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 SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient′s nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 μmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5?147 μmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 μmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.

Objective:To explore the efficacy and adverse effects of 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) in patients with neuroendocrine neoplasms (NEN). Methods:From 2019 to June 2021, 36 patients (26 males, 10 females; age (43.5±12.9) years) with metastatic NEN who were treated with 177Lu-DOTATATE in the Affiliated Hospital of Southwest Medical University were retrospectively analyzed. Toxicities were assessed by using the common terminology criteria for adverse events (CTCAE) version 5.0. Disease progression and tumor response were determined according to the response evaluation criteria in solid tumors (RECIST) version 1.1. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed by Cox proportional-hazards model. Results:Of 36 patients, the median follow-up time was 19.8 months, the median PFS was 24 months, and the median OS was not reached. The WHO grade Ⅲ (hazard ratio ( HR)=3.59, 95% CI: 1.10-11.73, P=0.025; OS: HR=7.85, 95% CI: 1.50-41.10, P=0.004), 18F-FDG positive (PFS: HR=3.05, 95% CI: 1.04-8.93, P=0.033; OS: HR=5.90, 95% CI: 1.04-33.49, P=0.025), and received systemic chemotherapy before peptide receptor radionuclide therapy (PRRT) (PFS: HR=2.79, 95% CI: 1.01-7.73, P=0.039; OS: HR=5.56, 95% CI: 1.01-30.57, P=0.026) were prognostic factors for PFS and OS. Transient side effects included fatigue (27.8%, 10/36), nausea (5.6%, 2/36), and the most common laboratory toxicities were lymphocytopenia (11.1%, 4/36), followed by mild renal toxicity (8.3%, 3/36) and mild liver injury (5.6%, 2/36). Conclusions:PRRT with 177Lu-DOTATATE is an effective and well-tolerated treatment in patients with NEN. PFS and OS are shorter in patients who are WHO grade Ⅲ NEN, 18F-FDG positive, and received systemic chemotherapy before PRRT.

Objective To investigate the awareness of the Radiation Shielding Requirements for Radiotherapy Room–Part 2: Radiotherapy Room of Electron Linear Accelerators (GBZ/T 201.2—2011) among relevant practitioners in medical institutions as well as its implementation and application situation and collect relevant problems and suggestions for an evaluation of the scientificalness, standardization, and timeliness of the standard, and to provide a scientific basis for the further revision and implementation of the standard. Methods An online questionnaire survey was conducted among relevant employees in medical institutions providing medical linear accelerator radiotherapy across 22 provinces of China, which investigated the awareness, training, application, and revision suggestions related to GBZ/T 201.2—2011. The questionnaires were collected and analyzed. Results A total of 340 relevant practitioners filled out the questionnaire. Of the participants, 66.80% were physicists; 79.11% had an awareness of the standard; 56.18% ever participated in the standard-related training; but the survey results showed that the practitioners did not have a good knowledge of the standard’s content, and the training and promotion were not enough; 83.24% thought that the standard had been widely used; 17.60% thought that the standard needed to be revised; 76.76% thought that there was a need to add calculation examples; 88.82% thought that neutron shielding needed to be considered for the 10 MV X-ray accelerator room. Conclusion The standard has been widely known in the field of radiotherapy protection. With the development of radiotherapy technology, the standard should be revised to add calculation examples and consider neutron shielding in the 10 MV X-ray accelerator room. The standard is highly technical and difficult to grasp, so the promotion and implementation goals should be appropriate for different personnel groups, the training for employees at key posts should be strengthened, and the methods recommended in the standard should be uniformly used throughout the country.

ObjectiveTo explore psychological and behavioral characteristics of children with autism spectrum disorder (ASD) using Psycho-educational Profile (Third Edition) (PEP3). MethodsFrom October, 2021 to October, 2022, 192 children with ASD without intervention in the Binzhou Medical University Hospital were selected as observation group, and 96 healthy children who visited at the same time were selected as control group. They were assessed with PEP3. ResultsThe development of receptive language significantly delayed behind expressive language (t = 5.383, P < 0.001) in the observation group. The cognitive, expressive language, receptive language, fine motor, gross motor, imitation and personal self-care correlated with age (r = 0.540 to 0.795, P < 0.001). The Cronbach's α of PEP3 for the observation group was 0.810 to 0.947. The original score of each subtest of PEP3 was less in the observation group than in the control group (|t| > 4.267, P < 0.001). ConclusionThe development of receptive language retards behind the expressive language in children with ASD. Cognitive and motor functions develop with age, while the correlation between maladaptive behavior and age is weak. PEP3 is reliable in internal consistency, and valid in discrimination.

Objective:To analyze the clinical and pathological characteristics, treatment and prognosis of renal changes in patients with Kimura disease and improve the clinicians′ understanding on renal manifestations of Kimura disease.Methods:The clinical data of Kimura disease patients with definite diagnosis and detailed data in Peking Union Medical College Hospital from January 1980 to August 2020 were retrospectively analyzed. The patients were divided into renal impairment group and non-renal impairment group according to whether the kidney was involved or not and the related clinical data between the two groups were compared. The patients presenting with nephrotic syndrome were followed up.Results:There were 60 patients with Kimura disease confirmed by pathological diagnosis with 48 males. The median age was 33(3, 62) years old, and the median duration was 36(12, 111) months. There were 18 cases complicated with renal injury in 49 patients with complete routine urine and renal function examination and the main manifestations of renal injury were proteinuria and/or microscopic hematuria. There was no significant difference at age, sex and absolute value of eosinophils between the two groups (all P>0.05). Compared with the renal inpairment group, patients in non-renal inpairment group had longer course of disease, higher levels of hypersensitive C-reactive protein and erythrocyte sedimentation rate, and lower median values of total eosinophils and total IgE, but there was no statistically significant difference (all P>0.05). Among the patients with renal involvement, 6 patients met the diagnostic criteria for nephrotic syndrome, and 5 of them completed renal biopsies. The renal pathological diagnosis was membranous nephropathy in 2 cases and minimal change disease in 3 cases, and no interstitial eosinophil infiltration was found in renal biopsy tissues. These patients had a good response to glucocorticoids and/or immunosuppressive therapy, and achieved complete remission of nephrotic syndrome; at the same time, lymphadenopathy caused by Kimura disease could be well controlled. Conclusions:Kimura disease can combine with various renal lesions, and the pathology of nephrotic syndrome can be membranous nephropathy or minimal change nephropathy. After energetic treatment of glucocorticoids and/or immunosuppressive therapy, nephrotic syndrome can be completely relieved, and lymphadenopathy can be well controlled. The relationship between Kimura disease and renal disease needs further study.

A young female patient presented with fever, arthralgia, and rash was diagnosed with adults still's disease. When treated with glucocorticoid steroid, the above patient progressed to anuria, sudden, and confusion. After a teamwork involving different departments, the patient was finally diagnosed with atypical hemolytic uremic syndrome (aHUS) and treated with good outcome. aHUS is a rare disease, while Eculizumab is an orphan drug. The diagnosis and treatment of the patient reveals the importance of multidisciplinary team on the diagnosis and treatment of rare and difficult diseases.

Objective:To investigate the antitumor effect of shikonin loaded milk derived exosomes on hepatoma cells.Methods:The experimental study was conducted. Exosomes were isolated from milk by differential centrifugation and be loaded by shikonin to constructed a nano drug loading system. The shikonin content of this nano drug loading system was determined and calculated by spectrophotometry. The cytotoxicity of shikonin loaded milk derived exosomes was evaluated by sulfonyl rhodamine B colorimetry and cell apoptosis was determined by annexin V-FITC/propidium iodide assay. Western blotting was used to detect the Bax and Bcl-2 protein expression level in hepatoma cells. Human HepG2 hepatoma cells treated with shikonin were set as the shikonin treated group and human HepG2 hepatoma cells treated with shikonin loaded milk derived exosomes were set as the shikonin loaded milk derived exosomes treated group. Observa-tion indictors: (1) the loading percentage of shikonin in shikonin loaded milk derived exosomes; (2) the cytotoxicity of shikonin loaded milk derived exosomes on human HepG2 hepatoma cells; (3) cell apoptosis of human HepG2 hepatoma cells; (4) Bax and Bcl-2 protein expression level in human HepG2 hepatoma cells. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups were analyzed using the t test. Results:(1) The loading percentage of shikonin in shikonin loaded milk derived exosomes: the loading percentage of shikonin in shikonin loaded milk derived exosomes was 22.8%. (2) The cytotoxicity of shikonin loaded milk derived exosomes on human HepG2 hepatoma cells: the survival rates of hepatoma cells were 53.9%±2.9% and 45.4%±1.9% in the shikonin treated group and the shikonin loaded milk derived exosomes treated group, respectively, showing a significant difference ( t=46.27, P<0.05). (3) Cell apoptosis of human HepG2 hepatoma cells: the early apoptosis rates of hepatoma cells were 11.3%±1.5% and 14.8%±2.2% in the shikonin treated group and the shikonin loaded milk derived exosomes treated group, respectively, showing no significant difference ( t=1.37, P>0.05). The late and overall apoptosis rates of hepatoma cells were 32.3%±1.3% and 43.6%±4.3% in the shikonin treated group, versus 38.7%±3.2% and 53.5%±4.4% in the shikonin loaded milk derived exosomes treated group, showing significant differences ( t=37.39, 30.97, P<0.05). (4) Bax and Bcl-2 protein expression level in human HepG2 hepatoma cells: Bax and Bcl-2 protein expre-ssion level were 232.0±2.6 and 32.0±1.6 in the shikonin treated group, versus 286.0±3.8 and 17.0±1.5 in the shikonin loaded milk derived exosomes treated group, showing significant differences ( t=69.83, 53.32, P<0.05). Conclusion:The shikonin loaded milk derived exosomes have cytotoxic and apoptosis inducing effects on human HepG2 hepatoma cells, which can inhibit the growth of hepatoma cells.