OBJECTIVE: To identify the underlying molecular mechanism of Modified Hu-Lu-Ba-Wan (MHW) in alleviating renal lesions in mice with diabetic kidney disease (DKD). METHODS: The db/db mice were divided into model group and MHW group according to a random number table, while db/m mice were settled as the control group (n=8 per group). The control and model groups were gavaged daily with distilled water [10 mL/(kg·d)], and the MHW group was treated with MHW [17.8 g/(kg·d)] for 6 weeks. After MHW administration for 6 weeks, indicators associated with glucolipid metabolism and urinary albumin were tested. Podocytes were observed by transmission electron microscopy. Kidney transcriptomics was performed after confirming therapeutic effects of MHW on DKD mice. The relevant target of MHW' effect in DKD was further determined by enzyme-linked immunosorbent assay, Western blot analysis, immunohistochemistry, and immunofluorescence staining. RESULTS: Compared with the model group, MHW improved glucose and lipid metabolism (P<0.05), and reduced lipid deposition in the kidney. Meanwhile, MHW reduced the excretion of urinary albumin (P<0.05) and ameliorated renal damage. Transcriptomic analysis revealed that the inflammation response, particularly the interleukin-17 (IL-17) signaling pathway, may be responsible for the effect of MHW on DKD. Furtherly, our results found that MHW inhibited IL-17A and alleviated early fibrosis in the diabetic kidney. CONCLUSION MHW ameliorated renal damage in DKD via inhibiting IL-17A, suggesting a potential strategy for DKD therapy.
Animals ; Diabetic Nephropathies/genetics* ; Interleukin-17/antagonists & inhibitors* ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Kidney/ultrastructure* ; Podocytes/metabolism* ; Mice ; Albuminuria ; Lipid Metabolism/drug effects* ; Mice, Inbred C57BL

The development of anticancer drugs to treat triple-negative breast cancer (TNBC) is an ongoing challenge. Immunogenic cell death (ICD) has garnered considerable interest worldwide as a promising synergistic modality for cancer chemoimmunotherapy. However, only few drugs or treatment modalities can trigger an ICD response and none of them exert a considerable clinical effect against TNBC. Therefore, new agents with potentially effective chemoimmunotherapeutic response are required. In this study, five new cyclometalated Ir(III) complexes containing isoquinoline alkaloid CˆN ligands were designed and synthesized. Among them, Ir-1 exhibited the highest in vitro cytotoxicity. Mechanistically, Ir-1 could trigger autophagy-dependent ferroptosis and a subsequent ferroptosis-dependent ICD response as well as indoleamine 2,3-dioxygenase (IDO) inhibition via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in MDA-MB-231 cells. When immunocompetent BALB/c mice were vaccinated with Ir-1-treated dying TNBC cells, antitumor CD8⁺ T-cell response and Foxp3⁺ T-cell depletion were induced, resulting in long-lasting antitumor immunity in TNBC cells. Moreover, combination therapy with Ir-1 and anti-PD1 could substantially augment in vivo therapeutic effects. Based on these results, Ir-1 is a promising candidate for chemoimmunotherapy against TNBC and its effects are mediated synergistically via ICD induction and IDO blockage.

Objective To perform structural analysis on the homogeneous polysaccharide SP800301 isolated from Saposhnikoviae Radix to determine its chemical structure.Methods Polysaccharides were separated and purified from Saposhnikoviae Radix using column chromatography,such as DEAE-cellulose and Sephadex G-75.The molecular weight distribution,monosaccharide composition,oligosaccharide fragments,sugar residue types,and glycosidic bond connection of the isolated homogeneous polysaccharide SP800301 from Saposhnikoviae Radix were analyzed using electrospray ionization multistage mass spectrometry,gas chromatography-mass spectrometry,and nuclear magnetic resonance to determine its structure.The appearance characteristics of the Saposhnikoviae Radix polysaccharide were characterized using electron and atomic force microscopy.Results Polysaccharide SP800301 extracted from Saposhnikoviae Radix had good homogeneity with a molecular weight of 9.1×104 g/mol.The uronic acid content was 52.72%.The monosaccharide group comprised rhamnose,galacturonic acid,glucose,galactose,and arabinose,with a molar ratio of 4.3:58.1:25.4:5.0:7.3.The polysaccharide was mainly composed of polygalacturonic acid as the primary chain.The branched chain was comprised of rhamnose,galacturonic acid,galactose,glucose,and arabinose,with arabinose at the end of the branched chain and part of the galacturonic acid in the sugar chain forming a methyl ester.Conclusion This study clarified the chemical structure of the homogeneous polysaccharide SP800301 from Saposhnikoviae Radix,enriched the chemical composition of Saposhnikoviae Radix polysaccharides,laid the foundation for further research on the immune regulatory mechanism of Saposhnikoviae Radix polysaccharides,and provided a scientific basis for clinically using Saposhnikoviae Radix.

Objective:To study the effect of a modified behavioral treatment(MBT)on functional anejaculation and analyze the factors influencing the therapeutic efficacy.Methods:We enrolled in this study 59 men aged 24-45 years visiting the Andrology Clinic of Shanghai First Maternity and Infant Hospital from August 2019 to May 2021 and complaining of aejaculation in sexual inter-course but normally ejaculating during masturbation.Thirty-nine of the patients underwent conventional behavioral treatment(the CBT group)and the other 20 received MBT,namely,changing the masturbation method combined with audiovisual stimulation during sexual intercourse(the MBT group).We compared the therapeutic effects between the two groups of patients,and analyzed the correlation of the outcomes of MBT with age,abstinence duration,use of audiovisual stimulation,change of the sexual position,mean bilateral testis volume and sex hormone levels.Results:After treatment,22(37.29％)of the patients achieved successful ejaculation at least once in sexual intercourse,11(55.00％)in the MBT group,and the other 11(28.21)in the CBT group,with a significantly higher effec-tiveness rate in the former than in the latter(P＜0.05).The effectiveness rate was significantly correlated to the method of standing-position masturbation plus sexual intercourse and reduction in the frequency of masturbation among various strategies of behavioral treat-ment(P＜0.05).Conclusion:MBT has a certain effect on functional anejaculation,and targeting the previous events of the patient is the key to the therapeutic efficacy.Further exploration of more effective strategies of behavioral treatment will become the trend of de-velopment in the management of functional anejaculation.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the K_D of which reached to 8.722×10^-10 g·mL^-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.

  Objective  To understand the current status of surgical treatment for hemophilia osteoarthropathy (HO) in China.  Methods  Using an online questionnaire, select domestic hospitals that partici-pated in the compilation of the 'Guideline for perioperative management of hemophilia patients undergoing orthopaedic surgery in China ', in addition to members of the National Joint Surgery Group, and the Orthopedic Branch of the Chinese Medical Association for targeted investigation and analysis.  Results  A total of 17 domestic hospitals were included, all of which were general hospitals. Hospitals that started HO surgery treatment before 2000 accounted for 35.29%. A total of 3057 surgical cases of HO were reported by those hospitals. The most commonly performed surgical procedures were hip and knee joint replacement. The most commonly used coagulation factor replacement regimen was recombinant coagulation factor preparation. Ten hospitals reported finding patients with transfusion-related infectious diseases. Bleeding and hematoma formation were the most frequently reported surgical complications. Excessive length of hospital stay and high economic costs were the most frequently reported problems.  Conclusions  Surgical treatment for HO in 17 hospitals is mainly carried out in some large comprehensive medical centers in the eastern region. Compared with the patient base, the popularity and number of surgeries are still relatively insufficient. It is necessary to further standardize the treatment system by standardizing factor replacement and strengthening rehabilitation to improve surgical treatment outcomes.

The dental operative microscope has been widely employed in the field of dentistry, particularly in endodontics and operative dentistry, resulting in significant advancements in the effectiveness of root canal therapy, endodontic surgery, and dental restoration. However, the improper use of this microscope continues to be common in clinical settings, primarily due to operators' insufficient understanding and proficiency in both the features and established operating procedures of this equipment. In October 2019, Professor Jingping Liang, Vice Chairman of the Society of Cariology and Endodontology, Chinese Stomatological Association, organized a consensus meeting with Chinese experts in endodontics and operative dentistry. The objective of this meeting was to establish a standard operation procedure for the dental operative microscope. Subsequently, a consensus was reached and officially issued. Over the span of about four years, the content of this consensus has been further developed and improved through practical experience.
Humans ; Dentistry, Operative ; Consensus ; Endodontics ; Root Canal Therapy ; Dental Care

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

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.