To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans ; Male ; Penis/abnormalities* ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Treatment Outcome ; Child ; Plastic Surgery Procedures/methods*

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Geriatric oral health care encounters significant challenges with the increase in the proportion of older individuals. Age-related changes in the dentition, muscles, and joints result in a decline in objective masticatory function, subjective restoration requirements, and acceptability among the elderly population, with individual variations influenced by systemic health. Considering functional requirements, the adaptability of stomatognathic and systemic health conditions, health economics and other factors, the authors believe that it should not be limited to the conventional "one-to-one" strategy for replacing missing teeth in geriatric prosthodontics. There is an urgent need for a precise and adaptable restoration strategy that is more suitable for older individuals. The proposal of a new concept of functional tooth loss updates the minimal restoration standards for elderly patients and establishes the theory of age-friendly functional restoration. Based on the restoration strategy of functional tooth loss, this paper proposes a new concept termed "age-friendly functional restoration of the stomatognathic system", which integrates treatment considerations including endodontics, periodontology, mucosa, muscles, temporomandibular joint, and systemic health. Efforts should be made in four areas as follows. Firstly, the "assessment of accessible function" should be enhanced by considering the interrelationship between stomatognathic and systemic health. Secondly, the "evaluation of appropriate function" is supposed to be optimised in view of subjective needs and objective evaluation of the stomatognathic system. Moreover, the "formulation of treatment plans" needs to be accomplished with the aid of assistive technologies, such as artificial intelligence, to accurately exert appropriate functional restoration. Lastly, the "management and maintenance of health" is likely to be strengthened through follow-ups, propaganda and education, and preventive healthcare, so as to improve quality of life and ultimately achieve healthy ageing among older individuals.
Humans ; Tooth Loss/therapy* ; Aged ; Stomatognathic System ; Oral Health ; Dental Care for Aged ; Dental Restoration, Permanent/methods*

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection. Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120 after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05). Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14-28 d)on the immunization potential.

Objective To explore the therapeutic material basis and antitussive mechanism of Ganke Formula.Methods Ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF/MS)technology was used to analyze and identify the components of Ganke Formula in serum.30 rats were randomly divided into control group,model group,experimental-L group,experimental-M group and experimental-H group,6 rats per group.Acute bronchitis rat model was established by smoke inhalation and cold stimulus.The experimental-L,-M,-H groups were respectively given 1.86,4.66,9.32 g·kg-1(crude drug/weight)dose of Ganke Formula per day by intragastric administration for 7 days.The control group and model group were given the equal amount of normal saline.The contents of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in rat lung tissue were determined by enzyme-linked immunosorbent assay.The expressions of phosphatidylinositol 3-kinase(PI3K)and phosphorylated protein kinase B(p-Akt)in lung were detected by Western blotting.Results Twenty-six absorbed components have been identified by UPLC-Q-TOF/MS.The contents of IL-1β in control group,model group,experimental-M,-H group were(57.80±7.67),(186.48±8.50),(166.05±9.90)and(143.19±6.31)pg·mL-1;TNF-α contents were(47.14±8.55),(316.22±9.49),(68.93±7.94)and(65.93±7.10)pg·mL-1;the relative expression levels of PI3K in lung tissues were 0.38±0.05,0.97±0.10,0.68±0.15 and 0.56±0.10;the relative expression levels of p-Akt were 0.34±0.14,0.93±0.05,0.63±0.16 and 0.49±0.14,respectively.Compared with the model group,the above indicators in the experimental-H group and control group were statistically different(P＜0.01 or P＜0.05).Conclusion Ganke Formula can intervene in the expression of inflammatory and immune regulatory factors by regulating PI3K/Akt signaling pathway,improve airway inflammation,and thus exert cough relieving effects.

AIM To explore the clinical effects of Bushen Huoxue Ointment Formula on patients with ankylosing spondylitis of Kidney Deficiency and Blood Stasis Pattern.METHODS One hundred and sixty-seven patients were randomly assigned into control group(55 cases)for 2-year intervention of conventional treatment,exposure group(54 cases)for 2-year intervention of both Bushen Huoxue Decoction and conventional treatment,and high exposure group(58 cases)for 2-year intervention of Bushen Huoxue Ointment Formula,Bushen Huoxue Decoction and conventional treatment.The changes in clinical effects,BASDAI score,ASDAS-CRP,BASFI score,spinal pain score,PGA score,BASMI score,ASQoL score,SPARCC score,Kidney Deficiency and Blood Stasis Pattern score,ESR,CRP,IL-6,TNF-α,IL-17,IL-23,IL-35,NLR,PLR and safety indices were detected.RESULTS The high exposure group demonstrated more ASAS40,ASASAS5/6,BASDAI50 cases than the exposure group and the control group(P<0.05).After the treatment,the high exposure group displayed lower BASDAI score,ASDAS-CRP,BASFI score,spinal pain score,PGA score,BASMI score,SPARCC score,ASQoL score,Kidney Deficiency and Blood Stasis Pattern score,ESR,CRP,IL-6,TNF-α,IL-17,IL-23 than the other two groups(P<0.05),and higher IL-35(P<0.05).After adjusting confounding factors by logistic regression analysis,Bushen Huoxue Decoction and Bushen Huoxue Ointment Formula reduced BASDAI score,ASDAS-CRP(P<0.05),and enhanced clinical effects(P<0.05).No serious adverse reactions were found in the three groups.CONCLUSION For the patients with ankylosing spondylitis of Kidney Deficiency and Blood Stasis Pattern,Bushen Huoxue Ointment Formula can safely and effectively inhibit inflammation,reduce disease activity,alleviate bone marrow edema,improve clinical symptoms,and enhance joint functions and life quality.

OBJECTIVE To establish the project approval evaluation system for traditional Chinese medicine （TCM） preparations in medical institutions guided by new drug conversion， to improve the success rate of approval for TCM preparations in medical institutions and lay the foundation for the later drug conversion. METHODS Research and development team used the literature research method and brainstorming method to list and organize relevant elements of project evaluation and determine the initial indicator system. Experts were consulted using the Delphi method to confirm the evaluation index. The weights were calculated based on the proportion of importance scores for each indicator and assigned specific scores to each item. The indicator system was used to evaluate 31 TCM preparations applied for filing by various departments of our hospital from April to July 2023. RESULTS After two rounds of 17 experts’ consultation， the final TCM preparation system included five primary indicators， i.e. theoretical basis， clinical research foundation， pharmaceutical foundation， prescription， and clinical value， as well as 17 secondary indicators including prescription source， traditional Chinese medicine theory， clinical positioning and so on. Human experience was considered as the item which would be rejected as one vote. Based on the above indicator system， our hospital further improved the filing and project approval process for TCM preparations in medical institutions. Among the 31 TCM preparations applied for filing by various departments from April to July 2023， 8 TCM preparations with a score ≥65 were selected for development. CONCLUSIONS The evaluation system is objective， comprehensive， and highly operable. It is suitable for the selection of TCM preparations in medical institutions before research and development.

Objective:To investigate the effect of tofacitinib,a pan-Janus kinase(JAK)inhibitor,on transforming growth factor-beta 1(TGF-β1)-induced fibroblast to myofibroblast transition(FMT)and to explore its mechanism.To provide a theoretical basis for the clinical treatment of connective tissue disease-related interstitial lung disease(CTD-ILD).Methods:(1)Human fetal lung fibroblast 1(HFL-1)were cultured in vitro,and 6 groups were established:DMSO blank control group,TGF-β1 in-duction group,and TGF-β1 with different concentrations of tofacitinib(0.5,1.0,2.0,5.0 μmol/L)drug intervention experimental groups.CCK-8 was used to measure the cell viability,and wound-healing assay was performed to measure cell migration ability.After 48 h of combined treatment,quantitative real-time PCR(RT-PCR)and Western blotting were used to detect the gene and protein expression levels of α-smooth muscle actin(α-SMA),fibronectin(FN),and collagen type Ⅰ(COL1).(2)RT-PCR and enzyme-linked immunosorbnent assay(ELISA)were used to detect the interleukin-6(IL-6)gene and protein expression changes,respectively.(3)DMSO carrier controls,1.0 μmol/L and 5.0 μmol/L tofacitinib were added to the cell culture media of different groups for pre-incubation for 30 min,and then TGF-β1 was added to treat for 1 h,6 h and 24 h.The phosphorylation levels of Smad2/3 and signal transducer and activator of transcription 3(STAT3)protein were detected by Western blotting.Results:(1)Tofacitinib inhibited the viability and migration ability of HFL-1 cells after TGF-β1 induction.(2)The expression of α-SMA,COL1A1 and FN1 genes of HFL-1 in the TGF-β1-induced groups was signifi-cantly up-regulated compared with the blank control group(P＜0.05).Compared with the TGF-β1 in-duction group,α-SMA expression in the 5.0 μmol/L tofacitinib intervention group was significantly inhi-bited(P＜0.05).Compared with the TGF-β1-induced group,FN1 gene was significantly inhibited in each intervention group at a concentration of 0.5-5.0 μmol/L(P＜0.05).Compared with the TGF-β1-induced group,the COL1A1 gene expression in each intervention group did not change significantly.(3)Western blotting results showed that the protein levels of α-SMA and FN1 in the TGF-β1-induced group were significantly higher than those in the control group(P＜0.05),and there was no significant difference in the expression of COL1A1.Compared with the TGF-β1-induced group,the α-SMA protein level in the intervention groups with different concentrations decreased.And the differences between the TGF-β1-induced group and 2.0 μmol/L or 5.0 μmol/L intervention groups were statistically significant(P＜0.05).Compared with the TGF-β1-induced group,the FN1 protein levels in the intervention groups with different concentrations showed a downward trend,but the difference was not statistically sig-nificant.There was no difference in COL1A1 protein expression between the intervention groups com-pared with the TGF-β1-induced group.(4)After TGF-β1 acted on HFL-1 cells for 48 h,the gene ex-pression of the IL-6 was up-regulated and IL-6 in culture supernatant was increased,the intervention with tofacitinib partly inhibited the TGF-β1-induced IL-6 gene expression and IL-6 in culture supernatant.TGF-β1 induced the increase of Smad2/3 protein phosphorylation in HFL-1 cells for 1 h and 6 h,STAT3 protein phosphorylation increased at 1 h,6 h and 24 h,the pre-intervention with tofacitinib inhibited the TGF-β1-induced Smad2/3 phosphorylation at 6 h and inhibited TGF-β1-induced STAT3 phosphorylation at 1 h,6 h and 24 h.Conclusion:Tofacitinib can inhibit the transformation of HFL-1 cells into myofi-broblasts induced by TGF-β1,and the mechanism may be through inhibiting the classic Smad2/3 path-way as well as the phosphorylation of STAT3 induced by TGF-β1,thereby protecting the disease progres-sion of pulmonary fibrosis.