In silico analysis of the wild-type and mutant-type of BRCA2 gene.

BACKGROUND: The aim of this study was to conduct an in silico analysis of a novel compound heterozygous variant in breast cancer susceptibility gene 2 (BRCA2) to clarify its structure-function relationship and elucidate the molecular mechanisms underlying triple-negative breast cancer (TNBC). METHODS: A tumor biopsy sample was obtained from a 42-year-old Chinese woman during surgery, and a maxBRCA™ test was conducted using the patient's whole blood. We obtained an experimentally determined 3D structure (1mje.pdb) of the BRCA2 protein from the Protein Data Bank (PDB) as a relatively reliable reference. Subsequently, the wild-type and mutant structures were predicted using SWISS-MODEL and AlphaFold, and the accuracy of these predictions was assessed through the SAVES online server. Furthermore, we utilized a high ambiguity-driven protein-protein docking (HADDOCK) algorithm and protein-ligand interaction profiler (PLIP) to predict the pathogenicity of the mutations and elucidate pathogenic mechanisms that potentially underlies TNBC. RESULTS: Histological examination revealed that the tumor biopsy sample exhibited classical pathological characteristics of TNBC. Furthermore, the maxBRCA™ test revealed two compound heterozygous BRCA2 gene mutations (c.7670 C > T.pA2557V and c.8356G > A.pA2786T). Through performing in silico structural analyses and constructing of 3D models of the mutants, we established that the mutant amino acids valine and threonine were located in the helical domain and oligonucleotide binding 1 (OB1), regions that interact with DSS1. CONCLUSION: Our analysis revealed that substituting valine and threonine in the helical domain region alters the structure and function of BRCA2 proteins. This mutation potentially affects the binding of proteins and DNA fragments and disrupts interactions between the helical domain region and OB1 with DSS1, potentially leading to the development of TNBC. Our findings suggest that the identified compound heterozygous mutation contributes to the clinical presentation of TNBC, providing new insights into the pathogenesis of TNBC and the influence of compound heterozygous mutations in BRCA2.

Laparoscopic treatment of a patient with multiple organ dysfunction syndrome induced by necrotising fasciitis.

Necrotising fasciitis (NF) is an uncommon surgical emergency that threatens the life and health of patients. We report the treatment of a 76-year-old female patient with NF. The patient developed NF due to chronic poor glycaemic control, which further progressed to multiple organ dysfunction syndrome due to the severity of the hyperglycaemia. After resuscitation at the intensive care unit, surgical treatment was recommended and the patient underwent laparoscopic surgery. She had an uneventful post-operative recovery with aggressive anti-inflammatory therapy, glycaemic control and systemic nutritional support. There were no recurrences during the next 6 months of follow-up. NF should be diagnosed and treated as early as possible to gain valuable treatment time for the patient. Laparoscopic surgery is a treatment option.

Diagnosis and therapy of giant epidermoid double cysts with infection on the buttock: A case report and literature review.

RATIONALE: Epidermoid cyst (EC) is a common clinical condition and it can be filled with keratinized material. EC often represents painless, slow progressive growth, and single cyst. The cyst is usually 1 to 5 cm in size. Giant epidermoid cysts on the buttock area are extremely rare, and reports of giant epidermoid double cysts on the buttock are even rarer. PATIENT CONCERNS: This paper reports a patient with a painless mass was on the left buttock. DIAGNOSIS: A giant epidermoid double cysts with infection in a left buttock paranal location. INTERVENTIONS: The mass was surgically removed. OUTCOMES: The patient recovered well after surgical treatment and currently has no recurrence. CONCLUSION: For patients with EC, MRI is recommended as a routine examination before surgery in order to detect the variation and extent of the cyst early. This lays a foundation for the complete resection of the lesion during the operation. The review of relevant literature will hopefully be helpful to clinicians.

Mechanisms and effects of NLRP3 in digestive cancers.

Inflammasomes are thought to be important mediators of host defense against microbial pathogens and maintenance of gastrointestinal tract homeostasis. They can modulate caspase-1 to promote IL-18 and IL-1ß secretion and promote phagocytosis induced by bacterial pathogens. NLRP3 is an inflammasome comprising a multiprotein complex assembled by pattern recognition receptors in the cell cytoplasm. It is a crucial component of the innate immune system. Dysregulation of NLRP3 may contribute to inflammatory diseases and intestinal cancers. Recent research suggests that NLRP3 plays an essential role in tumor development; therefore, intensive study of its mechanism is warranted as it could play a key role in the treatment of digestive system tumors. In this review, we discuss the mechanism and role of NLRP3 in tumors of the digestive system and response strategies to modulate NLRP3 for potential use in tumor treatment.

Gut Microbiome and Stroke: a Bidirectional Mendelian Randomisation Study in East Asian and European Populations.

BACKGROUND AND AIMS: Observational studies have implicated the involvement of gut microbiome in stroke development. Conversely, stroke may disrupt the gut microbiome balance, potentially causing systemic infections exacerbated brain infarction. However, the causal relationship remains controversial or unknown. To investigate bidirectional causality and potential ethnic differences, we conducted a bidirectional two-sample Mendelian randomisation (MR) study in both East Asian (EAS) and European (EU) populations. METHODS: Leveraging the hitherto largest genome-wide association study (GWAS) summary data from the MiBioGen Consortium (n=18 340, EU) and BGI (n=2524, EAS) for the gut microbiome, stroke GWAS data from the GIGASTROKE Consortium(264 655 EAS and 1 308 460 EU), we conducted bidirectional MR and sensitivity analyses separately for the EAS and EU population. RESULTS: We identified nominally significant associations between 85 gut microbiomes taxa in EAS and 64 gut microbiomes taxa in EU with stroke or its subtypes. Following multiple testing, we observed that genetically determined 1 SD increase in the relative abundance of species Bacteroides pectinophilus decreased the risk of cardioembolic stroke onset by 28% (OR 0.72 (95% CI 0.62 to 0.84); p=4.22e-5), and that genetically determined 1 SD increase in class Negativicutes resulted in a 0.76% risk increase in small vessel stroke in EAS. No significant causal association was identified in the EU population and the reverse MR analysis. CONCLUSION: Our study revealed subtype-specific and population-specific causal associations between gut microbiome and stroke risk among EAS and EU populations. The identified causality holds promise for developing a new stroke prevention strategy, warrants further mechanistic validation and necessitates clinical trial studies.

Clinical application of transcranial magnetic stimulation for functional bowel disease.

Functional bowel disorder (FBD) is a common gastrointestinal disease syndrome characterized by dysmotility and secretion without known organic lesions. The pathogenesis of FBD is still unclear. In recent years, with the rise of neurogastroenterology, it has initially revealed its close relationship with the "brain-gut axis." Transcranial magnetic stimulation (TMS) is a technique for detecting and treating the nervous system, that is characterized by non-invasiveness and painlessness. TMS plays an important role in the diagnosis and treatment of diseases, and provides a new method for the treatment of FBD. In this paper, we summarized and analyzed the research progress of using TMS therapy applied to patients with irritable bowel syndrome and functional constipation by domestic and foreign scholars in recent years by means of literature search, and found that TMS therapy could improve the intestinal discomfort and accompanying mental symptoms in patients with FBD.

Prognostic model construction and immune microenvironment analysis of esophageal cancer based on gene expression data and microRNA target genes.

Background: Accumulating evidence suggests that microRNA-target genes are closely related to tumorigenesis and progression. This study aims to screen the intersection of differentially expressed mRNAs (DEmRNAs) and the target genes of differentially expressed microRNAs (DEmiRNAs), and to construct a prognostic gene model of esophageal cancer (EC). Methods: Gene expression, microRNA expression, somatic mutation, and clinical information data of EC from The Cancer Genome Atlas (TCGA) database were used. The intersection of DEmRNAs and the target genes of DEmiRNAs predicted by the Targetscan database and microRNA Data Integration Portal (mirDIP) database were screened. The screened genes were used to construct a prognostic model of EC. Then, the molecular and immune signatures of these genes were explored. Finally, the GSE53625 dataset from the Gene Expression Omnibus (GEO) database was further used as a validation cohort to confirm the prognostic value of the genes. Results: Six genes on the grounds of the intersection of DEmiRNAs target genes and DEmRNAs were identified as prognostic genes, including ARHGAP11A, H1.4, HMGB3, LRIG1, PRR11, and COL4A1. Based on the median risk score calculated for these genes, EC patients were divided into a high-risk group (n=72) and a low-risk group (n=72). Survival analysis showed that the high-risk group had a significantly shorter survival time than the low-risk group (TCGA and GEO, P<0.001). The nomogram evaluation showed high reliability in predicting the 1-year, 2-year, and 3-year survival probability of EC patients. Compared to low-risk group, higher expression level of M2 macrophages was found in high-risk group of EC patient (P<0.05), while STAT3 checkpoints showed attenuated expression level in high-risk group. Conclusions: A panel of differential genes was identified as potential EC prognostic biomarkers and showed great clinical significance in EC prognosis.

Progress in the surgical treatment of sacrococcygeal pilonidal sinus: a review.

BACKGROUND: A pilonidal sinus (PS) is an acquired disease resulting from recurrent infections and chronic inflammation. A PS involving the sacrococcyx is referred to as a sacrococcygeal PS (SPS). An SPS is a rare chronic infectious disease for which surgery is a good choice. The incidence of SPS has gradually increased worldwide in recent years. However, surgeons have not reached a consensus on the preferred surgical approach for SPS. The authors performed a systematic review and meta-analysis to analyze differences in the efficacy of different surgical approaches for the treatment of SPS. METHODS: A systematic search was conducted in the PubMed database covering the period from 1 January 2003, to 28 February 2023. The primary outcome parameters were recurrence and infection. Finally, statistical analysis (meta-analysis) was carried out using RevMan 5.4.1 software. In addition, we systematically reviewed the latest progress in the surgical treatment of SPS over the past 20 years, especially as reported in the past 3 years. RESULTS: Twenty-seven articles, 54 studies, and 3612 participants were included in this meta-analysis. The recurrence rate following the midline closure (MC) technique was much higher than that of other techniques. Among the techniques analyzed, the differences between MC and Limberg flap (LF), and between MC and marsupialization were statistically significant [ P =0.0002, risk ratio (RR)=6.15, 95% CI 2.40, 15.80; P =0.01, RR=12.70, 95% CI 1.70, 95.06]. The recurrence rate of open healing was higher than that of the Karydakis flap (KF) technique, and the difference was statistically significant ( P =0.02, RR=6.04, 95% CI 1.37, 26.55). Most of the results comparing MC with other techniques suggested that the former had a higher infection rate, and the difference between MC and LF was statistically significant ( P =0.0005, RR=4.14, 95% CI 1.86, 9.23). Comparison between KF and LF, modified LF and KF showed that the differences were not statistically significant in terms of recurrence and infection ( P ≥0.05). CONCLUSIONS: There are various surgical treatment options for SPS, including incision and drainage, excision of diseased tissue with primary closure and secondary healing, and minimally invasive surgery. It is still not possible to determine which surgical technique should be considered the gold standard for treatment, as even the results of different researchers using the same operation method are conflicting. But what is certain is that the midline closure technique has a much higher incidence of postoperative recurrence and infection than other techniques. Therefore, the anorectal surgeon should formulate the most suitable individualized plan for the patient based on a comprehensive evaluation of the patient's wishes, appearance of the SPS, and the professional ability of the surgeon.

Native doublet microtubules from Tetrahymena thermophila reveal the importance of outer junction proteins.

Cilia are ubiquitous eukaryotic organelles responsible for cellular motility and sensory functions. The ciliary axoneme is a microtubule-based cytoskeleton consisting of two central singlets and nine outer doublet microtubules. Cryo-electron microscopy-based studies have revealed a complex network inside the lumen of both tubules composed of microtubule-inner proteins (MIPs). However, the functions of most MIPs remain unknown. Here, we present single-particle cryo-EM-based analyses of the Tetrahymena thermophila native doublet microtubule and identify 42 MIPs. These data shed light on the evolutionarily conserved and diversified roles of MIPs. In addition, we identified MIPs potentially responsible for the assembly and stability of the doublet outer junction. Knockout of the evolutionarily conserved outer junction component CFAP77 moderately diminishes Tetrahymena swimming speed and beat frequency, indicating the important role of CFAP77 and outer junction stability in cilia beating generation and/or regulation.

Platelet lysate promotes hair growth: In vitro and in vivo mechanism and randomized, controlled trial.

BACKGROUND: Platelet lysate (PL), a novel platelet derivative, has been widely used in regenerative medicine and is a potential therapy for improving hair growth. It is necessary to fully clarify the potential mechanism and evaluate preliminary clinical effect of PL on hair growth. METHODS: We used the C57BL/6 model, organ-cultured hair follicles, and RNA-seq analysis to explore the mechanisms of PL regulating hair growth. Then, we performed a randomized, controlled, double-blind study of 107 AGA patients to verify the therapeutic efficacy of PL. RESULTS: The results confirmed that PL improved hair growth and accelerated hair cycling in mice. Organ-cultured hair follicle evaluation confirmed that PL prolonged anagen remarkably and down-regulated IL-6, C-FOS, and p-STAT5a. Clinically, diameter, hair counts, absolute anagen counts and changes from baseline in the PL group showed a significant improvement at 6 months. CONCLUSIONS: We elucidated the specific molecular mechanism of PL action on hair growth and proved equal changes in hair follicle performance after PL vs PRP in AGA patients. This study provided novel knowledge of PL, making it ideal for AGA.

Efficacy of Platelet-Rich Plasma plus Basic Fibroblast Growth Factor on the Treatment of Androgenic Alopecia.

BACKGROUND: Studies have identified platelet-rich plasma (PRP) as a novel adjuvant therapy in androgenetic alopecia (AGA). However, the efficacy of PRP still needs to be improved. The purpose of this study was to assess the efficacy of PRP plus basic fibroblast growth factor (PRPF) for the treatment of AGA. METHODS: This was a prospective randomized, double-blind, placebo-controlled, half-head study. Eighty patients whose AGA was staged Norwood-Hamilton stages III to VII or Ludwig stages I to III were enrolled in the study from February of 2019 to September of 2019. Patients were divided randomly into two groups of 40 patients each and were given the following treatment: group 1, PRPF was injected in the right half and the left half with placebo; group 2, PRPF was injected in the right half and the left half with PRP. The treatment was processed three times, 1 month apart. Hair growth parameters were evaluated by trichoscope monthly until the sixth month of the study. Patient satisfaction, hair pull test, and side effects were recorded during follow-up. RESULTS: Of the 80 patients included in the study, 47 were men and 33 were women with a mean age of 28.96 ± 4.82 years (range, 21 to 46 years). Both PRP and PRPF showed positive improvement ( P < 0.05) on hair count, terminal hair, and anagen hair after the treatment. Efficacy of PRPF revealed a significant improvement ( P < 0.05) in hair count, terminal hair, vellus hair, and anagen hair versus PRP. There was no statistical difference among any of the parameters in the placebo group. CONCLUSION: PRPF can be a safe and valuable form of AGA treatment, and has proven to be more effective than PRP. CLINICAL RELEVANCE STATEMENT: Hybrid therapy of PRP with relative growth factors, such as basic fibroblast growth factor, have prominent efficacy on treatment of AGA. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Recent therapeutics in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor of hepatocytes. It is a common malignant tumor of the digestive system that often has initially hidden presentation followed by rapid progression. There are no obvious symptoms in the early stage of HCC. When diagnosed, most patients have locally advanced tumor or distant metastasis; therefore, HCC is difficult to treat and only supportive and symptomatic treatment is adopted. The prognosis is poor and survival time is short. How to effectively treat HCC is important clinically. In recent years, advances in medical technology have resulted in comprehensive treatment methods based on surgery.

Rhizosphere phage communities drive soil suppressiveness to bacterial wilt disease.

BACKGROUND: Bacterial viruses, phages, play a key role in nutrient turnover and lysis of bacteria in terrestrial ecosystems. While phages are abundant in soils, their effects on plant pathogens and rhizosphere bacterial communities are poorly understood. Here, we used metagenomics and direct experiments to causally test if differences in rhizosphere phage communities could explain variation in soil suppressiveness and bacterial wilt plant disease outcomes by plant-pathogenic Ralstonia solanacearum bacterium. Specifically, we tested two hypotheses: (1) that healthy plants are associated with stronger top-down pathogen control by R. solanacearum-specific phages (i.e. 'primary phages') and (2) that 'secondary phages' that target pathogen-inhibiting bacteria play a stronger role in diseased plant rhizosphere microbiomes by indirectly 'helping' the pathogen. RESULTS: Using a repeated sampling of tomato rhizosphere soil in the field, we show that healthy plants are associated with distinct phage communities that contain relatively higher abundances of R. solanacearum-specific phages that exert strong top-down pathogen density control. Moreover, 'secondary phages' that targeted pathogen-inhibiting bacteria were more abundant in the diseased plant microbiomes. The roles of R. solanacearum-specific and 'secondary phages' were directly validated in separate greenhouse experiments where we causally show that phages can reduce soil suppressiveness, both directly and indirectly, via top-down control of pathogen densities and by alleviating interference competition between pathogen-inhibiting bacteria and the pathogen. CONCLUSIONS: Together, our findings demonstrate that soil suppressiveness, which is most often attributed to bacteria, could be driven by rhizosphere phage communities that regulate R. solanacearum densities and strength of interference competition with pathogen-suppressing bacteria. Rhizosphere phage communities are hence likely to be important in determining bacterial wilt disease outcomes and soil suppressiveness in agricultural fields. Video Abstract.

Using early health economic modeling to inform medical innovation development: a soft robotic sock in poststroke patients in Singapore.

OBJECTIVES: Based on a real-world collaboration with innovators in applying early health economic modeling, we aimed to offer practical steps that health technology assessment (HTA) researchers and innovators can follow and promote the usage of early HTA among research and development (R&D) communities. METHODS: The HTA researcher was approached by the innovator to carry out an early HTA ahead of the first clinical trial of the technology, a soft robotic sock for poststroke patients. Early health economic modeling was selected to understand the potential value of the technology and to help uncover the information gap. Threshold analysis was used to identify the target product profiles. Value-of-information analysis was conducted to understand the uncertainties and the need for further research. RESULTS: Based on the expected price and clinical effectiveness by the innovator, the new technology was found to be cost-saving compared to the current practice. Risk reduction in deep vein thrombosis and ankle contracture, the incidence rate of ankle contracture, the compliance rate of the new technology, and utility scores were found to have high impacts on the value-for-money of the new technology. The value of information was low if the new technology can achieve the expected clinical effectiveness. A list of parameters was recommended for data collection in the impending clinical trial. CONCLUSIONS: This work, based on a real-world collaboration, has illustrated that early health economic modeling can inform medical innovation development. We provided practical steps in order to achieve more efficient R&D investment in medical innovation moving forward.

Skullcapflavone II, a novel NQO1 inhibitor, alleviates aristolochic acid I-induced liver and kidney injury in mice.

Aristolochic acid I (AAI) is a well established nephrotoxin and human carcinogen. Cytosolic NAD(P)H quinone oxidoreductase 1 (NQO1) plays an important role in the nitro reduction of aristolochic acids, leading to production of aristoloactam and AA-DNA adduct. Application of a potent NQO1 inhibitor dicoumarol is limited by its life-threatening side effect as an anticoagulant and the subsequent hemorrhagic complications. As traditional medicines containing AAI remain available in the market, novel NQO1 inhibitors are urgently needed to attenuate the toxicity of AAI exposure. In this study, we employed comprehensive 2D NQO1 biochromatography to screen candidate compounds that could bind with NQO1 protein. Four compounds, i.e., skullcapflavone II (SFII), oroxylin A, wogonin and tectochrysin were screened out from Scutellaria baicalensis. Among them, SFII was the most promising NQO1 inhibitor with a binding affinity (KD = 4.198 µmol/L) and inhibitory activity (IC50 = 2.87 µmol/L). In human normal liver cell line (L02) and human renal proximal tubular epithelial cell line (HK-2), SFII significantly alleviated AAI-induced DNA damage and apoptosis. In adult mice, oral administration of SFII dose-dependently ameliorated AAI-induced renal fibrosis and dysfunction. In infant mice, oral administration of SFII suppressed AAI-induced hepatocellular carcinoma initiation. Moreover, administration of SFII did not affect the coagulation function in short term in adult mice. In conclusion, SFII has been identified as a novel NQO1 inhibitor that might impede the risk of AAI to kidney and liver without obvious side effect.

Mechanism and application of ferroptosis in colorectal cancer.

Colorectal cancer (CRC) is the third most common malignant tumor in the world. CRC has high morbidity and mortality rates and it is a serious threat to human health. Ferroptosis is a unique form of iron-dependent oxidative cell death that is usually accompanied by iron accumulation and lipid peroxidation. Ferroptosis has attracted worldwide attention since it was first proposed. It plays an important role in the development of a variety of diseases, such as tumors, ischemia/reperfusion injury, nervous system diseases, and kidney damage, and it may serve as a new therapeutic target. This article reviews the mechanism of ferroptosis and the possibility to target ferroptosis pathways in CRC, providing new ideas for the diagnosis and treatment of CRC.

Meckel's Diverticulum with Multiple Sprouts at the Tip in a Child.

Background: Meckel's diverticulum (MD) is usually a simple tubular-shaped diverticulum. Case report: We describe a MD with multiple complex terminal sprouts in a child found incidentally during an appendectomy for appendicitis. The MD was resected, and the child recovered well. Conclusion: MD may show multiple sprouts. There was no additional clinical consequence in this child with the malformed MD.

Associations between exposure to brominated flame retardants and metabolic syndrome and its components in U.S. adults.

BACKGROUND: Humans are simultaneously exposed to numerous of environmental brominated flame retardants (BFRs). We aim to explore the overall associations of BFRs mixture on metabolic syndrome (MetS) and its components and further identify significant chemicals. METHODS: This study included 4641 adults from the National Health and Nutrition Examination Survey (NHANES) in 2007-2016. The weighted logistic regression was conducted to estimate the association of a single BFR exposure with MetS and its components. Meanwhile, the weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were adopted to evaluate the overall associations of BFRs mixture on MetS and its components, and to identify significant chemicals. We also evaluated potential associations modified by sex. RESULTS: In the weighted logistic regression model, PBB153 were positively associated with MetS in a dose-dependent manner (Ptrend < 0.05). For its components, increasing quartiles of most BFRs were positively associated with abdominal obesity, hypertriglyceridemia, and low HDL. However, we found no statistically significant associations between BFRs and hypertension and hyperglycemia. WQS analyses found that BFRs mixture was positively associated with MetS (OR: 1.30; 95%CI:1.14, 1.46), abdominal obesity (OR: 1.15; 95%CI:1.03, 1.27), hypertriglyceridemia (OR:1.43; 95%CI:1.19, 1.67), and low HDL (OR: 1.15; 95%CI:1.01, 1.29). BKMR showed associations in a similar direction as WQS for BFRs mixture. For MetS, hypertriglyceridemia and Low HDL, PBB153, PBDE28 and PBDE209 were the most heavily weighting chemicals and had the highest the posterior inclusion probabilities in the WQS and BKMR, respectively. BFRs showed stronger associations of MetS and its components in males than in females. CONCLUSIONS: The present study suggested exposure to BFRs mixture was positively associated with MetS and its components in adults, and PBB153, PBDE28 and PBDE209 were the significant chemicals. However, prospective cohort studies are still needed to confirm the causal effect between BFRs mixture and MetS.

Modeling human gray hair by irradiation as a valuable tool to study aspects of tissue aging.

As one of the earliest and most visible phenomenon of aging, gray hair makes it a unique model system for investigating the mechanism of aging. Ionizing radiation successfully induces gray hair in mice, and also provides a venue to establish an organ-cultured human gray hair model. To establish a suitable organ-cultured human gray HF model by IR, which imitates gray hair in the elderly, and to explore the mechanisms behind the model. By detecting growth parameters, melanotic and senescence markers of the model, we found that the model of 5 Gy accords best with features of elderly gray hair. Then, we investigated the formation mechanisms of the model by RNA-sequencing. We demonstrated that the model of organ-cultured gray HFs after 5 Gy irradiation is closest to the older gray HFs. Moreover, the 5 Gy inhibited the expression of TRP-1, Tyr, Pmel17, and MITF in hair bulbs/ORS of HFs. The 5 Gy also significantly induced ectopically pigmented melanocytes and increased the expression of DNA damage and senescence in HFs. Finally, RNA-seq analysis of the model suggested that IR resulted in cell DNA damage, and the accumulation of oxidative stress in the keratinocytes. Oxidative stress and DNA damage caused cell dysfunction and decreased melanin synthesis in the gray HFs. We found that HFs irradiated at 5 Gy successfully constructed an appropriate aging HF model. This may provide a useful model for cost-effective and predictable treatment strategies to human hair graying and the process of aging.

The role of repetitive transcranial magnetic stimulation therapy in functional bowel disease.

Objective: This study investigates the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a biophysical therapy for alleviating symptoms of functional bowel disorder (FBD) and associated psychological symptoms by targeting the brain-gut axis. Methods: We conducted a comparative analysis involving 226 subjects, comprising the FBD group (n = 113) and a healthy control group (n = 113). Within the FBD group, participants were further divided into those who received rTMS therapy (FBD treatment group, n = 63) and those who did not (FBD control group, n = 50). The FBD treatment group was subcategorized based on the number of rTMS treatments received. We evaluated various factors, including gender, age, monthly household income, daily activity level, and sleep quality, as potential risk factors for FBD. Severity assessments of FBD and associated symptoms (constipation, anxiety, depression, and somatization disorders) were conducted using validated scales before and after treatment. Results: Our findings revealed a higher incidence of FBD in women, with most cases emerging at age 50 or older. We identified lower monthly household income, reduced daily activity levels, and poorer sleep quality as factors associated with a higher likelihood of FBD. FBD patients exhibited higher scores for constipation, anxiety, depression, and somatization disorders compared to healthy controls. rTMS therapy was effective in reducing gastrointestinal symptoms, anxiety, depression, and somatization disorders among FBD patients. Notably, the extent of improvement was positively correlated with the number of rTMS sessions. No adverse effects were observed during the study. Conclusion: Our study underscores the efficacy of biophysical therapy, specifically repetitive transcranial magnetic stimulation, in mitigating FBD symptoms and associated psychological distress. The treatment's effectiveness is positively linked to the frequency of rTMS sessions.