Objective:To explore the reasonable timing of radiotherapy for epidermal growth factor receptor ( EGFR) mutation-positive non-small cell lung cancer patients with brain metastasis in the era of third-generation targeted drugs. Methods:Clinical data of EGFR mutation-positive non-small cell lung cancer patients with brain metastasis who received first-line treatment with third-generation targeted drugs and stereotactic radiotherapy at Shanghai Armed Police Corps Hospital from September 2019 to May 2022 were retrospectively analyzed. According to the timing of radiotherapy before / after targeted drug resistance, all patients were divided into the early and salvage radiotherapy groups. The proportion of brain metastasis, physical fitness, complete response rate, objective response rate, delaying the progression of brain metastasis and overall survival (OS) were compared between two groups. Kaplan-Meier method was used for survival analysis, log-rank test was used for univariate prognostic analysis, and factors with P <0.1 were included in Cox multivariate analysis. Results:A total of 85 patients were included, including 51 (60%) cases receiving early radiotherapy. Patients who participated in early radiotherapy had a higher proportion of symptomatic brain metastasis (82% vs. 56%, P=0.013) and poorer physical fitness (Kanofsky performance score <70: 61% vs. 26%, P=0.002) compared to patients who underwent salvage radiotherapy. Early radiotherapy significantly improved the complete response rate of intracranial lesions (35% vs. 12%, P=0.015) and objective response rate (88% vs. 71%, P=0.041), delayed the progression of brain metastasis (median intracranial progression free survival: 23.0 months vs. 16.0 months, P=0.005; median intracranial secondary progression free survival: 31.0 months vs. 22.0 months, P=0.021), and improved OS (median OS: 44.0 months vs. 35.0 months, P=0.046). In multivariate analysis, diagnosis-specific graded prognostic assessment score <2.5, mutation of EGFR exon 21, and salvage brain radiotherapy were adverse prognostic factors for OS. Conclusion:In the era of third-generation targeted drugs therapy, early involvement of stereotactic radiotherapy in non-small cell lung cancer patients with brain metastasis can bring greater clinical benefits.

Ferroptosis is a novel type of oxidatively regulated cell death driven by iron-dependent lipid peroxidation.As the main site of iron utilization and oxidative metabolism,mitochondria are the main source of intracellular reactive oxy-gen species.Ferroptosis is associated with the severe impairment of mitochondrial structure and function,bioenergetics,and metabolism.Alzheimer disease(AD)is a devastating progressive neurodegenerative disease with the main clinical manifestation of decline in memory and cognitive function.Emerging evidence suggests that mitochondrial dysfunction plays a significant role in the process of ferroptosis in AD.This article elaborates on the mechanism of ferroptosis,mito-chondrial dysfunction and its role in ferroptosis in AD,and the treatment of AD,in order to provide a new perspective for exploring new strategies for the prevention and treatment of AD.

Objective:To investigate the coverage of qualified iodized salt in catering service units where residents ate out in Shanxi Province, so as to provide a basis for taking targeted preventive measures timely and adjusting of intervention strategies scientifically, and to consolidate the achievements of eliminating iodine deficiency disorders (IDD) continuously.Methods:One prefecture level city from each of the five directions of east, west, south, north and middle in Shanxi Province in 2021 was selected. One mountainous county and one plain county were selected in each city. Each of the counties was divided into five sampled regions along five different geographic directions: east, west, south, north and middle. From each region, one town/street was selected randomly and then two canteens of enterprises and institutions (canteens), five medium-sized restaurants and five small restaurants were selected from each town/street. We investigated the basic information of catering service units, collected salt samples and then detected the iodine content of these salt samples. In addition, salt iodine testing data of county residents corresponding to catering service units in the 2021 iodine deficiency disorders monitoring were collected from the Shanxi Institute of Endemic Disease Prevention and Treatment, and compared with the survey results of catering service units.Results:A total of 660 salt samples were detected, the median value of salt iodine was 27.65 mg/kg, the coverage rate of iodized salt was 99.39%(656/660), and the coverage rate of qualified iodized salt was 90.76% (599/660). The median value of salt iodine was 26.70, 28.00 and 27.60 mg/kg in canteens, medium-sized restaurants and small restaurants, respectively, and the coverage rate of qualified iodized salt was 95.54% (107/112), 90.42% (236/261), and 89.20% (256/287), respectively. There was no significant difference in the coverage rate of qualified iodized salt among different types of catering service units (χ 2 = 3.92, P = 0.141). The median value of salt iodine was 28.00 and 27.20 mg/kg in mountainous counties and plain counties, respectively, and the coverage rate of qualified iodized salt was 88.67% (266/300) and 92.50% (333/360), respectively. There was no significant difference in the coverage rate of qualified iodized salt among the counties of different geographical types (χ 2 = 2.87, P = 0.090). The median value of salt iodine in catering service units and households was 27.65 and 23.50 mg/kg, respectively, and the coverage rate of qualified iodized salt was 90.76% and 95.91%, respectively. There was a statistically significant difference in the coverage rate of qualified iodized salt between catering service units and households (χ 2 = 31.19, P < 0.001). Conclusions:The coverage rate of qualified iodized salt in catering service units in Shanxi Province generally meets the national elimination standard (> 90%), but there are still some counties that do not meet the standard. The coverage rate of qualified iodized salt in small and medium-sized restaurants is also not optimistic. It is recommended to strengthen monitoring and supervision of edible salt in catering service units in the future.

Objective:To investigate the current situation of water-borne high iodine hazards in Shanxi Province and the implementation of prevention and control measures, providing a scientific basis for prevention and control of the high iodine hazards in the future.Methods:In 2020, a survey was conducted on iodine content of drinking water and water improvement situation in all high iodine administrative villages in 12 water-borne high iodine counties of 4 cities in Shanxi Province. In each monitoring county, five administrative villages were selected as monitoring villages using a systematic sampling method, sorted by the iodine content of the water in the administrative villages. Forty non-boarding students aged 8 - 10 from one primary school and 20 pregnant women were selected from each monitoring village. Household edible salt samples and one random urine sample were collected for salt iodine and urinary iodine content test. B-ultrasound method was used for thyroid examination in children.Results:A total of 297 high iodine administrative villages were surveyed on the drinking water situation of residents, including 268 villages with improved water and 29 villages without improved water, with a water improvement rate of 90.24%. The range of water iodine was 0.33 - 803.75 μg/L, and there were 159 villages with water iodine content > 100 μg/L. A total of 1 926 samples of household edible salt were tested, and the rate of non iodized salt was 62.20% (1 198/1 926); 1 704 urine samples from children and 222 urine samples from pregnant women were tested, with median urinary iodine contents of 426.2 and 318.9 μg/L, respectively. The 1 690 cases of thyroid gland in children were examined, with a goiter rate of 3.91% (66/1 690) and a nodule detection rate of 13.67% (231/1 690).Conclusions:Children's iodine nutrition in water-borne high iodine areas of Shanxi Province is at an iodine excess level, while pregnant women's iodine nutrition is at an iodine excess level. Efforts should be made to increase the popularization of non iodized salt and improve water quality to reduce iodine in areas with high iodine levels, in order to control the harm of high iodine in water sources as soon as possible.

Objective:To investigate the serum 25-hydroxyvitamin D [25(OH)D] level in patients with Graves' disease (GD) and its correlation with thyrotropin receptor antibody (TRAb) and bone metabolism markers.Methods:A total of 124 patients with newly diagnosed or relapsed GD were selected and divided into three groups according to serum 25(OH)D level, namely vitamin D deficiency group with 25(OH)D <12 μg/L, vitamin D insufficiency group with 25(OH)D of 12 to 20 μg/L, and vitamin D sufficiency group with 25(OH)D ≥ 20 μg/L. The levels of serum 25(OH)D, TRAb, type I procollagen N-terminal pro-peptide (PINP), type I collagen cross-linked C-terminal peptide (S-CTX), parathyroid hormone (PTH), total triiodothyronine (TT 3), total thyroxine (TT 4) and thyroid-stimulating hormone (TSH) were measured in all patients, and the differences of these biochemical indices were compared across groups. Oneway analysis of variance or Kruskal-Wallis test was used for comparison between groups, and Pearson or Spearman correlation analysis was applied for correlation test. Results:The levels of serum TT 3, TT 4, PINP, and S-CTX significantly increased ( P < 0.01) and the level of phosphorus (P) decreased ( P < 0.01) with the decreased vitamin D levels. The levels of PTH and calcium (Ca) were significantly lower in the vitamin D sufficiency group compared with the vitamin D insufficiency group and vitamin D deficiency group ( P < 0.01). Correlation analysis showed that serum 25(OH)D level was negatively correlated with the levels of TT 3, TT 4, PINP, S-CTX, PTH and Ca ( P < 0.01), and positively correlated with the levels of P and TSH ( P < 0.01). Conclusions:Decreased serum 25(OH)D level is closely related with increased bone turnover, PTH, and thyroid hormone levels in patients with GD, but not related with TRAb. Thyroid hormone levels have a certain predictive value regarding vitamin D deficiency in GD patients. It is necessary to monitor the vitamin D levels in patients with GD and provide vitamin D supplementation to reduce the incidence of osteoporosis, improve the effectiveness of antithyroid treatment and reduce the recurrence of GD.

Objective:To investigate the surgical method and clinical effect of O-arm navigation mini-open burring for osteoid osteoma.Methods:Eighteen patients with osteoid osteoma were treated with O-arm guided grinding drill from June 2021 to May 2022, including 15 males and 3 females, the age was (18.4 ±10.9) years (range 2 to 44 years), and the course of disease ranged from 1 week to 3 years (mean 14.2 months). The lesions sites included 6 cases of proximal femur, 3 cases of distal femur, 4 cases of proximal tibia, 1 case of distal tibia, 2 cases of proximal fibula and 1 case of distal and proximal humerus. During the operation, the O-arm navigation was used to determine the location of the focus, the muscle and soft tissue was peeled off to the bone surface through a 1-4 cm small incision, the channel retractor was placed, and the burr was registered as a navigation recognition device to gradually remove the bone on the surface of the tumor nest, and the tumor nest was scraped with a curette for pathological examination; according to the navigation image, the focus was enlarged removed with burr and the grinding range was confirmed by the O-arm X-ray machine before the end of the operation. The patients were followed up for 6 to 15 months (mean 9.5 months). CT scans were performed before and after surgery for imaging comparison in order to figure out whether it had residual lesions or recurrence. The visual analogue score (VAS) of pain was used as a parameter for evaluating the clinical efficacy.Results:The operation time of 18 cases was 40-175 min, with an average of 89.3 min. The time required to establish navigation image was 18.0 ±4.1 min (range 13 ~ 22 min). The length of the incision was 2.7±1.1 cm (range 1-4 cm). All patients achieved complete curettage of the lesions, and osteoid osteoma was confirmed by pathology after operation. All the patients could move to the ground 24 hours after operation, and the pain was significantly relieved from 3 to 7 d after operation, and the pain almost disappeared 3 months after operation. The VAS score of 18 cases was 5.33±1.24 before surgery, 2.79±1.32 on the 3rd day, 1.86±1.21 on the 7th day, 0.86±0.93 on the 1st month, 0.33±0.48 on the 3rd month, and 0.09±0.29 on the 6th month after operation, and the difference was statistically significant ( F=58.50, P<0.001). There were no serious complications during and after operation, and the success rate of treatment (no recurrence of symptoms, no residual recurrence of imaging lesions, no serious complications after operation) was 100%. Conclusion:Treatment of osteoid osteoma with mini-open excision using burrs under the navigation of O-arm is a simple, safe, minimally invasive and efficient technique. Intraoperative precise positioning and the use of burr with navigation to remove a larger area than the tumor nest are the keys to successful treatment.

Objective:To explore the risk factors of recurrence after resection of thigh soft tissue malignant tumors and the evaluation of the postoperative lower limb function.Methods:A total of 211 patients who underwent thigh soft tissue malignant tumor resection in the Department of Orthopaedics of the second affiliated Hospital of Medical College of Zhejiang University from May 2011 to May 2021 were retrospectively analyzed, including 117 males and 94 females, aged 53 (43, 65) years. There were 59 cases of atypical/well-differentiated liposarcoma, 30 cases of other types of liposarcoma, 33 cases of malignant fibrous histiocytoma, 19 cases of fibrosarcoma, 12 cases of rhabdomyosarcoma, 12 cases of leiomyosarcoma, 9 cases of synovial sarcoma, and 37 cases of others. The tumor involvement of muscle, bone, blood vessel, nerve tissue and intermuscular compartment, postoperative Musculoskeletal Tumor Society (MSTS) functional score and recurrence were recorded. The relationship between anatomical structure and postoperative recurrence was analyzed by Cox logistic regression to determine risk factors; the cumulative recurrence rate of different compartment groups (medial compartment, anterior compartment, and posterior compartment) were compared; The Box plot was used to compare the postoperative function of patients with resection of different anatomical structures (e.g., vastus lateralis, biceps femoris, femur, etc.).Results:A total of 34 out of 211 patients relapsed, with a recurrence rate of 16.1%. The recurrence time ranged from 2.6 months to 91.6 months after operation, with a median recurrence time of 37.0 (18.2, 52.8) months. Three independent risk factors were found to be associated with recurrence, namely: pathological grade [ HR=3.86, 95% CI(1.75, 8.51)], involvement of vastus intermedius [ HR=3.05, 95% CI(1.53, 6.06)], and involvement of vastus medialis [ HR=3.17, 95% CI(1.56, 6.41)]. The recurrence rate of patients with anterior chamber tumor resection was 35.3%, which was higher than that of patients without tumor resection (16.2%), and the difference was statistically significant ( P=0.020). There was no significant difference in recurrence rate between patients with medial chamber tumor resection and patients without tumor resection ( P>0.05). The recurrence rate of patients with posterior compartment tumor resection was 12.3%, which was lower than that of unresectable patients (37.6%), and the difference was statistically significant ( P=0.002).The postoperative MSTS score of 167 patients averaged 26±3.2 points (9-30 points). After intraoperative resection of part of the femur, vastus intermedius, vastus medialis, and rectus femoris, the patient's function was relatively poor [corresponding median MSTS score: 25 (23, 28), 26 (24 28), 26 (24,28), 26(24, 27)]. Conclusion:The risk factors for local recurrence after resection of thigh soft tissue malignant tumors include: pathological grade of the tumor, and whether the vastus intermedius or vastus medialis is involved. Anterior compartment tumors have a higher recurrence rate after surgery. If the tumor involves the above-mentioned anatomical structures, more attention should be paid to the risk of local recurrence after surgery.

Objective:To explore the value of 5G-based robotic remote ultrasound diagnosis system in musculoskeletal joint injuries.Methods:From March to December 2020, 58 volunteers at a training base who felt musculoskeletal pain or paresthesia were selected and performed both robotic remote ultrasound (remote ultrasound group) and conventional ultrasound (portable ultrasound group). The two types of examinations were compared, the consistency of the two diagnosis results was analyzed by the Kappa test, and the the difference of the diagnosis results was compared by McNemar test.Results:Among the 58 volunteers, 40 cases were positive by both methods and 11 volunteers had 2-3 positive results. There were 59 positive results in the remote ultrasound group and 64 positive results in the portable ultrasound group. The positive rate of the examination sites from high to low was knee joint>foot and ankle joint >hand and wrist joint >shoulder joint>elbow joint, calf and hip. The diagnosis results of the two groups were in good consistency (Kappa=0.782, P<0.001), and there was no statistically significant difference in the diagnosis results between the two groups (χ 2=3.2, P=0.063). Five more diseases with positive results were detected in the portable ultrasound group: 1 meniscus injury, 1 medial collateral ligament injury, 1 soft tissue injury around the metatarsal, 1 biceps tendinitis with effusion and 1 cubital ulnar nerve subluxation. Conclusions:The 5G-based robotic remote ultrasound system has good consistency with conventional ultrasound in the diagnosis of musculoskeletal injures. It can be applied to the ultrasound diagnosis of musculoskeletal joint injuries in remote areas.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

Objective: To study dose-response relationships of fractionated irradiation induced pulmonary fibrosis in mice according to radiological imaging changes of lung. Methods: A total of 8-10 week old-female C57BL6 mice were randomized into different groups for whole thoracic irradiation. The prescribed doses were 0, 2.0, 4.0, 6.0, 7.0, 8.5 Gy per fraction in a total of 5 fractions. CT imaging was performed at 24 weeks post irradiation. The averaged lung density and volume changes were obtained by the three-dimensional segmentation algorithm, and further analyzed in Boltzmann regression modeling. Results: At the endpoint of 24 weeks, the dose-dependent pulmonary radiological alternations were revealed by coronal view of CT images. Translational analysis of fibrosis-related gene-signatures as well as histological collagen stainings further corroborated the radiological findings. According to Boltzmann modeling, the E₅₀ of radiation-induced lung density changes was found to be (30.80±0.80)Gy (adjusted R²=0.97); whereas the E₅₀ for radiation-induced lung volume reduction was determined as (31.31±7.07)Gy (adjusted R²=0.92). Both outcomes indicated a remarkable enhancement of tolerance to normal lung tissues after exposure with 5-fraction versus single fraction scheme. Conclusions The radiation-induced lung density and volume changes depend not only on total dose, but also the number and dose of fractions.