1.The Effect of Banxia Xiexin Decoction (半夏泻心汤) on the Expression of LXRα in Liver Tissue and the JAK2/STAT3 Signaling Pathway in Gastric Antrum Tissue of Diabetic Gastroparesis Model Rats
Qi XU ; Nuobing RUAN ; Jinju LI ; Xijuan LYU ; Zhaohui FANG
Journal of Traditional Chinese Medicine 2025;66(2):178-187
ObjectiveTo explore the potential mechanism of Banxia Xiexin Decoction (半夏泻心汤, BXD) in the treatment of diabetic gastroparesis (DGP). MethodsA total of 29 SD rats were randomly divided into four groups, blank group (5 rats) and model group, BXD group and metformin group (8 rats in each group). Except for the blank group, rats were administered intraperitoneally with 1% streptozotocin (STZ) solution and were fed a high-sugar, high-fat diet to establish the DGP rat model. After successful modeling, the BXD group was treated with BXD at 6.68 g/(kg·d) by gavage, the metformin group was treated with metformin hydrochloride at 105 mg/(kg·d) by gavage, and the blank group and the model group were treated with normal saline at 6.68 ml/(kg·d) by gavage, for 8 weeks. After the last administration, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG) were measured and gastric emptying rate was calculated. ELISA was used to detect the levels of gastrointestinal hormones motilin (MTL) and gastrin (GAS), as well as inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in gastric tissue. Oil red O staining was performed to observe liver pathological morphology. Hematoxylin and eosin (HE) staining was used to observe gastric antrum tissue morphology. Immunofluorescence staining was used to detect liver X receptor α (LXRα) levels in the liver. Western Blot was used to detect the protein levels of LXRα in liver tissue, and of janus kinase 2 (JAK2), phospho-janus kinase 2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3) and phospho-signal transducer and activator of transcription 3 (p-STAT3) in gastric antrum tissue. Quantitative real-time polymerase chain reaction (qPCR) was used to measure the mRNA expression of LXRα in liver tissue and JAK2, STAT3 in gastric antrum tissue. ResultsCompared with the blank group, the model group showed significant hepatic fatty degeneration, gastric antrum tissue structure destruction, and increases in FBG, HbA1c, TC, and TG levels; the average fluorescence intensity, protein level, and mRNA expression of LXRα in liver tissue were reduced; the gastric emptying rate and gastric tissue GAS and MTL levels decreased; inflammatory factors including TNF-α, IL-6, IL-1β in gastric tissue increased, IL-10 decreased; in gastric antrum tissue, the mRNA expression of p-JAK2/JAK2, p-STAT3/STAT3, and JAK2 and STAT3 increased (P<0.01). Compared with the model group, both the BXD group and the metformin group showed improved liver and gastric antrum tissue pathology; FBG, HbA1c, TC, and TG levels decreased, while LXRα fluorescence intensity, protein level, and mRNA expression in liver tissue significantly increased; the gastric emptying rate and the levels of GAS and MTL in gastric tissue were markedly higher; the levels of TNF-α, IL-6, and IL-1β decreased, whereas IL-10 levels increased, p-JAK2/JAK2, p-STAT3/STAT3, and the mRNA expression of JAK2 and STAT3 in gastric antrum tissue decreased (P<0.05 or P<0.01). The BXD group showed higher level than the metformin group in FBG, HbA1c, and TG levels, lower level in gastric emptying rate and gastric tissue GAS content, and higher level in gastric tissue TNF-α, IL-6, IL-1β levels; there was also a decrease in IL-10 levels, and a reduction in LXRα fluorescence intensity and mRNA expression in liver tissue, as well as in p-JAK2/JAK2 levels in gastric antrum tissue (P<0.05 or P<0.01). ConclusionBXD can reduce blood glucose and lipid levels in DGP model rats while improving gastric function and alleviating gastric tissue inflammation. Its mechanism may be related to the regulation of LXRα expression in liver tissue and the JAK2/STAT3 pathway in gastric antrum tissue.
2.Comparison of the clinical efficacy of super pulse thulium laser enucleation of the prostate with "open tunnel" and holmium laser enucleation of the prostate for benign prostatic hyperplasia
Jidong XU ; Ning JIANG ; Jian LI ; Zhikang CAI ; Jianwei LYU ; Chuanyi HU ; Jingcun ZHENG ; Zhonglin CAI ; Huiying CHEN ; Yan GU ; Yuning WANG ; Jiasheng YAN ; Zhong WANG
Journal of Modern Urology 2025;30(1):34-38
[Objective] To compare the clinical efficacy of super pulse thulium laser enucleation of the prostate (SPThuLEP) with "open tunnel" and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH), in order to provide reference for the treatment options of BPH. [Methods] The clinical data of 112 BPH patients treated in our hospital during Jan.2023 and Jul.2023 were retrospectively analyzed, including 65 treated with SPThuLEP with "open tunnel" and 57 with HoLEP.The operation time, postoperative hemoglobin decrease, postoperative bladder irrigation, catheter indwelling time, hospitalization time and complications were compared between the two groups.The changes of maximum urine flow rate (Qmax), international prostate symptom score (IPSS), quality of life score (QoL), postvoid residual (PVR) and prostate-specific antigen (PSA) were compared between the two groups before operation and one month after operation. [Results] All operations were successful without conversion to open or transurethral plasmakinetic resection.The postoperative decrease of hemoglobin in SPThuLEP group was lower than that in HoLEP group [(13.12±6.72) g/L vs. (21.02±6.51) g/L], with statistical difference (P<0.05). There were no significant differences in the operation time [(63.35±15.73) min vs.(61.02±17.55) min], postoperative bladder irrigation time [(1.07±0.45) d vs. (1.06±0.36) d], catheter indwelling time [(2.98±0.56) d vs. (3.01±0.63) d] and hospitalization time [(3.63±0.61) d vs.(3.79±0.76) d] between the two groups (P>0.05). No blood transfusion, secondary bleeding or unplanned hospitalization occurred, and there were no serious complications such as transurethral electroresection syndrome (TURS), urethral stricture and urinary incontinence.One month after operation, the Qmax, IPSS, QoL, PVR and PSA of the two groups were significantly improved compared with those before operation (P<0.05), but with no statistical difference between the two groups (P>0.05). [Conclusion] SPThuLEP with "open tunnel" has comparable efficacy as HoLEP in the treatment of BPH.With advantages of small amount of bleeding and high safety, this minimally invasive technique can be widely popularized in clinical practice.
3.Determination method of plasma concentrations of 7 anti-tumor drugs and its application
Jinxiu LYU ; Nan YAN ; Wenjun XU ; Jing ZHAO ; Hua ZHU ; Pengzhou HANG
China Pharmacy 2025;36(4):475-481
OBJECTIVE To establish a method for simultaneous determination of 7 anti-tumor drugs (irinotecan, capecitabine, paclitaxel, docetaxel, tamoxifen, letrozole and methotrexate) in human plasma and apply it to the clinic. METHODS After precipitating with a methanol-acetonitrile mixture (1∶ 1, V/V) containing 0.1% formic acid, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the plasma concentration, using deuterium isotopes of each analyte as internal standards. The chromatography was performed on the Agilent Eclipse Plus C18 column with a gradient elution of water (containing 0.1% formic acid+0.04% 5 mmol/L ammonium formate) as mobile phase A and acetonitrile (containing 0.1% formic acid) as mobile phase B. The flow rate was 0.6 mL/min, and the column temperature was set at 40 ℃ . The sample size was 10 μL, and the analysis lasted for 5.5 min. Electrospray ionization was used in positive and negative ion mode, and multiple reaction monitoring mode was used. The ion pairs used for quantitative analysis were m/z 587.1→167.1 (irinotecan), m/z 360.1→244.1 (capecitabine), m/z 876.4→308.0 (paclitaxel), m/z 830.3→304.2 (docetaxel), m/z 372.1→129.1 (tamoxifen), m/z 284.1→242.1 (letrozole), and m/z 455.0→ 308.0 (methotrexate). A total of 97 patients with malignant tumors in our hospital were selected to measure the plasma concentrations of 7 anti-tumor drugs using the above method. RESULTS The linear ranges of irinotecan, capecitabine, paclitaxel, docetaxel, tamoxifen, letrozole and methotrexate were 2-1 000 ng/mL (r=0.994 3), 20-10 000 ng/mL (r=0.997 5), 2-1 000 ng/mL (r=0.997 9), 1-500 ng/mL (r=0.995 8), 1-500 ng/mL (r=0.995 2), 1-500 ng/mL (r=0.996 4), 10-5 000 (r=0.997 7), respectively. The quantitative lower limits were 2, 20, 2, 1, 1, 1 and 10 ng/mL; RSDs of intra-assay precision were 0.08%-14.86% (n=6). RSDs of inter-batch precision were 1.51%-11.55% (n=3), and the accuracies were 89.17%-114.93% (n=6). The matrix effects ranged from 89.89%-119.74% (n=6). RSDs of the stability tests were 1.98%-14.88% (n=6). The results of E-mail:hangpengzhou@163.com clinical application showed, the average plasma concentrations of irinotecan, capecitabine, paclitaxel and docetaxel were 704.09, 909.40, 36.45, 150.43 ng/mL, respectively. The values of the coefficient of variation were 25.24%, 62.65%, 122.69%, and 92.27%. CONCLUSIONS The established LC-MS/MS method is simple and rapid, and can be used for the simultaneous determination of 7 commonly used anti-tumor drugs in the plasma of patients with malignancy.
4.Exploring Immune Mechanism of Alveolar Epithelial Homeostasis in Idiopathic Pulmonary Fibrosis Based on Principle of "Spleen being in Charge of Defensive Function"
Jie CHEN ; Lijian PANG ; Ningzi ZANG ; Jingyu WANG ; Siyu LI ; Yuanyu LIANG ; XU XINZHU ; Ping LEI ; Xiaodong LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):259-264
Idiopathic pulmonary fibrosis (IPF) can be classified as pulmonary collateral disease,and its pathogenesis is mainly characterized by the loss of Qi meridian nourishment,the loss of Yin meridian nourishment,and the formation of blood stasis in the blood vessels. Qi Yin deficiency is the pathological basis that runs through IPF,and obstruction of meridians and collaterals is a key element in the development of the disease. The dysfunction of "spleen being in charge of the defensive function" is closely related to the formation of the pathological pattern of "lung deficiency and collateral stasis" in IPF. The term "spleen being in charge of the defensive function" originated from the Yellow Emperor's Inner Canon. If the spleen is healthy,the Qi will be filled with vitality. Positive energy is stored inside,evil cannot be dried up. Its concept is quite similar to the immune defense function in modern medicine. If the principle of "spleen being in charge of the defensive function" is lost,the key structure and function of the IPF alveolar epithelial barrier may be abnormal,and it can interact with various innate immune cells to promote inflammation and fibrosis processes. Therefore,this article explains the imbalance of immune homeostasis in IPF alveolar epithelium from two aspects:the barrier function of alveolar epithelial cells(AECs) and their interaction with innate immune cells. And based on the theory of "spleen being in charge of the defensive function",using traditional Chinese medicine for strengthening the spleen and nourishing Qi to treat IPF from the perspective of the spleen. This not only strengthens the scientific connotation of "spleen being in charge of the defensive function" in the pathogenesis of IPF,but also provides new research directions and ideas for its future clinical prevention and treatment.
5.Organizational Readiness for Change and Factors Influencing the Implementation of Shared Medical Appointment for Diabetes in Primary Healthcare Institutions
Wei YANG ; Yiyuan CAI ; Jiajia CHEN ; Run MAO ; Lang LINGHU ; Sensen LYU ; Dong XU
Medical Journal of Peking Union Medical College Hospital 2025;16(2):479-491
The success of implementation research is closely tied to the institution's pre-implementation readiness. This study aims to explore the organizational readiness for change (ORC) and its influencing factors on primary healthcare settings in the implementation of the "Shared Medical Appointment for Diabetes (SMART) in China: design of an optimization trial" and to enhance ORC and provide insights to support the effective implementation of the program. Qualitative interviews and quantitative surveys were conducted to evaluate the ORC level and its influencing factors in 12 institutions implementing the SMART program. The Scale for Assessing the Institution's Readiness to Implement Evidence-Based Practices was utilized to measure ORC levels. Qualitative interviews were conducted among change implementers to gather information regarding the status of influencing factors. Thematic analysis was applied to extract factors from the interview data, and an assessment questionnaire was developed to measure the perceived impact of these factors. A fuzzy-set qualitative comparative analysis (fsQCA) method was employed to identify the influencing factors of ORC and pathways leading to high-level ORC. Seventy implementers from 12 institutions, encompassing administrators, clinicians, and health managers, participated in the interviews and surveys. The median and interquartile of the ORC scores were 105.20 (101.23, 107.33). The fsQCA indicated that a clear understanding of specific tasks and responsibilities, the active engagement of key participants, sufficient preliminary preparation, and the use of audits and feedback mechanisms were critical pathways to a high-level ORC. Conversely, institutions lacking key participants, preliminary preparation, or marginal influence demonstrated a low-level ORC. Before implementing innovation, Coherence and Cognitive Participation were identified as critical factors in influencing ORC. Strong leadership from key participants played pivotal role in enhancing readiness for change and was essential for improving implementation fidelity and overall program success.
6.Analysis on Quality Standard of Hedyotis Herba Dispensing Granules Based on Standard Decoction
Jinghua ZHANG ; Nana WU ; Yanan LYU ; Guiyun CAO ; Jiacheng XU ; Yongqiang LIN ; Xiaodi DONG ; Jinxin LI ; Zhaoqing MENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):210-217
ObjectiveTo establish the specific chromatogram and quantitative analysis of multi-components by single-marker(QAMS) based on linear calibration using two reference substances(LCTRS), explore the consistency between Hedyotis Herba dispensing granules and standard decoction, and evaluate the quality of the dispensing granules. MethodsHigh performance liquid chromatography(HPLC) specific chromatogram was established based on 15 batches of Hedyotis Herba standard decoction and 10 batches of the dispensing granules, and LCTRS was used to locate chromatographic peaks. The actual retention times of 7 characteristic peaks in the specific chromatogram was measured on 24 different types of C18 columns, taking deacetyl asperulosidic acid and asperulosidic acid as the dual standard compounds, the retention times of the other 5 characteristic peaks were predicted and validated. Based on this, QAMS was developed to determine the contents of four components(deacetyl asperulosidic acid, deacetyl asperulosidic acid methyl ester, asperulosidic acid, and p-coumaric acid). Then, the relative correction factors of deacetyl asperulosidic acid, deacetyl asperulosidic acid methyl ester and p-coumaric acid were calculated using the reference peak of asperulosidic acid in the dual standard compounds, and each component was quantified accordingly. Finally, the consistency between the dispensing granules and standard decoction was assessed by taking extract rate of the standard decoction, consistency of the specific chromatograms, contents and transfer rates of the indicator components as indexes, and the quality of the dispensing granules was evaluated. ResultsThere were 7 common peaks in the characteristic chromatogram of samples of Hedyotis Herba standard decoction and the dispensing granules, and four of them were identified by reference standards, namely deacetyl asperulosidic acid(peak 1), deacetyl asperulosidic acid methyl ester(peak 3), asperulosidic acid(peak 6) and p-coumaric acid(peak 7). The similarity between the dispensing granules and the standard decoction was >0.9. The absolute deviation in the predicted retention time for each component by LCTRS was lower than that of the relative retention time method. The extract rate of the 15 batches of Hedyotis Herba standard decoction ranged from 7.89% to 14.60%, the contents of deacetyl asperulosidic acid, deacetyl asperulosidic acid methyl ester, asperulosidic acid and p-coumaric acid were 6.62-19.70, 3.83-17.99, 1.57-6.69, 1.62-4.52 mg·g-1, and the transfer rates of these components from decoction pieces to the standard decoction were 22.89%-39.60%, 34.03%-62.24%, 24.25%-43.70%, and 40.58%-73.71%, respectively. The extract rate, index component contents and transfer rates from decoction pieces to the three batches of Hedyotis Herba dispensing granules(P1-P3), produced by manufacturer A, were similar to those of the standard decoction prepared from the same batch of decoction pieces, and all fell within the specified range. The contents of the 4 indicator components in 7 batches of the dispensing granules(P4-P10) from manufacturers B-E were all within the range of the content converted from the standard decoction based on the quantity of the dispensing granules. ConclusionThe established specific chromatogram and QAMS based on LCTRS are reasonable and reliable. Based on the evaluation indicators of standard decoction yield, consistency of specific chromatograms, contents and transfer rates of the four index components, the 10 batches of Hedyotis Herba dispensing granules from various manufacturers have exhibited good consistency with the standard decoction, indicating that the current production process is relatively reasonable.
7.Correlation Between Quality of Life and Traditional Chinese Medicine Syndromes in Patients with Myasthenia Gravis
Yibin ZHANG ; Qi LU ; Baitong WANG ; Yixun QI ; Hanying XU ; Peng XU ; Meijin SONG ; Peixi ZHAO ; Zhiguo LYU ; Jian WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):275-281
ObjectiveThis study aimed to explore the correlation between the quality of life (QOL) and different traditional Chinese medicine (TCM) syndromes in patients with myasthenia gravis (MG), identifying potential influencing factors to provide new insights for clinical interventions and improving the QOL of patients with MG. MethodsA questionnaire survey was conducted on 93 adults with MG who visited the Department of Neurology at the Affiliated Hospital of Changchun University of Chinese Medicine from March 2023 to January 2024. Statistical analysis was performed on the clinical data collected using SPSS 24.0 software. ResultsAmong the 93 patients with MG, the average score for myasthenia gravis quality of life-15 (MGQOL-15) was 17.65±6.27, and that for the 36-item short form health survey (SF-36) was (106.13±11.83) scores. The QOL was rated as good for 16 patients and moderate for 77 patients. There were no statistically significant differences in the scores of MGQOL-15, SF-36, and their individual scales by gender or education level. Age showed statistically significant differences in MGQOL-15 and the role physical (RP) scale (P<0.05), and occupational type showed significant differences in the vitality (VT) scale (P<0.01). The Myasthenia Gravis Foundation of America (MGFA) classification had statistical significance on the total SF-36 score (P<0.01), VT scale (P<0.01), role emotional (RE) scale (P<0.05), social functioning (SF) scale (P<0.05), and physical functioning (PF) scale (P<0.01). Among patients with different TCM syndromes, there were significant differences in MGQOL-15 scores (F=4.919, P<0.01). Moreover, significant differences were observed in SF-36 scores (P<0.01), VT scale (P<0.01), RE scale (P<0.05), mental health (MH) scale (P<0.01), and SF scale (P<0.05). ConclusionFactors affecting the QOL of patients with MG include age, occupational type, and clinical classification of MG. Specifically, a greater impact on the QOL of older patients is observed, while physical laborers have a poorer QOL compared to non-physical laborers. Patients classified as MGFA type Ⅱ and higher have a poorer QOL. Additionally, there is a potential correlation between the QOL and TCM syndromes, with patients presenting with spleen and kidney Qi deficiency having a lower QOL than those with spleen and stomach Qi deficiency or Qi and Yin deficiency, which is particularly evident in the VT, RE, MH, and SF scales.
8.Traditional Chinese Medicine Intervention in Diabetic Nephropathy Based on PI3K/Akt Signaling Pathway: A Review
Miao XU ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; You WANG ; Yuzhuo CHANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):90-97
Diabetic nephropathy (DN) is a renal disorder induced by prolonged hyperglycemia, with major pathological features including persistent albuminuria, progressive decline in glomerular filtration rate, and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes, the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment, DN may eventually progress to end-stage renal disease (ESRD). Currently available therapeutic options are often associated with significant adverse effects and high costs, and a large number of patients still progress to ESRD due to delayed treatment. Therefore, there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway plays a critical role in oxidative stress, inflammatory responses, autophagy, and glycolysis, and is closely associated with the pathophysiological progression of DN. In recent years, traditional Chinese medicine (TCM) has achieved remarkable progress in the prevention and treatment of DN, supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target, multi-component, and multi-pathway actions, along with minimal side effects, TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms, the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research, summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers, active constituents, Chinese patent medicines, and herbal compound formulas in the treatment of DN, aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.
9.Traditional Chinese Medicine Intervention in Diabetic Nephropathy Based on PI3K/Akt Signaling Pathway: A Review
Miao XU ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; You WANG ; Yuzhuo CHANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):90-97
Diabetic nephropathy (DN) is a renal disorder induced by prolonged hyperglycemia, with major pathological features including persistent albuminuria, progressive decline in glomerular filtration rate, and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes, the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment, DN may eventually progress to end-stage renal disease (ESRD). Currently available therapeutic options are often associated with significant adverse effects and high costs, and a large number of patients still progress to ESRD due to delayed treatment. Therefore, there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway plays a critical role in oxidative stress, inflammatory responses, autophagy, and glycolysis, and is closely associated with the pathophysiological progression of DN. In recent years, traditional Chinese medicine (TCM) has achieved remarkable progress in the prevention and treatment of DN, supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target, multi-component, and multi-pathway actions, along with minimal side effects, TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms, the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research, summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers, active constituents, Chinese patent medicines, and herbal compound formulas in the treatment of DN, aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.
10.A Case Report of Pachydermoperiostosis by Multidisciplinary Diagnosis and Treatment
Jie ZHANG ; Yan ZHANG ; Li HUO ; Ke LYU ; Tao WANG ; Ze'nan XIA ; Xiao LONG ; Kexin XU ; Nan WU ; Bo YANG ; Weibo XIA ; Rongrong HU ; Limeng CHEN ; Ji LI ; Xia HONG ; Yan ZHANG ; Yagang ZUO
JOURNAL OF RARE DISEASES 2025;4(1):75-82
A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in

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