's meridians and viscera. Firstly， the present situation of exosomes， including discovery， secretion， characteristics， functions， attribution， uptake， research methods and application status， were reviewed in this paper. And the natural properties of its precise messenger targeted delivery vehicle were elaborated， reflecting the operation law of microscopic substances in meridians and viscera. Secondly， to explore it as an important carrier of the concentrated "imprinted templates" of the supramolecular "Qi chromatography" theory of TCM， and integrating the research methods of exosomes and supramolecular chemistry of TCM， this paper proposes experimental research ideas and strategies on the microscopic material basis of meridians and viscera， compatibility of TCM compound， and targeting of TCM targeted preparations.

In the era of artificial intelligence based on big data， data acquisition， storage and processing are more convenient， which provides a guarantee for accelerating the development of traditional Chinese medicine （TCM）， but it has not yet achieved organic integration with TCM theory. Based on preliminary research on the supramolecular "Qi chromatography" theory of TCM， combined with the current development trend of artificial intelligence， this paper analyzed the biological intelligence attribute of the function of TCM supramolecular "imprinting template"， in order to provide reference for the development of TCM drug innovation. Both the human body and Chinese materia medica are giant complex supramolecular bodies evolved from natural organisms. According to the "imprinting template"， the "social molecules" are controlled step by step to form the meridians and viscera. The interaction produces the original theory of TCM， in which the self-recognition， self-assembly， self-organization and self-replication of the "imprinting template" reflect the "intelligence" function attributes：the human body uses the "imprinting template" to self-identify and sense the ingredients of TCM， and store the memory information database in the meridian and collateral organs in the form of "imprinting template"， and then pass the "imprinting template". The comparison， analysis， and judgment of imprinting templates guide the self-assembly， self-organization and self-replication among "molecular society"， synthesize biological machines， produce biological functions， repair or strengthen biological supramolecular bodies， and present the most basic "intelligence" attribute. This suggests that the theory of theory-method-prescription-medicine of TCM is the weak embodiment of biological "intelligence"， while the human brain function is the strong embodiment of biological "intelligence". Since the intelligent function of supramolecular "imprinting template" runs through the natural world， artificial intelligence that can characterize the strong "intelligence" form of the human brain will also be integrated into all aspects of the natural world， suggesting the development direction of "intelligence" functionalization of drug innovation mode.