ObjectiveTo investigate the urate-lowering effect of Shenling Qushi prescription in the mouse model of hyperuricaemia. MethodsSixty-three C57BL/6N mice were randomly assigned to the following groups （n=9）： Control， model， low-dose （6 g·kg^-1） Shenling Qushi prescription， medium-dose （12 g·kg^-1） Shenling Qushi prescription， high-dose （24 g·kg^-1） Shenling Qushi prescription， medium-dose Shenling Qushi prescription plus febuxostat （12+0.003 g·kg^-1）， and febuxostat （3 mg·kg^-1）. A mouse model of persistent hyperuricaemia was established via intraperitoneal injection of potassium oxazolamide （250 mg·kg^-1） combined with oral administration of allopurinol （300 mg·kg^-1） over a 28-day period. Concurrently， the prescription was administered orally at the specified doses once daily for 21 consecutive days. Throughout the experiment， mouse body weight， food intake， water consumption， and urine output were measured and recorded. Kidney and liver indices were calculated. Renal histopathological changes were observed by haematoxylin and eosin staining. Serum uric acid （SUA） and urinary uric acid （UUA） levels， along with xanthine oxidase （XOD） and adenosine deaminase （ADA）， alanine aminotransferase （ALT） and aspartate aminotransferase （AST） activities， were determined. Real-time PCR was employed to assess the mRNA levels of urate anion transporter 1 （URAT1） and glucose transporter 9 （GLUT9） in the renal tissue， alongside those of XOD and ADA in the liver tissue. The protein levels of URAT1 and GLUT9 in the renal tissue were determined by Western blot. ResultsCompared with the normal group， model mice exhibited reduced food intake and body weight （P<0.01）， decreased water consumption yet increased urine output， no significant change in the liver index but increased kidney index （P<0.01）. Pathological findings revealed renal tissue damage including glomerular atrophy， epithelial cell detachment， and inflammatory cell infiltration. Furthermore， the model group exhibited elevated UUA and SUA levels （P<0.01）， enhanced activities of ALT， AST， XOD， and ADA in the liver tissue （P<0.05， P<0.01）， upregulated mRNA and protein levels of URAT1 and GLUT9 in the renal tissue （P<0.05）， alongside markedly elevated mRNA levels of XOD and ADA in the liver （P<0.01）. Compared with the model group， the Shenling Qushi prescription groups showed no significant changes in body weight or food intake， with water consumption and urine output remaining within normal ranges， alleviated glomerular atrophy， with reduced pathological damage such as inflammatory infiltration， declined UUA and SUA levels （P<0.01）， and increased activities of ALT， AST， XOD， and ADA in the serum （P<0.01）. Real-time PCR results demonstrated that Shenling Qushi prescription downregulated the mRNA levels of URAT1 and GLUT9 in the renal tissue （P<0.05， P<0.01） and XOD and ADA in the hepatic tissue （P<0.05， P<0.01）. Western blot results demonstrated Shenling Qushi prescription reduced the protein levels of URAT1 and GLUT9 （P<0.05， P<0.01）. ConclusionShenling Qushi prescription modulates fluid balance and reduces uric acid levels， thereby alleviating renal injury in hyperuricaemic mice. This effect is highly likely mediated through inhibition of uric acid synthesis and reabsorption.

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Objective:To understand the current status and characteristics of clinical trials for oral diseases in China, for the purpose of providing a reference for the research and development of oral diseases in China.Methods:Retrieving the information on clinical trials related to oral diseases registered on the "Platforms for drug clinical trial registration and information" of the National Medical Products Administration from the date of the database establishment to December 31, 2024. The number of clinical trials, type of drugs, trial phases, indication, trial scope, design types were statistically analyzed.Results:As of December 31, 2024, a total of 578 drug clinical trials for oral disease were registered, accounting for 2.1% (578/27 905) of the clinical trials disclosed on the platform during the same period. Bioequivalence clinical trials accounted for the highest proportion [73.9% (427/578)], followed by Phase Ⅰ [9.0% (52/578)], Phase Ⅱ [8.0% (46/578)], and Phase Ⅲ [4.5% (26/578)]. The 578 clinical trials involved 149 types of trial drugs, mainly chemical drugs, among which 127 were developed by domestic pharmaceutical enterprises and 27 by international pharmaceutical enterprises (the five investigational drugs have undergone clinical trials by both domestic and international pharmaceutical companies). The project leader units of the 578 drug clinical trials were distributed in 27 provinces, autonomous regions, municipalities, and Hong Kong Special Administrative Region. Excluding 427 bioequivalence clinical trials, the project leader units of 151 new drug clinical trials showed a significant aggregation phenomenon, and only three specialized oral hospitals have served as project leader units for drug clinical trials.Conclusions:The number of drug clinical trials for oral disease in China has generally shown an increasing trend, but there are still problems such as small number of clinical trials, low proportion of investment in new drug development and international multicenter trials, concentrated indications of clinical trials and insufficient clinical trial experience in specialized oral medical institutions. Enhancing the enthusiasm and innovation capabilities of domestic pharmaceutical enterprises in the research and development of oral diseases drugs, exploring the advantages of traditional Chinese medicine/natural medicine resources for oral diseases, and establishing a clinical research system in specialized oral medical institutions are of great significance for the development of oral drugs.

Objective:To analyze the current status of clinical trials of Chinese materia medica for the purpose of registration in China; To provide reference for the research and development of new TCM drugs.Methods:Clinical trials of Chinese materia medica/natural medicine registered in Drug Clinical Trial Registration and Information Disclosure Platform were retrieved from inception to December 31, 2024. Excel 2019 software was used to input and analyze the data such as the number of registered clinical trials, date of first publication, study status, field of indication, trial phases, sponsors, group leader, and design types.Results:A total of 1 137 Chinese materia medica clinical trials had been registered, accounting for 4.12% of the total number registered on the platform. Phase Ⅱ clinical trials accounted for the highest proportion (58.8%), and 99.7% of clinical trials conducted domestically. The sponsors were predominantly domestically pharmaceutical enterprises. These 1 137 clinical trials of Chinese materia medica clinical trials involved 752 drug categories, 28 dosage forms, and 796 varieties (the same class of drugs had different drug dosage forms), with capsules being the most common. The indications primarily focused on respiratory, digestive, cardio-cerebrovascular, neuropsychiatric, gynecological diseases. The group leader of clinical trials was distributed in 28 provinces, among which the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine as the group leader, undertook the most clinical trials of TCM. 89.9% of the clinical trials adopted the randomized controlled trial design, and only 31.9% of the clinical trials purchased insurance for the subjects.Conclusion:The research and development of new TCM drugs has entered a phase of vigorous development. Further efforts are still needed in establishing systematic guidelines for Chinese materia medica clinical trials, accelerating the internationalization of TCM, exploring innovative dosage forms and indications, and strengthening the protection of participants' rights.

Objective:To review drug clinical trial development in Shaanxi province and to understand the effectiveness of the implementation of a record system in promoting drug clinical trial development.Methods:Based on the data of drug clinical trials in Shaanxi province released on the official website of the National Medical Products Administration, this study made a statistical analysis of the number of drug clinical trial institutions, regional distribution, registered majors and principal investigators, and the development of drug clinical trial projects.Results:After implementing drug clinical trial institution registration, the drug clinical trial institutions in Shaanxi Province developed rapidly, increasing from 20 in the qualification period to 46, with a growth rate of 130%. A total of 113 specialties were recorded, of which the highest number of professional records were for endocrinology and oncology. 46 institutions recorded 1, 094 principal investigators and participated in 3803 drug clinical trial projects. However, only 8 institutions had undertaken drug clinical trial projects as group leaders.Conclusions:The number of drug clinical trial institutions in Shaanxi province increased significantly, reflecting a good overall development status. However, issues still exist, such as unbalanced development of clinical trial resources within the region, insufficient researchers with the ability to conduct clinical trials, relatively concentrated drug clinical trial projects, and lack of experience in undertaking clinical trials as a group leader.

Objective:To understand the current status and characteristics of clinical trials for oral diseases in China, for the purpose of providing a reference for the research and development of oral diseases in China.Methods:Retrieving the information on clinical trials related to oral diseases registered on the "Platforms for drug clinical trial registration and information" of the National Medical Products Administration from the date of the database establishment to December 31, 2024. The number of clinical trials, type of drugs, trial phases, indication, trial scope, design types were statistically analyzed.Results:As of December 31, 2024, a total of 578 drug clinical trials for oral disease were registered, accounting for 2.1% (578/27 905) of the clinical trials disclosed on the platform during the same period. Bioequivalence clinical trials accounted for the highest proportion [73.9% (427/578)], followed by Phase Ⅰ [9.0% (52/578)], Phase Ⅱ [8.0% (46/578)], and Phase Ⅲ [4.5% (26/578)]. The 578 clinical trials involved 149 types of trial drugs, mainly chemical drugs, among which 127 were developed by domestic pharmaceutical enterprises and 27 by international pharmaceutical enterprises (the five investigational drugs have undergone clinical trials by both domestic and international pharmaceutical companies). The project leader units of the 578 drug clinical trials were distributed in 27 provinces, autonomous regions, municipalities, and Hong Kong Special Administrative Region. Excluding 427 bioequivalence clinical trials, the project leader units of 151 new drug clinical trials showed a significant aggregation phenomenon, and only three specialized oral hospitals have served as project leader units for drug clinical trials.Conclusions:The number of drug clinical trials for oral disease in China has generally shown an increasing trend, but there are still problems such as small number of clinical trials, low proportion of investment in new drug development and international multicenter trials, concentrated indications of clinical trials and insufficient clinical trial experience in specialized oral medical institutions. Enhancing the enthusiasm and innovation capabilities of domestic pharmaceutical enterprises in the research and development of oral diseases drugs, exploring the advantages of traditional Chinese medicine/natural medicine resources for oral diseases, and establishing a clinical research system in specialized oral medical institutions are of great significance for the development of oral drugs.

Objective:To review drug clinical trial development in Shaanxi province and to understand the effectiveness of the implementation of a record system in promoting drug clinical trial development.Methods:Based on the data of drug clinical trials in Shaanxi province released on the official website of the National Medical Products Administration, this study made a statistical analysis of the number of drug clinical trial institutions, regional distribution, registered majors and principal investigators, and the development of drug clinical trial projects.Results:After implementing drug clinical trial institution registration, the drug clinical trial institutions in Shaanxi Province developed rapidly, increasing from 20 in the qualification period to 46, with a growth rate of 130%. A total of 113 specialties were recorded, of which the highest number of professional records were for endocrinology and oncology. 46 institutions recorded 1, 094 principal investigators and participated in 3803 drug clinical trial projects. However, only 8 institutions had undertaken drug clinical trial projects as group leaders.Conclusions:The number of drug clinical trial institutions in Shaanxi province increased significantly, reflecting a good overall development status. However, issues still exist, such as unbalanced development of clinical trial resources within the region, insufficient researchers with the ability to conduct clinical trials, relatively concentrated drug clinical trial projects, and lack of experience in undertaking clinical trials as a group leader.

ObjectiveTo explore the therapeutic effect of Huangliansan on atopic dermatitis （AD） model mice induced by 2， 4-dinitrochlorobenzene （DNCB）. MethodA total of 42 male BALB/c mice were randomly divided into normal group， model group， hydrocortisone group， low， medium， and high-dose groups （0.3， 0.6， 1.2 g·kg^-1） of Huangliansan oil， and water extract group （0.6 g·kg^-1） of Huangliansan. In addition to the normal group， DNCB was applied on the back of mice in other groups to establish the AD model. On the 15^th day after DNCB stimulation， each group was given the corresponding drug or solvent， and the changes in skin lesions， dermatitis score， and frequency of scratching were observed and recorded. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the skin and spleen. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA levels of filaggrin （FLG）， lorophane （LOR）， and involucrin （IVL） in skin， as well as immunoglobulin E （lgE）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and interferon-γ （IFN-γ） in spleen. ResultCompared with the normal group， the model group showed symptoms of skin swelling and scab， and the score of dermatitis， the frequency of scratching， and the spleen index were increased （P<0.05）. The expression levels of FLG， LOR， and IVL in skin tissue were significantly decreased （P<0.01）， and the mRNA expressions of IgE， IL-4， IL-6， IL-1β， and TNF-α in the spleen were significantly increased， while the expression level of IFN-γ was significantly decreased （P<0.01）. Compared with the model group， the symptoms of skin erythema， scaly， and scab of mice in each drug group were alleviated to varying degrees， and the score of dermatitis， the frequency of scratching， and the spleen index were decreased （P<0.05， P<0.01）. In addition， the expression levels of FLG， LOR， and IVL in the skin of mice in the drug group were increased （P<0.05， P<0.01）， and the mRNA expression of IgE， IL-4， IL-6， IL-1β， and TNF-α in spleen were decreased. IFN-γ was increased （P<0.05， P<0.01）， and the lesions of the skin and spleen were improved to varying degrees. The medium-dose group of Huangliansan oil and hydrocortisone group had the most obvious manifestations （P<0.05， P<0.01）. The indexes in the medium-dose group of Huangliansan oil were better than those in the water extract group of Huangliansan. ConclusionHuangliansan may improve the expression level of skin barrier protein， inhibit the expression of helper T cell 2 （Th2）-related inflammatory factors， increase the expression of helper T cell 1 （Th1） inflammatory factors， restore the skin barrier function and Th1/Th2 balance in the spleen， regulate the inflammatory response in the spleen of AD mice， and thus relieve AD. Huangliansan oil is more effective than water extract.

Objective:To investigate the efficacy and safety of dual wavelength pulsed dye laser combined with 30% supramolecular salicylic acid in the treatment of moderate and severe facial acne.Methods:Sixty patients with moderate and severe acne that visited the Dermatology Department of the First Affiliated Hospital of Chongqing Medical University from May 2020 to January 2021, were selected and randomly divided into observation group and control group, with 30 patients in each group. The observation group was given dual-wavelength pulsed dye laser combined with 30% supramolecular salicylic acid. 30% supramolecular salicylic acid was used once every two weeks, for a total of six times. Dual-wavelength pulsed dye laser was given once a month, for a total of three times. The control group was only given dual-wavelength pulsed dye laser, once a month, a total of three times.Results:Twenty-two cases (73.33%) in the observation group were effective, while 14 cases (46.67%) in the control group were effective. The efficacy of the observation group was better than that of the control group, and the difference was statistically significant (χ 2=4.44, P<0.05). There were no obvious adverse reactions in both groups. Conclusions:Dual-wavelength pulsed dye laser combined with 30% supramolecular salicylic acid is effective and safe in the treatment of moderate and severe facial acne, which is worth popularizing.

Objective:To investigate the clinical manifestation, pathological types, treatment and prognosis of primary tracheobronchial tumors in children.Methods:We retrospectively studied the primary tracheobronchial tumors patients who diagnosed from May 2009 to Jan 2021 in Guangzhou Women and Children Medical Center. The clinical manifestations, pathological types, therapeutic methods and prognosis were analyzed.Results:There were 15 patients identified as the primary tracheobronchial tumors, including synovial sarcoma (1 case), pulmonary inflammatory myofibroblastic tumor(IMT 4 cases), mucoepidermoid carcinoma(7 cases), infantile hemangioma (1 case), Ewing's sarcoma (1 case). Respiratory symptoms are the most complaint at the time of diagnosis including 15 patients with cough, 2 with hemoptysis, and 1 with dyspnea. Endoscopic treatment of tracheobronchial tumors was performed under extracorporeal membrane oxygenation (ECMO) support in 1 patient. Sleeve lobectomy was performed in 3 patients, lobectomies in 6, and local tumor resections in 4 patients including 2 patients suffered second surgery due to tumor recurrence.Conclusion:The clinical manifestations of the primary tracheobronchial tumors in children are nonspecific. Complete resection led to excellent outcome.