Objective:To assess the feasibility and efficacy of hypofractionated radiotherapy with simultaneous integrated boost (HFRT-SIB) for patients with non-osteogenic spinal metastases who were not suitable for stereotactic body radiotherapy (SBRT).Methods:A totoal of 26 spinal metastatic lesions in 24 patients with non-osteogenic spinal metastases admitted to Beijing Luhe Hospital affiliated to Capital Medical University from March 2020 to April 2023 were retrospectively analyzed. In our institution, a higher-dose fractionated regimen for spinal metastases was introduced, at a dose of 3 Gy/f ×10 times (5 times a week, once a day) to the clinical target volume (CTV), and simultaneous integrated boost (SIB) of 4 Gy/f ×10 times (5 times a week, once a day) to the gross tumor volume (GTV). The primary endpoint was the overall relief (OR) rates of pain at 12 and 24 weeks post-radiotherapy, while secondary endpoints included the pain response time and duration of pain relief, the incidence of adverse events post-radiotherapy, and the 1-year overall survival (OS) rate. The differences before and after treatment were analyzed by Wilcoxon signed-rank test. OS was assessed using Kaplan-Meier method.Results:The median follow-up was 11.7 (8.0, 17.0) months. At 12 weeks post-radiotherapy, 92% (22/24) of patients achieved OR, and 81% (17/21) obtained OR at 24 weeks post-radiotherapy. The median pain response time was 4 (3, 5) d. At the last follow-up, 42% (10/24) of patients maintained pain relief for over 1 year, with a median duration of pain relief up to 11.0 (6.0, 16.9) months. The 1-year OS rate was 66.3%, and no patients experienced grade 3 or higher acute or chronic adverse events.Conclusion:HFRT-SIB can effectively alleviate pain, and achieve sustained pain control, and does not lead to severe adverse effects in patients with non-osteogenic spinal metastases.

Objective:To investigate the clinical, epidemic and laboratory characteristics of brucellosis in Hainan, and to summarize the experience of diagnosis and treatment.Methods:The epidemiological characteristics, clinical manifestations, laboratory results, treatment and prognosis of 27 inpatients with brucellosis admitted to the Second Affiliated Hospital of Hainan Medical University from January 2019 to December 2023 were retrospectively analyzed.Results:In 27 cases, the male to female ratio was 2.38 ∶ 1.00 (19 ∶ 8). Occupational distribution was dominated by farmers and herdsmen, with a total of 21 cases (77.8%). Twenty-one patients (77.8%) had a clear history of contact with cattle, sheep, and related products, and there was a phenomenon of family clustering. Eighteen patients (66.7%) developed symptoms from March to July. The clinical manifestations of the patients were lack of specificity, mainly fever (24 cases, 88.9%), dizziness and headache (13 cases, 48.1%), and low back pain (11 cases, 40.7%). Some patients also had symptoms and signs such as fatigue (8 cases), muscle pain (6 cases), chest tightness (4 cases), and splenomegaly (6 cases). Complications commonly included pulmonary infection (13 cases, 48.1%) and spinal involvement (11 cases, 40.7%). The positive rates of Brucella blood culture, tube agglutination test, Rose Bengal plate agglutination test, and cerebrospinal fluid or joint cavity effusion culture were 76.9% (20/26), 100.0% (21/21), 100.0% (11/11), and 3/4, respectively. The combination therapy of doxycycline and rifampicin showed good therapeutic effects, and 22 patients were cured. Conclusions:Hainan is not an epidemic area of brucellosis, and the clinical manifestations of the disease are not specific. The epidemic and clinical characteristics of the disease should be paid attention to in order to improve the level of diagnosis and treatment and control effectiveness.

Objective To investigate the clinicopathological features,immunophenotypes,molecular genetic alterations,and prognosis of succinate dehydrogenase-deficient renal cell carcinoma(SDH-RCC).Methods A total of 11 cases of SDH-RCC diagnosed at West China Hospital,Sichuan University between 2016 and 2023 were selected for clinicopathological,immunohistochemical,and DNA sequencing analyses.Results Among the 11 cases of SDH-RCC,there were 5 male patients and 6 female patients.The patients'ages ranged from 12 to 71 years,with an average age of 39.7 years.Among them,5 patients had tumors located in the right kidney,5 had tumors located in the left kidney,and 1 patient had bilateral tumors.Microscopic observation showed that the tumor cells of the SDH-RCC patients displayed a wide spectrum of structures,forming sheet-like,nested,and glandular structures.In addition,tumor cells in papillary structures were observed in some cases.The tumor cells had abundant cytoplasm,was eosinophilic,and contained flocculent materials.Intracytoplasmic vacuolations were observed in some of the cells.Among all the patients,7(7/11,63.6％)showed typical low-grade features(grade 1-2 according to the International Society of Urological Pathology[ISUPJ/WHO 2016 classification),and 4(4/11,36.4％)showed high-grade features(grade 3 according to the ISUP/WHO 2016 classification).The average ages of patients with low-grade and high-grade features were 32.1 years and 58.0 years,respectively.Immunohistochemical staining of all 11 cases demonstrated negative results for SDHB and cytokeratin 7(CK7),and positive staining results for paired box 8(PAX-8),fumarate hydratase(FH),and epithelial membrane antigen(EMA).Their Ki-67 index was l％-30％.In one case,the loss of SDHB expression was also accompanied by a loss of SDHA expression.Sanger sequencing was performed to examine all the exons of SDHB in 7 cases.One case showed a frameshift mutation,c.236Tdel(p.K80Rfs*),and another case harbored a missense mutation,c.725G＞A(p.Arg242His).In another case,next generation sequencing revealed that large fragments of SDHB(Exon 4-8 del)were missing.Follow-up data were available for 10 patients.The follow-up time ranged from 4 to 138 months,with the average being 32.8 months,and all patients survived.Metastasis and recurrence were reported in 5 cases,with 3 of them showing high-grade features and 2 showing low-grade features.Conclusion SDH-RCC is rare and the patients demonstrate a relatively young age of onsets.Patients may present with bilateral tumors.Tumors with low-grade features usually occur in young patients,with their Ki-67 index usually being lower than 5％.Individual cases may experience tumor recurrence and metastasis over a long period of follow-up.Tumors with high-grade features tend to occur in older patients who have a higher Ki-67 index,and who are prone to recurrence and metastasis.Negative immunohistochemical staining results for SDHB can assist in tumor diagnosis,but the loss of SDHB protein expression does not necessarily lead to the detection of SDHB gene mutation.

Objective:To investigate the clinical, epidemic and laboratory characteristics of brucellosis in Hainan, and to summarize the experience of diagnosis and treatment.Methods:The epidemiological characteristics, clinical manifestations, laboratory results, treatment and prognosis of 27 inpatients with brucellosis admitted to the Second Affiliated Hospital of Hainan Medical University from January 2019 to December 2023 were retrospectively analyzed.Results:In 27 cases, the male to female ratio was 2.38 ∶ 1.00 (19 ∶ 8). Occupational distribution was dominated by farmers and herdsmen, with a total of 21 cases (77.8%). Twenty-one patients (77.8%) had a clear history of contact with cattle, sheep, and related products, and there was a phenomenon of family clustering. Eighteen patients (66.7%) developed symptoms from March to July. The clinical manifestations of the patients were lack of specificity, mainly fever (24 cases, 88.9%), dizziness and headache (13 cases, 48.1%), and low back pain (11 cases, 40.7%). Some patients also had symptoms and signs such as fatigue (8 cases), muscle pain (6 cases), chest tightness (4 cases), and splenomegaly (6 cases). Complications commonly included pulmonary infection (13 cases, 48.1%) and spinal involvement (11 cases, 40.7%). The positive rates of Brucella blood culture, tube agglutination test, Rose Bengal plate agglutination test, and cerebrospinal fluid or joint cavity effusion culture were 76.9% (20/26), 100.0% (21/21), 100.0% (11/11), and 3/4, respectively. The combination therapy of doxycycline and rifampicin showed good therapeutic effects, and 22 patients were cured. Conclusions:Hainan is not an epidemic area of brucellosis, and the clinical manifestations of the disease are not specific. The epidemic and clinical characteristics of the disease should be paid attention to in order to improve the level of diagnosis and treatment and control effectiveness.

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Humans ; Parkinson Disease/diagnosis* ; Machine Learning

Objective:To study the clinicopathological features, immunophenotype, molecular genetic characteristics and prognosis of renal cell carcinoma associated with TFEB gene rearrangement (TFEBr-RCC).Methods:Eight cases of TFEBr-RCC diagnosed at the West China Hospital of Sichuan University from 2014 to 2022 were collected for clinicopathological, immunohistochemical, fluorescence in situ hybridization and RNA sequencing analyses, with review of literature.Results:Six patients were male and two were female. The patient ages ranged from 25 to 50 years (mean: 34 years, median: 32 years). The tumors were present in the right kidney (3 cases) or the left kidney (5 cases). The maximum diameters of the tumors ranged from 4.0 cm to 18.5 cm, with an average of 8.5 cm. Histologically, majority of the cases (5/8) showed typical biphasic "pseudorosette" structure, while the remaining three cases demonstrated atypical morphology that was similar to epithelioid angiomyolipoma or clear cell renal cell carcinoma. Immunohistochemical study showed positivity of TFEB (8/8), PAX8 (8/8), MART-1 (7/7), and HMB45 (5/6). Interestingly, PD-L1 was variably expressed in all five tested cases. Staining for TFE3 in all cases was negative. TFEB translocation was verified in all 8 cases using TFEB fluorescence in situ hybridization. RNA sequencing showed MALAT1-TFEB gene fusion in 4 of the 5 tested cases (two of which showing novel MALAT1-TFEB fusion sites), and one case with a novel ACTB-TFEB gene fusion. Patient follow-ups ranged from 5 to 96 months (average 47 months). All patients were alive without recurrence or metastasis.Conclusions:TFEBr-RCC tends to occur in young adults and has a good prognosis. Histologically, most of the cases show characteristic biphasic structure, and some cases show epithelioid angiomyolipoma-like or clear cell RCC-like morphology. Immunohistochemical reactivity to TFEB, melanocytic markers and PD-L1 is characteristic. MALAT1-TFEB gene fusion is the most common molecular change, with variable fusion sites.

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Dactinomycin/adverse effects* ; Female ; Gestational Trophoblastic Disease/drug therapy* ; Humans ; Methotrexate/therapeutic use* ; Pregnancy ; Retrospective Studies

Objective:To observe the changes of macular visual function after myopic foveoschisis (MF) and pars plana vitrectomy (PPV) combined with internal limiting membrane peeling and air filling.Methods:A single-center, retrospective study. From October 2018 to October 2019, 29 MF inpatients (32 eyes) in Tianjin Eye Hospital were included in this study. There were 3 males (4 eyes) and 26 females (28 eyes). The age was 63.00±3.45 years old. Equivalent spherical lens degree was -14.16±2.54 D, and axial length was 29.14±1.04 mm. Among them, 3 patients (3 eyes) had lamellar macular holes. All eyes underwent standard pars plana three-channel 25G PPV combined with internal limiting membrane peeling and air filling. Before surgery and at 1, 3, and 6 months after surgery, macular microperimetry was performed with a macular integrity assessment instrument, and the mean retinal sensitivitie (MS) within 10° of the macula, fovea 2° and 4° fixation rates (P1, P2), 63% and 95% bivariate contour ellipse area (BCEA) were recorded. The comparison of MS, P1, P2, 63%BCEA and 95%BCEA at different times before and after surgery was performed by paired t test; the comparison of fixation stability rate was performed by χ 2 test. Results:Compared with before surgery, there were significant differences in the improvement of MS in affected eyes at 1, 3 and 6 months after surgery ( t=-2.208, -3.435,-4.919; P=0.038, 0.002, 0.000). In the pairwise comparison at different times after surgery, only 6 months after surgery and 1 month after surgery were significantly different ( P=0.036). Compared with the preoperative P1, P2, 63%BCEA and 95%BCEA, the P1 and P2 of the eyes gradually increased after surgery, while the 63%BCEA and 95%BCEA gradually decreased, however, the difference was not statistically significant (P1: t=-1.595,-1.698,-1.966; P=0.125, 0.104, 0.062. P2: t=-1.622,-1.654,-1.707; P=0.119, 0.112, 0.102. 63%BCEA: t=1.410, 1.409, 1.553; P=0.172, 0.173, 0.135. 95%BCEA: t=1.412, 1.408, 1.564; P=0.172, 0.173, 0.132). Six months after surgery, all the eyes underwent anatomical repositioning of the macular area, and no serious complications such as full-thickness macular hole and macular hole retinal detachment were found. Conclusions:PPV with internal limiting membrane peeling and air filling is an effective and safe method for MF, and the macular function improved significantly within 6 months postoperatively.

Comorbidities will inevitably lead to an increase in the number of medications used and adverse drug reaction events in elderly patients.Therefore, it is urgent to implement precision medicine in the elderly population.pharmacogenomic testing can increase the opportunity of individualized drug selection for elderly patients, reduce the risk of adverse drug reactions, reduce the cost-effectiveness ratio of medication, improve elderly patients' medication compliance, and thus reduce their readmission rate.Therefore, it is necessary to promote pharmacogenetic testing for elderly patients with comorbidities and polypharmacy, so as to provide measures for the implementation of personalized medicine in the elderly.