ObjectiveTo investigate the clinical efficacy and safety of iguratimod combined with the Chinese medicine Runzaoling in the treatment of primary Sjögren's syndrome （pSS）. MethodSeventy-two patients treated in the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine（TCM） from January 2021 to June 2022 who met the Western medical diagnosis of pSS and had the TCM syndrome of Yin deficiency and heat toxin syndrome were randomly assigned into an observation group and a control group， with 36 patients in each group. The observation group was treated with iguratimod combined with Runzaoling， and the control group was treated with iguratimod. The treatment in both groups lasted for 12 weeks. The clinical symptoms， EULAR Sjogren's syndrome patient reported index （ESSPRI）， EULAR Sjögren's syndrome disease activity index （ESSDAI）， erythrocyte sedimentation Rate （ESR）， C-reactive protein （CRP）， immunoglobulin （IgG）， Schirmer score， and saliva flow of the two groups were determined before and after treatment. Furthermore， the incidence of adverse reactions was compared between the two groups. ResultThe total response rate in the observation group was 75.0% （27 patients with response and 9 patients with no response）， which was higher than that （61.11%， 22 patients with response and 14 patients without response） in the control group （P<0.05）. After treatment， the ESSPRI， ESSDAI， and TCM syndrome scores in both groups decreased and the decreases were more obvious in the observation group than in the control group （P<0.05）. The treatment in both groups recovered the ESR， CRP， IgG， Schirmer score， and saliva flow （P<0.05）. Moreover， the observation outperformed the control group in terms of the ESR， CRP， IgG， and saliva flow （P<0.05） and had no significant difference in the Schirmer score compared with the control group. During the treatment period， 2 patients in the observation group had nausea， and 1 patient had an abnormal liver function， which were relieved after symptomatic treatment and did not affect the treatment. In the control group， 1 patient withdrew from the study due to rashes and showed no special discomfort in the follow-up 4 weeks， and 1 patient had nausea， which was relieved after symptomatic treatment. ConclusionIguratimod combined with Runzaoling has good clinical efficacy and safety in the treatment of pSS.

ObjectiveThis study aimed to observe the impact of sinomenine hydrochloride on the proliferation of fibroblasts and the mRNA expression of related genes in knee joint adhesion and contracture in rabbits. Additionally, we sought to explore its potential mechanisms in combating knee joint adhesion and contracture. MethodsFibroblasts were cultured in vitro, and experimental groups with varying concentrations of sinomenine hydrochloride were established alongside a control group. Cell proliferation was assessed using the CCK-8 assay. Changes in the mRNA expression of fibroblast-related genes following sinomenine hydrochloride treatment were evaluated using RT-qPCR. The impact of the drug on serum levels of inflammatory cytokines was determined using the ELISA method, and the expression of related proteins was assessed using Western blot. ResultsSinomenine hydrochloride was found to inhibit fibroblast viability, with viability decreasing as the concentration of sinomenine hydrochloride increased. The effects of sinomenine hydrochloride in all experimental groups were highly significant (P<0.05). At the mRNA expression level, compared to the control group, sinomenine hydrochloride led to a significant downregulation of inflammatory cytokines in all groups (P<0.05). Additionally, the expression levels of apoptosis-related proteins significantly increased, while Bcl-2 mRNA expression decreased (P<0.05). The mRNA expression levels of the PI3K/mTOR/AKT3 signaling pathway also decreased (P<0.05). At the protein expression level, in comparison to the control group, the levels of inflammatory cytokines IL-6, IL-8, IL-1β, and TGF-β were significantly downregulated in the middle and high-dose sinomenine hydrochloride groups (P<0.05). The expression levels of cleaved-PARP, cleaved caspase-3/7, and Bax increased and were positively correlated with the dose, while the expression levels of the anti-apoptotic protein Bcl-2 and the PI3K/AKT3/mTOR signaling pathway were negatively correlated with the dose. Sinomenine hydrochloride exhibited a significant inhibitory effect on the viability of rabbit knee joint fibroblasts, which may be associated with the downregulation of inflammatory cytokines IL-6, IL-8, and IL-1β, promotion of apoptosis-related proteins cleaved-PARP, cleaved caspase-3/7, and Bax, suppression of Bcl-2 expression, and inhibition of gene expression in the downstream PI3K/AKT3/mTOR signaling pathway. ConclusionSinomenine hydrochloride can inhibit the inflammatory response of fibroblasts in adhesive knee joints and accelerate fibroblast apoptosis. This mechanism may offer a novel approach to improving and treating knee joint adhesion.

The thinking process of medical diagnosis requires a comprehensive and analytical judgment.However,in both judgment processes,human thinking has inevitable limitations.With the development of artificial intelligence(AI)technology,symbolism and connectionism can effectively compensate for the deficiencies of human thinking in some respects,making more accurate diagnostic judgments,but they also have their limitations.It is conceivable that the integration and development of symbolism and connectionism will assist in enhancing the capabilities of medical-assisted diagnosis.However,there is still a tension between accuracy,transparency,and interpretability regarding the application of connectionism in AI,and many concerns about AI have arisen due to its lack of transparency and interpretability.By sorting out the thought process of medical diagnosis,organizing the differences among various AI paradigms and the changes in semantic philosophy and truth concepts behind AI,ethical concerns about the application of AI can be alleviated to a certain extent,and the practical application of AI in the field of medical diagnosis can be promoted.

AIM:To investigate the role of ClC-3 chloride channel in the promotion of radio sensitization of na-sopharyngeal carcinoma CNE-2Z cells by dihydroartemisinin(DHA).METHODS:MTT was used to detect the inhibito-ry effect of DHA on the viability of CNE-2Z cells and normal nasopharyngeal epithelial NP69-SV40T cells,the radio sensi-tization effect of DHA on CNE-2Z cells was detected by cloning assay,the expression of ClC-3 protein was detected by Western blot,the expression of ClC-3 protein was down-regulated by siRNA technology,and the chlorine current of cells was recorded by whole cell patch-clamp technology.RESULTS:(1)Compared with NP69-SV40T cells,DHA selective-ly inhibited the proliferation of CNE-2Z cells,with IC10 values of(13.020±4.831)μmol/L and(5.244±1.050)μmol/L,respectively(P＜0.01).(2)The results of clonal formation experiments showed that DHA had a radio sensitizing effect on CNE-2Z cells,with a radio sensitization ratio of 1.9.(3)DHA could activate the chlorine channel of CNE-2Z cells and produce an outward chlorine current,but had no effect on the chlorine channel of NP69-SV40T cells.(4)DHA promoted the expression of ClC-3 chloric channel protein in CNE-2Z cells(P＜0.01).(5)Chlorine channel blocker NPPB could in-hibit the radio sensitizing effect of DHA on CNE-2Z cells by 1.84 times,and also inhibited the chlorine current activated by DHA.(6)the down-regulation of CNE-2Z ClC-3 protein could inhibit the radio sensitization effect of DHA on CNE-2Z cells by 4.19 times,and the activation of chlorine current by DHA on CNE-2Z cells was no longer produced.CONCLU-SION:DHA has a radio sensitizing effect on nasopharyngeal carcinoma CNE-2Z cells,which is likely to be related to the activation of ClC-3 chloride channel.

Nanozymes, a groundbreaking discovery by Chinese scientists, represent a novel and remarkable property of nanomaterials. They not only exhibit catalytic activity comparable to natural enzymes, but also boast exceptional stability, tunable reactivity, and the ability to catalyze reactions under mild conditions. The identification of nanozymes has unveiled the biocatalytic potential of inorganic nanomaterials. In parallel, inorganic minerals have long been regarded as pivotal catalysts in the origin of life, driving the synthesis of early biomolecules. These minerals not only facilitate redox reactions that convert simple inorganic compounds into organic molecules but also enable chiral selection, the synthesis of biomacromolecules, and radioprotective functions via their surface structures. Recent advances suggest that inorganic nanomaterials can delicately catalyze the formation of biomolecules, aid in macromolecular assembly, and provide radiation shielding. Furthermore, nanominerals are found in abundance across Earth and extraterrestrial environments. This paper seeks to explore the potential of nanozymes as catalytic agents in the processes that gave rise to life, integrating the catalytic roles of inorganic minerals with the unique attributes of nanozymes, which will provide a new perspective for research of origin of life.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Traditional decoction pieces have low efficiency, poor batch-to-batch consistency, and irregular physical form, making it difficult to meet the demands of modern automated production and precise and rapid clinical blending. Therefore, this study aims to develop a new type of granular drinking tablet to meet the demand for high-quality development in the traditional Chinese medicine industry. In the current study, the differences and similarities between the new Lonicerae Japonicae Flos (LJF) granular drinking tablets and the traditional ones were evaluated based on the flowability, the paste rate of the standard soup, the characterization fingerprint, the degree of pasting, the content of active ingredients, the transfer rate, and its traditional antipyretic and anti-inflammatory efficacy, using the traditional LJF decoction piece as a reference. The flowability experiments showed that the flowability of medium-sized granules (10-24 mesh) was significantly better than that of traditional drinking tablets (P < 0.01); the results of the paste rate showed that there was no significant difference between the different particle sizes and the original decoction pieces (P > 0.05), but the small particle sizes (24-65 mesh) had poor decoction clarity and gelatinization; the transfer rate was calculated as chlorogenic acid and luteoloside, and there was no significant difference in the transfer rate between traditional slices and different particle sizes (P > 0.05); the pharmacological results showed that the contents of rat tumor necrosis factor-α (TNF-α), rat interleukin-1β (IL-1β) and rat prostaglandin E₂ (PGE₂), xylene ear swelling inhibition rate and granuloma inhibition rate showed that there was no significant difference between the traditional and new granule decoction pieces (P > 0.05). In this study, by examining the fluidity, paste rate, paste degree, and antipyretic and anti-inflammatory effects of the new granular decoction piece of LJF, it was initially revealed that the new granular drinking tablets of LJF were consistent with the basic properties and pharmacological effects of the commercially available traditional drinking tablets. Still, the new granular tablets were characterized by high utilization rate, homogeneous quality, and ease of clinical transfer, which had a good prospect for application. The animal experiment was approved by the Ethics Committee of the China Academy of Chinese Medical Sciences (approval number. 2022B214).

Objective This study aims to elucidate the protective role of Acacetin against apoptosis in HP-infected GES-1 cells and to delineate its potential underlying mechanisms.Materials and Methods GES-1 cells were subjected to in vitro treatment with HP and Acacetin.Cell viability was assessed utilizing the CCK-8 assay,alterations in cell migration and healing capacities through the wound healing assay,rates of apoptosis via flow cytometry,and expression levels of apoptosis-associated proteins through western blot analysis.Results HP infection led to a diminution in GES-1 cell viability,a suppression of cell migration,an augmentation in the rate of apoptosis,and an increase in the expression levels of Bax and cle-caspase3.Conversely,treatment with Acacetin was found to enhance cell viability,mitigate apoptosis induced by HP infection,and modulate the expression of apoptosis proteins by downregulating Bax and cle-caspase3.Discussion and Conclusion Acacetin significantly improves GES-1 cell vitality and inhibits apoptosis in HP-infected GES-1 cells,thereby offering a protective effect on gastric mucosal epithelial cells.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.