Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is a rare autosomal dominant genetic disorder. It may also involve many other organ systems, leading to complications such as exocrine pancreatic insufficiency, liver dysfunction, lymphedema, and developmental delay. The FAM111B has been determined as the pathogenic gene associated with POIKTMP syndrome, whose protein product plays a critical role in regulating essential cellular processes including DNA repair and replication, cell cycle progression, apoptosis, nuclear transport, and telomere length maintenance. This article has provided a comprehensive review for the genetic basis of POIKTMP syndrome and its correlation with various phenotypes, which may offer insights for basic research and clinical diagnosis of this disease.
Humans ; Pulmonary Fibrosis/genetics* ; Skin Diseases, Genetic/genetics*

BACKGROUND

Sarcopenia is highly prevalent in patients with liver cirrhosis and contributes to decreased quality of life, increased morbidity, and mortality. The role of myostatin in cirrhosis-related sarcopenia remains controversial but may represent a potential therapeutic target.

OBJECTIVE

This study aimed to investigate the association between serum myostatin levels and sarcopenia in patients with liver cirrhosis.

METHODS

A cross-sectional study was conducted with 80 patients diagnosed with liver cirrhosis at Prof. Dr. I.G.N.G. Ngoerah General Hospital, Denpasar, Bali, Indonesia. Serum myostatin levels (ng/L) were measured using an ELISA technique. Sarcopenia was diagnosed based on the 2019 Asian Working Group for Sarcopenia (AWGS) consensus. Elevated myostatin levels were defined as values above the median. Bivariate and multivariate analyses were performed to assess associations between myostatin, cirrhosis severity, and sarcopenia.

RESULTS

The severity of cirrhosis (CTP B and C) was associated with elevated myostatin levels (PR = 2.046; 95% CI: 1.310–3.193; p = 0.002). Bivariate analysis demonstrated that elevated myostatin (PR = 2.178; 95% CI: 1.370–3.461; p < 0.001), CTP B and C (PR = 1.818; 95% CI: 1.223–2.701; p = 0.004), ascites (PR = 1.606; 95% CI: 1.110–2.324; p = 0.034), and malnutrition (PR = 1.806; 95% CI: 1.242–2.626; p = 0.004) were associated with sarcopenia. In multivariate analysis, only elevated serum myostatin remained significantly associated with sarcopenia (AOR = 4.273; 95% CI: 1.557–11.724; p = 0.005).

CONCLUSION

Elevated serum myostatin levels are strongly associated with sarcopenia in patients with liver cirrhosis. Cirrhosis severity is also linked to higher myostatin levels, suggesting a potential role for myostatin-targeted interventions in sarcopenia management.

Myostatin ; Sarcopenia ; Liver Cirrhosis

Introduction: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. Complications such as cystic fibrosis–related diabetes (CFRD) are well recognized. The association between CF and autoimmune thyroid disease, however, is rare and poorly understood. We report a case of CFRD complicated by Graves’ disease. Case: A 22-year-old male was diagnosed with CF at age 5, confirmed by a positive sweat chloride test. Following the diagnosis, lifelong pancreatic enzyme replacement therapy (Creon) was initiated to treat exocrine pancreatic insufficiency. In 2021, he developed type 3c diabetes, attributed to endocrine pancreatic insufficiency, and required regular basal insulin therapy. In early 2024, he developed hypokalemic periodic paralysis with proximal myopathy, despite potassium correction, and was admitted to the hospital. On admission, examination revealed a fine tremor and diffuse bilateral neck swelling. Biochemical evaluation showed thyrotoxicosis with Free T4 of 37 pmol/L and thyroid-stimulating hormone (TSH) <0.01 mIU/L. He started a tapering dose of carbimazole and propranolol. An urgent neck ultrasound showed a heterogeneous thyroid parenchyma with increased vascularity and no nodules. Elevated anti-thyroid peroxidase (anti-thyroid peroxidase, >600 IU/mL) and TSH receptor antibodies (thyrotropin receptor antibody, 2.57 IU/L) confirmed a diagnosis of Graves’ disease. During follow-ups, he had issues with compliance with the antithyroid therapy. However, the latest thyroid function test in February 2026 showed Free T4 of 20.5 pmol/L with suppressed TSH of <0.01 mIU/L. He remains clinically euthyroid throughout the follow-up. Conclusion This case highlights a rare but clinically relevant coexistence. Clinicians managing symptomatic CF patients should vigilantly screen for thyroid dysfunction to ensure early diagnosis and timely intervention. Early recognition and treatment may improve patient outcomes. Further research is needed to clarify the immunological link between CF and autoimmunity.
Cystic Fibrosis ; Graves Disease

Introduction: Intralesional triamcinolone acetonide (TAC) is an accepted management option for paediatric keloid. TAC is a corticosteroid with five times the potency of hydrocortisone and acts by inhibiting fibroblast growth and thus keloid size. Dermatological adverse effects of TAC are common, but repeated high-dose intralesional TAC can cause the rare complication of Cushing syndrome and suppression of the hypothalamic–pituitary–adrenal (HPA) axis. Case: We report the case of an 11-year-old female referred for worsening lower limb striae and low serum cortisol. Prior to referral, intralesional TAC was administered by a general practitioner to a left lower limb keloid which had developed following an orthopedic intervention. A total of five injections were administered over 4 months: a cumulative dose of 150 mg (equivalent to 700 mg hydrocortisone). The last dose was administered 6 months prior to referral. The morning serum cortisol was low (<13.8 nmol/L) with a concomitantly low adrenocorticotropic hormone (ACTH 0.41 pmol/L) level, consistent with suppression of the HPA axis secondary to exogenous steroids. Renin (84.80 mU/L), aldosterone (280.40 pmol/L), testosterone (0.31 nmol/L), estradiol (85.9 pmol/L) and thyroid function were normal. Physiological oral hydrocortisone replacement was promptly commenced, with education on adrenal crisis and sick days while awaiting recovery of the HPA axis. Conclusion This case illustrates the serious complication of Cushing syndrome with secondary HPA axis suppression due to repeated intralesional TAC therapy for paediatric keloid scars. Factors such as appropriate paediatric doses, size of the keloid, site of injection (dermal, not subcutaneous), and frequency of injections should all be given due consideration before using TAC. Clinicians prescribing steroids to children should be aware that suppression of the HPA axis is a very real and life-threatening complication and that steroids should be prescribed judiciously.
Child ; Keloid ; Triamcinolone

BACKGROUND

Hepatitis B virus causes life-threatening chronic liver infection and increases the risk of death from cirrhosis and liver cancer. A three-dose series of universal HBV vaccination initiated from birth is effective against the disease. It is unclear if catch-up vaccination is also effective in those with incomplete or no HBV vaccination.

OBJECTIVE

To review the evidence on the effect of HBV catch-up vaccination on children and adults to decrease HBV-related morbidity.

METHODS

We searched MEDLINE, Cochrane CENTRAL, ChinaXiv, MedRXIV, BioRXIV, Google Scholar, and ongoing and completed trials on USA: https://clinicaltrials.gov/; China: http://www.chictr.org.cn/searchprojen.aspx, and WHO: https://www.who.int/clinical-trials-registry-platform. The last search date was 30 June 2023. We considered experimental or observational studies, meta-analysis/systematic reviews, completed trials and preprints that investigated the efficacy of catch-up HBV immunization in decreasing morbidity from hepatitis B infection including acute and chronic hepatitis B infection, liver cirrhosis, and hepatocellular carcinoma. There was no age and language restriction. Two reviewers independently rated the quality of included studies using Newcastle – Ottawa Quality Assessment Scale for cohort and crosssectional studies. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach was used to determine the certainty of evidence. Data was presented as number (%) for categorical values. Differences between the unvaccinated and vaccinated group was described as relative risk or odds ratio for categorical variables. Data was pooled using Review Manager 5.4.

RESULTS

A total of four observational studies were included, one of which had data in children and adults [two (one with data in adults) studies in children; 3 in adults]. The cross-sectional study was assessed as good quality; and the three cohorts as fair to good. In children, a high certainty evidence study showed that catch up vaccination in 9 to 18 years old decreased risk of HBsAg positivity [RR: 0.09 (0.004, 0.21)], reduced HBV DNA detection [RR: 0.084 (0.026, 0.273)], and increased antiHBs seroconversion [RR: 2.08 (1.84, 2.33)]. The quality of evidence was deemed high based on a large treatment effect. Another low certainty evidence study in Italy showed that HBV mass immunization in 0-10 years old decreased the prevalence of HBsAg anti-HBc and increased anti-HBs seroconversion after vaccination.

In adults, three low certainty evidence studies were included. Two studies showed decreased incidence of acute hepatitis B [OR: 0.08 (0.05, 0.12), I2 = 33%]. Another study demonstrated a decreased prevalence of hepatocellular carcinoma with HBV vaccination with the incidence ratio of vaccinated with chronically infected at 0.04 (0.02, 0.07) showing a large magnitude of benefit for vaccination against HCC when chronic HBV infection is prevented. The studies were deemed to have low quality due to issue of directness and study design.

CONCLUSION

HBV catch-up vaccination in adults is effective in decreasing the prevalence of acute hepatitis B and hepatocellular carcinoma. It likewise decreased the prevalence of HBsAg and anti-HBc, and provided anti-HBs protection in 0 to 18 years.

Human ; Cirrhosis ; Fibrosis

A 40-year-old, gravida 3 para 2 (1-1-0-2), previous primary cesarean section for nonreassuring fetal status, presented at a tertiary hospital for confirmation of cesarean scar pregnancy (CSP). Transvaginal ultrasound confirmed a CSP at 8 2/7 weeks age of gestation with good embryonic cardiac activity, raising concern for early placenta accreta spectrum. A multidisciplinary team composed of an obstetrician, advanced pelvic surgeon, urologist, and anesthesiologist managed the patient. The patient underwent total abdominal hysterectomy with bilateral salpingectomy, as the patient has a completed family size. Before the procedure, she was given cefuroxime as prophylactic antibiotic. Intraoperatively, there were dense adhesions between the posterior bladder wall and the previous cesarean section scar. Inadvertent injury to the bladder wall was incurred during adhesiolysis. Cystorrhaphy was done by a urologist, while the rest of the surgery was unremarkable, with a 450 ml estimated blood loss. The postoperative course was unremarkable. Bladder rest was achieved by maintaining an indwelling Foley catheter, which remained in place upon discharge on postoperative day 3 and was continued for 7 days thereafter. At follow-up, a successful voiding trial was conducted, confirming the return of normal bladder function.

Human ; Female ; Adult: 25-44 Yrs Old ; Cesarean Section ; Salpingectomy ; Hysterectomy ; Fetal Distress ; Placenta Accreta ; Cefuroxime ; Catheters ; Cicatrix

BACKGROUND AND OBJECTIVE

Evidence regarding the impact of performing endoscopy within 12 hours of variceal bleeding (VB) on outcomes is inconclusive, and there is a lack of local data on this topic. This study aimed to determine if the timing of endoscopy is associated with clinical outcomes.

METHODS

This was a single-center retrospective cohort study which included adult cirrhotic patients admitted for VB from January 2016 to September 2022. The primary outcomes were in-hospital and 6-week mortality. Secondary outcomes included 5-day rebleeding, length of hospital stay (LOS), and blood transfusion requirements (BTR). The relationships between timing of endoscopy and outcomes were evaluated using regression analysis.

RESULTS

In 140 patients, 5.7% underwent urgent endoscopy (?12 hours). The overall median door-to-endoscopy time (DET) was 39.4 hours (IQR 20.0-73.4). The overall in-hospital mortality, 6-week mortality, and 5-day rebleeding rates were 12.9%, 11.4%, and 8.6%, respectively, without significant variability at different DET (p >0.05). Prolonged LOS was evident when endoscopy was delayed to >12 hours from admission (3.5 [IQR 2.25-5.75] vs 6 days [IQR 4-9.75], p = 0.021), while BTR was greater starting at endoscopies performed at >24 hours from admission (1 [0-2] vs 2 units [1-3], p = 0.000). Delayed endoscopy was significantly correlated with LOS (Beta 0.316, SE 0.011, p = 0.000) and BTR (Beta 0.214, SE 0.469, p = 0.003), but not with mortality and early rebleeding.

CONCLUSION

Timing of endoscopy may be independent of mortality and early rebleeding. Timely endoscopy may shorten hospitalization and decrease need for blood transfusion. Other factors affecting clinical outcomes may be at play.

Human ; Cirrhosis ; Fibrosis ; Endoscopy

OBJECTIVE: To observe the effects of moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) on the circular RNA of exon 2-5 of the Pan3 gene (circPAN3), forkhead box O3 (FOXO3), and Bcl-2/adenovirus E1B19kDa-interacting protein 3 (BNIP3) in rats with chronic heart failure (CHF), and explore the potential mechanisms of moxibustion in alleviating myocardial fibrosis. METHODS: Ten rats of 60 male SPF-grade SD rats were randomly assigned into a normal group. The remaining rats underwent left anterior descending coronary artery (LAD) ligation to establish the CHF model. Forty successfully modeled rats were randomly divided into a model group, a moxibustion group, a rapamycin (RAPA) group, and a moxibustion+RAPA group, with 10 rats in each group. The moxibustion group received mild moxibustion at bilateral "Feishu" (BL13) and "Xinshu" (BL15), 30 min per session. The RAPA group received intraperitoneal injection of the autophagy activator RAPA (1 mg/kg). The moxibustion+RAPA group first received RAPA injection, followed by mild moxibustion at bilateral "Feishu" (BL13) and "Xinshu" (BL15). All interventions were administered once daily for 4 consecutive weeks. After the intervention, cardiac ultrasound was used to measure ejection fraction (EF) and left ventricular fractional shortening (FS). Serum placental growth factor (PLGF) level was determined by ELISA. Myocardial tissue morphology and collagen volume were assessed using hematoxylin-eosin (HE) staining and Masson's trichrome staining. The expression levels of circPAN3, FOXO3, and BNIP3 mRNA in myocardial tissue were detected by real-time PCR, while FOXO3 and BNIP3 protein expression levels were analyzed by Western blot. RESULTS: Compared with the normal group, the model group exhibited myocardial cell disorder, severe fibrosis, and increased collagen volume (P<0.01), along with significantly decreased EF, FS, and circPAN3 mRNA expression in myocardial tissue (P<0.01), and the serum PLGF level, as well as FOXO3 and BNIP3 mRNA and protein expression in myocardial tissue were increased (P<0.01). Compared with the model group, the moxibustion group showed reduced myocardial fibrosis, decreased collagen volume (P<0.01), increased EF, FS, and circPAN3 mRNA expression in myocardial tissue (P<0.01), and decreased serum PLGF level as well as FOXO3 and BNIP3 mRNA and protein expression in myocardial tissue (P<0.01). Compared with the model group, the RAPA group showed further deterioration in these parameters (P<0.01). Compared with the RAPA group, the moxibustion+RAPA group exhibited alleviation of myocardial fibrosis, reduced collagen volume (P<0.01), increased EF, FS, and circPAN3 mRNA expression in myocardial tissue (P<0.01), and decreased serum PLGF level as well as FOXO3 and BNIP3 mRNA and protein expression in myocardial tissue (P<0.01). CONCLUSION Moxibustion could alleviate myocardial fibrosis in CHF rats, possibly through upregulation of myocardial circPAN3 expression, downregulation of FOXO3 and BNIP3 expression, and inhibition of excessive myocardial autophagy.
Animals ; Moxibustion ; Heart Failure/metabolism* ; Male ; Rats ; Rats, Sprague-Dawley ; Myocardium/pathology* ; RNA, Circular/metabolism* ; Membrane Proteins/metabolism* ; Forkhead Box Protein O3/metabolism* ; Acupuncture Points ; Humans ; Fibrosis/genetics* ; Chronic Disease/therapy* ; Mitochondrial Proteins

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is the predominant form of chronic liver disease worldwide. This study was designed to investigate the proportion and characteristics of MAFLD within the general Chinese population and to identify the contributory risk factors for liver fibrosis among MAFLD individuals. METHODS: The participants were recruited from a cohort undergoing routine health evaluations at the Third Hospital of Hebei Medical University between May 2019 and March 2023. The diagnosis of MAFLD was based on the established clinical practice guidelines. The fibrosis-4 index score (FIB-4) was employed to evaluate hepatic fibrosis, with a FIB-4 score of ≥1.3 indicating significant fibrosis. Binary logistic regression analyses were used to determine risk factors associated with significant hepatic fibrosis in MAFLD. RESULTS: A total of 22,970 participants who underwent comprehensive medical examinations were included in the analysis. The overall proportion of MAFLD was 28.77% (6608/22,970), with 16.87% (1115/6608) of these patients showing significant fibrosis as assessed using FIB-4. Independent risk factors for significant liver fibrosis in MAFLD patients were male (odds ratio [OR] = 0.676, 95% confidence interval [CI]: 0.558-0.821), hepatitis B surface antigen (HBsAg) positivity (OR = 2.611, 95% CI: 1.557-4.379), body mass index ≥23.00 kg/m 2 (OR = 0.632, 95% CI: 0.470-0.851), blood pressure ≥130/85 mmHg (OR = 1.885, 95% CI: 1.564-2.272), and plasma glucose ≥5.6 mmol/L (OR = 1.815, 95% CI: 1.507-2.186) (all P <0.001). CONCLUSIONS The proportion of MAFLD in an urban Chinese population is 28.77%. About 16.87% of MAFLD patients presented with significant liver fibrosis. Independent risk factors for significant liver fibrosis in MAFLD patients should be noticed.
Humans ; Male ; Female ; Liver Cirrhosis/pathology* ; Middle Aged ; Risk Factors ; Adult ; Fatty Liver/pathology* ; Aged ; China/epidemiology* ; Logistic Models ; Urban Population ; East Asian People

Intestinal fibrosis is a major complication of inflammatory bowel disease (IBD), leading to a high incidence of surgical interventions and significant disability. Despite its clinical relevance, no targeted pharmacological therapies are currently available. This review aims to explore the underlying mechanisms driving intestinal fibrosis and address unresolved scientific questions, offering insights into potential future therapeutic strategies. We conducted a literature review using data from PubMed up to October 2024, focusing on studies related to IBD and fibrosis. Intestinal fibrosis results from a complex network involving stromal cells, immune cells, epithelial cells, and the gut microbiota. Chronic inflammation, driven by factors such as dysbiosis, epithelial injury, and immune activation, leads to the production of cytokines like interleukin (IL)-1β, IL-17, and transforming growth factor (TGF)-β. These mediators activate various stromal cell populations, including fibroblasts, pericytes, and smooth muscle cells. The activated stromal cells secrete excessive extracellular matrix components, thereby promoting fibrosis. Additionally, stromal cells influence the immune microenvironment through cytokine production. Future research would focus on elucidating the temporal and spatial relationships between immune cell-driven inflammation and stromal cell-mediated fibrosis. Additionally, investigations are needed to clarify the differentiation origins of excessive extracellular matrix-producing cells, particularly fibroblast activation protein (FAP) + fibroblasts, in the context of intestinal fibrosis. In conclusion, aberrant stromal cell activation, triggered by upstream immune signals, is a key mechanism underlying intestinal fibrosis. Further investigations into immune-stromal cell interactions and stromal cell activation are essential for the development of therapeutic strategies to prevent, alleviate, and potentially reverse fibrosis.
Humans ; Fibrosis/metabolism* ; Inflammatory Bowel Diseases/pathology* ; Animals ; Transforming Growth Factor beta/metabolism* ; Intestines/pathology*