T helper cells (Th cells) play an important role in periodontitis. During the progression of periodontitis, the levels of pro-inflammatory cytokines such as INF-γ and IL-17, which are produced by Th1 and Th17 cells, are elevated, while the levels of anti-inflammatory cytokines such as IL-4 and TGF-β, which are secreted by Th2 cells and regulatory T cells (Tregs), are diminished. Interventions using mesenchymal stem cells (MSCs) or their exosomes can alter the dynamics of helper T cell populations and their associated cytokine profiles, thereby mitigating the bone loss associated with periodontitis or even promoting bone regeneration. Mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to directly modulate Th cell activity through the proteins and microRNAs they transport. Recent studies indicate that MSC-exos carry immune-suppressive protein molecules: PD-L1 and IDO contribute to regulating the balance between Th17 and Tregs; TGF-β inhibits the proliferation of T lymphocytes while facilitating differentiation into Tregs by sustaining forkhead box protein O3 (FOXP3) and Smad expression; and CD73 catalyzes the conversion of monophosphate adenosine into adenosine, which interacts with A2A receptors on Th1 cells to induce apoptosis in Th1 cells. In addition, microRNAs exhibit immunoregulatory functions: periodontal ligament stem cell-derived exosomes contain miRNA-155-5p, which targets sirtuin-1 to suppress Th17 cell differentiation. Furthermore, evidence in rat models of periodontitis suggests that these exosomes may also carry miR-205-5p targeting XBP1 to restore the balance between Th17 and Tregs. Dental pulp stem cell-derived exosomes reestablish this balance via the miR-1246/Nfat5 axis. Bone marrow mesenchymal stem cell-derived exosomes harbor miR-1246, which targets ACE2 to promote differentiation towards Tregs. Moreover, MSC-exos can indirectly enhance the differentiation of Tregs through interactions with other immune entities, such as antigen-presenting cells or macrophages. This article reviews the changes and roles of helper T cells in periodontitis, as well as the regulatory role of exosomes on helper T cells, hoping to provide new ideas for immunotherapy in the treatment of periodontitis.

ObjectiveThis paper aims to use the digital muscle function assessment system Myoton PRO to assess the correlation between muscle tension，clinical characteristics， and traditional Chinese medicine（TCM） syndromes in patients with hepatolenticular degeneration ［also known as Wilson disease（WD）］. MethodsA total of 104 patients with WD accompanied by abnormal muscle tension（increased or decreased，hereinafter the same） who were hospitalized in the Brain Disease Centre of the First Affiliated Hospital of Anhui University of Chinese Medicine from April 2021 to November 2023 were selected，all of whom were subjected to TCM syndrome diagnosis and Myoton PRO for the measurement of F value of muscle tension，Goldstein， and UWDRS-N scales. The age of onset of the disease and disease duration were analyzed，and the differences and correlations of the above indexes in different TCM syndromes of WD were analyzed ResultsAmong the 104 patients with WD ，the phlegm and stasis syndrome was the most common（60 patients），followed by the damp-heat syndrome（33 patients），and the least common was the liver-kidney Yin deficiency syndrome（11 patients）. The F value of the phlegm and stasis syndrome group was higher than that of the liver-kidney Yin deficiency syndrome group and the damp-heat syndrome group（P<0.01）. The F value of the damp-heat syndrome group was higher than that of the liver-kidney Yin deficiency syndrome group（P<0.05），and the F value of the lower limbs of each group was higher than that of the upper limbs（P<0.01）. Goldstein and UWDRS-N scores of the patients in the phlegm and stasis syndrome group were higher than those in the damp-heat syndrome group and the liver-kidney Yin deficiency syndrome group（P<0.05）. There was no significant difference between the Goldstein and UWDRS-N scores of patients in the liver-kidney Yin deficiency syndrome group and the damp-heat syndrome group. Correlation analysis revealed that the age of onset and duration of the disease were positively correlated with the F values of the lower limbs（r=0.20，P<0.05，r=0.38，P<0.01）and had no significant correlation with those of the upper limbs. The F value levels of muscle tension of all limbs in the three groups of patients were positively correlated with the Goldstein and UWDRS-N scores（muscle tension of the upper limbs in the phlegm and stasis syndrome group，r=0.36，P<0.01，r=0.42，P<0.01. muscle tension of the lower limbs in the phlegm and stasis syndrome group，r=0.70，P<0.01，r=0.60，P<0.01. muscle tension of the upper limbs in the damp-heat syndrome group，r=0.64，P<0.01，r=0.53，P<0.01. muscle tension of the lower limbs in the damp-heat syndrome group，r=0.59，P<0.01，r=0.70，P<0.01. muscle tension of the upper limbs in the liver-kidney Yin deficiency syndrome group，r=0.70，P<0.01，r=0.74，P<0.01. muscle tension of the lower limbs in the liver-kidney Yin deficiency syndrome group，r=0.85，P<0.01，r=0.62，P<0.01）. Conlusion： The digital muscle function assessment system Myoton PRO can objectively evaluate the muscle tension level of patients with WD accompanied by abnormal muscle tension. This level has significant differences among different TCM syndromes and can evaluate the patient's condition to some extent.

Objective·To investigate the relation between urinary excretion of protein-bound uremic toxins(PBUTs)and upper urinary tract calculus.Methods·Residents aged 18?80 years in the community of Haitou,Danzhou city in Hainan Province were recruited.Basic information and diet for the last 3 d of the subjects were recorded.Their fasting sera and 24-hour urine samples were collected,and they also underwent ultrasound examination of kidneys and ureters.The subjects with upper urinary calculi detected by ultrasound or a clear history of upper urinary calculi were selected as the calculus group,and the others as the non-calculus group.The biochemical indicators related to the formation of calculus in blood and urine were detected,and the levels of PBUTs,including indoxyl sufate(IS),indole-3-acetic acid(IAA),and p-cresol sulfate(PCS)in blood and urine,as well as oxalic acid and citric acid in urine were detected by high-performance liquid chromatography.The related factors of upper urinary tract calculus formation were analyzed by multivariate Logistic regression.The correlations of urine PBUTs with urine uric acid,oxalic acid,and citric acid were analyzed by Spearman correlation test.Results·A total of 117 participants were screened out with 54 people in the calculus group and 63 people in the non-calculus group.There were no significant differences between the two groups in terms of gender,age,serum indicators,and prevalence of complications such as hypertension,diabetes,and hyperuricemia/gout.The 24-hour urine pH,calcium,uric acid,and chlorine in the calculus group were significantly higher than those in the non-calculus group(all P<0.05),while IS was significantly lower than that in the non-calculus group(P<0.05).Multivariate Logistic regression analysis showed that urinary IS(OR=0.929,95%CI 0.875?0.986,P=0.016)was related to the calculus formation independently,in addition to urinary calcium.The Spearman correlation analysis results showed that the levels of IAA(r=0.420,P=0.000)and PCS(r=0.307,P=0.001)in 24-hour urine were positively correlated with oxalic acid,PCS was positively correlated with uric acid(r=0.297,P=0.002),and IS was positively correlated with citric acid(r=0.289,P=0.002).Conclusion·In the population,a decrease in urinary excretion of IS may be an independent risk factor for the formation of upper urinary tract calculus,and PBUTs levels are correlated with levels of uric acid,oxalic acid,and citric acid.

Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.
Mice ; Animals ; Epilepsy, Temporal Lobe/pathology* ; Parvalbumins/metabolism* ; Parkinson Disease/pathology* ; Neurons/metabolism* ; Interneurons/physiology* ; Disease Models, Animal ; Brain/pathology*

OBJECTIVE To analyze the dose-adjusted concentrations of Posaconazole oral suspension in patients undergoing hematopoietic stem cell transplantation （HSCT） and their influential factors. METHODS Data were collected from hospitalized HSCT patients admitted to the First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital） from January 2021 to April whtwhm@yeah.net 2023 who took Posaconazole oral suspension for the prevention of invasive fungal disease （IFD） and received blood concentration of posaconazole. The rate of concentration attainment and clinical failure rate of posaconazole for the prevention of IFD were evaluated， and one-way and multiple linear regression analyses were performed for the influential factors of dose-adjusted concentrations （C0/D） of posaconazole. RESULTS A total of 44 patients were enrolled； the mean C0 of posaconazole in patients was （0.99±0.94） µg/mL， and 20 patients had a C0≥0.7 μg/mL， with a concentration attainment rate of 45.45% for the prevention of IFD； 13 cases were clinical failures， with a clinical failure rate of 29.55%. Of 24 patients who did not achieve C0/D of posaconazole for IFD prophylaxis， one patient was a clinical failure despite timely dose adjustment of posaconazole in seven patients； seven of the thirteen patients who did not undergo dose adjustment were clinical failures； and the remaining four patients were switched to other antifungal agents. The results of univariate analysis showed that gender， body mass index （BMI）， renal function， combined use of sodium phenytoin， omeprazole and metoclopramide had a significant effect on the C0/D of posaconazole （P＜0.05）； the results of multivariate linear regression analysis showed that gender， BMI and combined use of sodium phenytoin were the independent factors affecting the C0/D of posaconazole （P＜0.05）. CONCLUSIONS Significant individual differences are reflected in the blood concentration of Posaconazole oral suspension； gender， BMI and combined use of sodium phenytoin are independent factors affecting the C0/D of posaconazole.

OBJECTIVE To explore the research status of drug control institutions and to analyze the research hotspots and frontier trends, so as to provide references for further research.METHODS Taking CNKI as the data source of Chinese literature, Web of Science Core Collection as the data source of English literature. Using CiteSpace 6.1.R6 visualization tool software, visualization analysis was conducted to the research status of drug control institutions in China from the aspects of author-institution cooperation, keyword co-occurrence, keyword cluster and burst analysis. Meanwhile, draw the relevant maps to do the compare.RESULTS A total of 3 711 Chinese literatures and 2 650 English literatures were included. The number of literatures issued by Chinese drug control institutions showed a rising trend. Ma Shuangcheng was the most prolific author, and National Institutes for Food and Drug Control was the most prolific research institution. Current research hotspots included content determination, fingerprinting, identification evaluation, dissolution mechanism and related substances combining specific drugs, as well as biotechnology, nanomaterials and toxicological substitution technologies. Frontier research trends mainly included drug quality research integrating advanced analytical technology and measurement methods, detection technology of frontier biological products, and continuous research on antibacterial active substances. CONCLUSION Researchers and institutions should grasp hotspots and trends, work at deepen cooperation and research, and provide intellectual support for improving ability of drug inspection and promoting the modernization of drug supervision.

Objective: To construct the full-length prokaryotic expression plasmid of the wild type of androgen receptor (AR) and the truncated body of four functional domains，and to identify the fusion protein by Western blot and electrophoretic mobility shift assay ( EMSA) ． Methods: Based on the pGEX-4T-1 vector ，the recombinant plasmids were constructed to express the full-length and functional domains of AR. IPTG was used to induce the expression of the recombinant proteins，which were isolated and purified by glutathione sepharose 4B beads under the optimized condition．The specific protein expression in the bacterial lysate and the purified protein isolated with glutathione sepharose 4B beads was identified by Western blot with AR antibody and GST labeled antibody．The purified protein was incubated with a fluorescent probe of the virus，and the complex was detected by electrophoresis in a non-denaturing gel. Results : The prokaryotic recombinant plasmids of full length and three functional domain truncated AR were successfully constructed．The recombinant clones were identified by using bacterial culture as a template，and further verified by double enzyme digestion．It showed that there were identical bands in the same sizes as the inserted fragments．The nucleotide and the amino acid sequences were aligned to the reference sequence in NCBI GenBank．The GST fusion protein，GST-AR-NTD + DBD (96 ku) and GST-AR-NTD (86 ku) were successfully induced and verified． The purified protein could be directly combined with the viral genome DNA． Conclusion The prokaryotic expression conditions of truncated AR plasmid from the same gene sequence are different．The purified AR protein can be used to understand the direct interaction mechanism between functional domains of AR and other molecules.

In recent years, osteoporosis (OP) has become one of the main diseases affecting the health of middle-aged and elderly people in China, and the prevalence of OP has increased significantly. The clinical diagnosis and treatment guidelines for this disease are also constantly updated. The overall principles speciallyemphasise that doctors and patients need to work together to negotiate the details of the diagnosis and treatment guidelines, in order to improve the OP clinical diagnosis and treatment rate. Therefore, patients′ knowledge of the disease, understanding of clinical guidelines, and cooperation with doctors to implement diagnosis and treatment plans are very important. In this study, from the most concerned issues of the patients, we established the OP patient practice guideline working group. 14 recommendations, as the OP patient practice guidelines, are proposed in accordance with the relevant principles of the "World Health Organization guidelines development manual" and the international normative process.