Objective To design and synthesize PROTAC degraders targeting the SARS-CoV-2 main protease （M^pro）based on PROTAC technology. Methods Compound 3w was used as the M^pro ligand, and the indole N atom in the solvent-exposed region was selected as the linker attachment site. A series of M^pro PROTACs were designed and synthesized by conjugating compound 3w with the CRBN ligand pomalidomide through alkane linkers of different lengths. The structures of the target compounds were confirmed by ¹H NMR, ¹³C NMR, and HRMS. Western Blot analysis was employed to evaluate their degradation activity and explore its mechanism in M^pro-HEK-293T cells. Results Four novel M^pro PROTACs（A1-A4）were successfully synthesized. The most potent compound A4 demonstrated M^pro degradation activity with a DC₅₀ value of 5.2 μmol/L, and its degradation mechanism was validated. Conclusion A novel class of M^pro PROTAC degraders were successfully designed and synthesized, and their protein degradation capability and mechanism of action were demonstrated. These results provided lead compounds for the research and development of antiviral degraders against SARS-CoV-2.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

This study aims to identify the main chemical compounds, investigate the effects of different drying methods on the quality, and determine the appropriate drying method of Callicarpae Nudiflorae Folium. UPLC-UV-Q-TOF-MS was employed to characterize and identify 35 main compounds, including phenylethanoid glycosides, flavonoids, and iridoids in Callicarpae Nudiflorae Folium. A method for the simultaneous determination of 8 compounds with strong UV absorption and high content was established to evaluate the quality of Callicarpae Nudiflorae Folium dried by different methods. UPLC-UV-Q-TOF-MS combined with principal component analysis(PCA) was employed to compare the Callicarpae Nudiflorae Folium samples treated by microwave drying at different power(119, 231, and 385 W), drying in the shade, sun drying, and oven drying at different temperatures(50, 60, 70, 80, 90, and 100 ℃). The total content of decaffeoyl acteoside, picroside Ⅲ, galuteolin, forsythin B, acteoside, isoacteoside, 6-hydroxyluteolin-7-glucoside, and caffeic acid in Callicarpae Nudiflorae Folium, as well as the content of most compounds, decreased with the rise in drying temperature and with the decrease in microwave power. Considering the content of compounds, low carbon, and energy saving, microwave drying at 231 W, low-temperature drying, or natural drying is recommended for the production of Callicarpae Nudiflorae Folium. This study provides a scientific basis for the selection of drying methods for Callicarpae Nudiflorae Folium at the place of origin and for the improvement of quality standards.
Desiccation/methods* ; Drugs, Chinese Herbal/chemistry* ; Callicarpa/chemistry* ; Plant Leaves/chemistry* ; Chromatography, High Pressure Liquid ; Flavonoids/analysis* ; Microwaves ; Mass Spectrometry

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.
Humans ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B/drug therapy* ; Hepatitis B virus ; Antiviral Agents/therapeutic use* ; Gastroenterology

Objectives: To examine the short-term and mid-term effects of surgical treatment of obstructive hypertrophic cardiomyopathy (HCM) in one center. Methods: The perioperative data and short-term follow-up outcomes of 421 patients with obstructive HCM who received surgical treatment at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University from January 2017 to December 2021 were analyzed retrospectively. There were 207 males and 214 females, aged (56.5±11.7) years (range: 19 to 78 years). Preoperative New York Heart Association (NYHA) classification included 45 cases of class Ⅱ, 328 cases in class Ⅲ, and 48 cases in class Ⅳ. Fifty-eight patients were diagnosed with latent obstructive HCM and 257 patients had moderate or more mitral regurgitation with 56 patients suffering from intrinsic mitral valve diseases. All procedures were completed by a multidisciplinary team, including professional echocardiologists involving in preoperative planning for proper mitral valve management strategies and intraoperative monitoring. A total of 338 patients underwent septal myectomy alone, and 59 patients underwent mitral valve surgery along with myectomy. A single transaortic approach was used in 355 patients, and a right atrial-atrial septal/atrial sulcus approach was used in 51 other patients. Long-handled minimally invasive surgical instruments were used for the procedures. Student t test, Wilcoxon rank sum test, χ² test or Fisher exact test were used to compare the data before and after surgery. Results: The aortic cross-clamping time of septal myectomy alone was (34.3±8.5) minutes (range: 21 to 94 minutes). Eighteen patients had intraoperative adverse events and underwent immediate reoperation, including residual obstruction (10 patients), left ventricular free wall rupture (4 patients), ventricular septal perforation (3 patients), and aortic valve perforation (1 patient). Four patients died during hospitalization, and 11 patients developed complete atrioventricular block requiring permanent pacemaker implantation. After discharge, 384 (92.1%) patients received a follow-up visit with a median duration of 9 months. All follow-up patients survived with significantly improved NYHA classifications: 216 patients in class Ⅰ and 168 patients in class Ⅱ (χ²=662.73, P<0.01 as compared to baseline). At 6 months after surgery, follow-up echocardiography showed that the thickness of the ventricular septum ((13.6±2.5) mm vs. (18.2±3.0) mm, t=23.51, P<0.01) and the peak left ventricular outflow tract gradient ((12.0±6.3) mmHg vs. (93.4±19.8) mmHg, 1 mmHg=0.133 kPa, t=78.29, P<0.01) were both significantly lower than baseline values. Conclusion: The construction of the surgical team (including echocardiography experts), proper mitral valve management strategies, identification and management of sub-mitral-valve abnormalities, and application of long-handled minimally invasive surgical instruments are important for the successful implementation of septal myectomy with satisfactory short-and medium-term outcomes.
Male ; Female ; Humans ; Retrospective Studies ; Atrial Fibrillation ; Treatment Outcome ; Cardiomyopathy, Hypertrophic/surgery* ; Mitral Valve Insufficiency/surgery* ; Ventricular Septum

Complicated chemical reactions occur in the decoction of traditional Chinese medicines(TCMs) which features complex components, influencing the safety, efficacy, and quality controllability of TCMs. Therefore, it is particularly important to clarify the chemical reaction mechanism of TCMs in the decoction. This study summarized eight typical chemical reactions in the decoction of TCMs, such as substitution reaction, redox reaction, isomerization/stereoselective reaction, complexation, and supramolecular reaction. With the "toxicity attenuation and efficiency enhancement" of aconitines and other examples, this study reviewed the reactions in decoction of TCMs, which was expected to clarify the variation mechanisms of key chemical components in this process and to help guide medicine preparation and safe and rational use of medicine in clinical settings. The current main research methods for chemical reaction mechanisms of decoction of TCMs were also summed up and compared. The novel real-time analysis device of decoction system for TCMs was found to be efficient and simple without the pre-treatment of samples. This device provides a promising solution, which has great potential in quantity evaluation and control of TCMs. Moreover, it is expected to become a foundational and exemplary research tool, which can advance the research in this field.
Medicine ; Medicine, Chinese Traditional ; Research Design

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

The end of the COVID-19 infection peak in 2022 prompts a backlog of cardiovascular surgical patients to gradually return to the hospital, resulting in a surge in cardiovascular surgeries. However, against the backdrop of the COVID-19 pandemic, the clinical practice of cardiovascular surgery faces many problems. Therefore, organized by Beijing Anzhen Hospital, experts in cardiovascular surgery and related fields have formulated hospital expert experience on perioperative treatment principles of cardiovascular surgery for patients infected with COVID-19. This article summarizes the clinical decision-making of patients requiring cardiovascular surgery after COVID-19 infection, and advises on the corresponding recommendations according to the existing evidence-based medical evidence as well as the actual clinical practice experience of relevant experts. The main content of the article includes special requirements for cardiovascular surgical treatment indications in patients with COVID-19 infection, selection of surgical timing, special requirements of preoperative, intraoperative and postoperative management, etc., which aims to provide COVID-19-infected patients with guidance on rational decision-making when receiving cardiovascular surgery.

Quality is the guarantee for the clinical safety and effectiveness of Chinese medicine. Accurate quality evaluation is the key to the standardization and modernization of Chinese medicine. Efforts have been made in improving Chinese medicine quality and strengthening the quality and safety supervision in China, but rapid and accurate quality evaluation of complex Chinese medicine samples is still a challenge. On the basis of the development of ambient mass spectrometry and the application in quality evaluation of complex Chinese medicine systems in recent years, the authors developed the multi-scenario Chinese medicine quality evaluation strategies. A systematic methodology was proposed in specific areas such as real-time monitoring of the quality of complex Chinese medicine decoction system, rapid toxicity grading of compound Chinese patent medicine, and evaluation of bulk medicinals of Chinese patent medicine. Allowing multi-scenario analysis of Chinese medicine, it is expected to provide universal research ideas and technical methods for rapid and accurate quality evaluation of Chinese medicine and boost the high-quality development of Chinese medicine industry.
China ; Drugs, Chinese Herbal ; Mass Spectrometry ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Reference Standards

Through the combing of ancient books of Chinese herbal medicine in the past dynasties， a textual research of Coptidis Rhizoma involved the name， origin， medicinal parts， producing area， quality evaluation， harvesting and processing methods in famous classical formulas was conducted in this paper. After textual research， the mainstream varieties of Coptidis Rhizoma in the Ranunculaceae family before Tang and Song dynasties were Coptis chinensis and C. chinensis var. brevisepala， after the Ming and Qing dynasties， C. deltoidea， C. teeta and C. omeiensis were gradually praised. In ancient times， the authentic producing area of Coptidis Rhizoma has the characteristics of gradually moving to the west. The eastern Coptidis Rhizoma was highly praised in the early stage， while in the later stage， western Coptidis Rhizoma like chicken feet was highly praised. In the early stage， western Coptidis Rhizoma probably originated from C. chinensis and its genus， while Coptidis Rhizoma like chicken feet was cultivated， and no wild species has been found so far. As Coptidis Rhizoma has mixed use of multiple origins in ancient books of past dynasties， based on the current shortage of market resources in C. teeta and C. deltoidea， there are also endangered and protected plants of C. chinensis var. brevisepala and C. omeiensis， combined with the mainstream medicines and resources of past generations， it is recommended to choose C. chinensis as the base of the formulas. In ancient times， there were many processing methods for Coptidis Rhizoma， such as frying and wine-， ginger-， honey-processed. In the process of developing famous classical formulas， the appropriate processing specifications of Coptidis Rhizoma should be selected based on the original source records and the requirements of the medicinal material.