Objective:To investigate the effect of repetitive transcranial magnetic stimulation(rTMS)on sleep structure and quality in children with autism spectrum disorder(ASD).Methods:Sixty children with ASD who met the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)criteria were randomly assigned to rTMS treatment group and pseudo-treatment group.The rTMS group received bilateral low-frequency(0.5 Hz)stimulation,and the pseudo-treatment group received pseudo-stimulation at the same time and place.Sleep quality and autism symptoms were assessed at baseline,midpoint(15 sessions),and endpoint(30 sessions),using the Childhood Sleep Disorders Scale(SDSC)and the Behavior Rating Scale for Children with Autism Spectrum Disorders(ABC)before treatment,15 times and 30 times of intervention,and statistical analysis was performed.Results:There was no significant difference in SDSC factor and total score between the two groups before treatment(P＞0.05).After 15 and 30 treatments,the total scores of SDSC and all factors were lower in the rTMS group than in the pseudo-treatment group(P＜0.05).Repeated measurement ANOVA found that there was an interaction be-tween the groups and the number of interventions,that is,the scores of the two groups had different downward trends,and the decline of the treatment group was more obvious than that of the pseudo-treatment group.There was no significant difference in the interaction between ABC scale scores and intervention times(P＞0.05).Conclu-sion:Repetitive transcranial magnetic stimulation significantly improves the sleep structure and quality in children with autism spectrum disorder.

Objective:To investigate the effect of repetitive transcranial magnetic stimulation(rTMS)on sleep structure and quality in children with autism spectrum disorder(ASD).Methods:Sixty children with ASD who met the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)criteria were randomly assigned to rTMS treatment group and pseudo-treatment group.The rTMS group received bilateral low-frequency(0.5 Hz)stimulation,and the pseudo-treatment group received pseudo-stimulation at the same time and place.Sleep quality and autism symptoms were assessed at baseline,midpoint(15 sessions),and endpoint(30 sessions),using the Childhood Sleep Disorders Scale(SDSC)and the Behavior Rating Scale for Children with Autism Spectrum Disorders(ABC)before treatment,15 times and 30 times of intervention,and statistical analysis was performed.Results:There was no significant difference in SDSC factor and total score between the two groups before treatment(P＞0.05).After 15 and 30 treatments,the total scores of SDSC and all factors were lower in the rTMS group than in the pseudo-treatment group(P＜0.05).Repeated measurement ANOVA found that there was an interaction be-tween the groups and the number of interventions,that is,the scores of the two groups had different downward trends,and the decline of the treatment group was more obvious than that of the pseudo-treatment group.There was no significant difference in the interaction between ABC scale scores and intervention times(P＞0.05).Conclu-sion:Repetitive transcranial magnetic stimulation significantly improves the sleep structure and quality in children with autism spectrum disorder.

Objective:To investigate the value of flattening filter-free (FFF) mode in postoperative deep inspiration breath-hold (DIBH) intensigy-modulated radiotherapy for left breast cancer.Methods:A retrospective case series study was conducted. Clinical data of 21 patients with left breast cancer who underwent DIBH intensity-modulated radiotherapy after modified radical surgery in Meizhou People's Hospital from January 2021 to December 2022 were retrospectively analyzed. On the DIBH-mode CT of each patient, the 7-field intensity-modulation plan was designed using the plan developed in the 6 MV FFF-mode (FFF group) or the plan developed in the 6 MV flattening filter (FF)-mode (FF group). The target areas and organs at risk, dosimetric and biological parameters, and dose validation results were compared between the two plans.Results:Twenty-one patients were female with the age [ M ( Q1, Q3)] of 47 years old (32 years old, 61 years old). The percentage of target areas receiving 95% of the prescribed dose (V 95%) was (95.9±0.8)% and (95.7±1.9)% in the FF and FFF groups ( t = 2.98, P = 0.089), and the maximum dose was (5 401±251) cGy and (5 424±201) cGy ( t = 2.85, P = 0.181), the fitness indices were 0.88±0.05 and 0.87±0.06 ( t = 0.32, P = 0.562), the homogeneity indices were 1.06±0.01 and 1.07±0.02 ( t = 2.91, P = 0.009), the equivalent uniform doses (EUD) were (51.81±0.21) Gy and (51.97±0.20) Gy ( t = 0.51, P = 0.309), and the tumor control probability (TCP) was (99.68±0.01)% and (99.61±0.02)% ( t = 0.81, P = 0.560). The plans of the FFF group and the FF group were compliant, and the doses of all organs at risk to be irradiated were within the clinically acceptable range, and the radiation doses in the FFF group in the left lung [5 Gy irradiated volume (V 5 Gy), mean dose (D mean), EUD and normal tissue complication rate (NTCP)], right lung (V 5 Gy and D mean), heart (V 10 Gy, D mean, EUD and NTCP), and right breast (V 5 Gy, D mean and EUD) were differently lower than those in the FF group, and the differences were statistically significant (all P < 0.05). The monitor units in the FFF and FF groups were (984±132) MU and (751±145) MU ( t = -1.25, P < 0.001), and the total beam-on time was (1.4±0.3) min and (2.2±0.4) min ( t = 0.68, P < 0.001); individual field beam-on time was (12±7) s and (16±10) s ( t = 2.68, P = 0.001), and the beam-on time for each field in patients of the FFF group was less than 25 s; γ pass rates were (97.1±2.8)% and (97.6±2.1)% ( t = 0.59, P = 0.484). Conclusions:In the intensity-modulated radiotherapy of left breast cancer, the radiation dose of the energy to the critical organs in FFF mode is lower and has higher dose rate and shorter treatment time. FFF combined with DIBH technique has positive clinical significance in the intensity-modulated radiotherapy of breast cancer.

BACKGROUND: Epidemiological studies have demonstrated a causal relationship between ambient ozone (O 3 ) and mortality from chronic obstructive pulmonary disease (COPD), which is the only outcome considered in the Global Burden of Disease Study 2021 for O 3 . This study aims to evaluate the temporal trend and spatial distribution of the COPD burden attributable to O 3 across China from 1990 to 2021. METHODS: The ambient O 3 concentrations in China were estimated. Based on the methodology framework and standard analytical methods applied in the Global Burden of Disease Study 2021, we estimated the annual number, age-standardized rate, and percentage of deaths and disability-adjusted life-years (DALYs) from COPD attributable to O 3 pollution during 1990-2021 at the national and provincial levels in China. RESULTS: In 2021, a total of 125.7 (95% uncertainty interval [UI], 26.4-228.3) thousand deaths and 1917.5 (95% UI, 398.7-3504.6) thousand DALYs from COPD were attributable to ambient O 3 pollution in China, accounting for 9.8% (95% UI, 2.1-17.0%) and 8.1% (95% UI, 1.8-14.1%) of the total COPD deaths and DALYs, respectively. Generally, a higher burden was observed among males, the elderly, and the population residing in regions with worse health conditions. The age-standardized rates of COPD deaths and DALYs per 100,000 populations ranged from 0.5 (95% UI, 0-1.4) and 8.1 (95% UI, 0.7-20.9) in Hong Kong to 22.8 (95% UI, 3.9-43.5) and 396.6 (95% UI, 68.9-763.7) in Xizang. From 1990 to 2021, there was a notable decrease in the age-standardized rates of COPD-related deaths (68.2%, 95% UI, 60.1-74.9%) and DALYs (71.5%, 95% UI, 63.7-77.6%), especially in regions with poor health conditions. However, the attributable numbers and percentages changed relatively marginally. CONCLUSIONS Ambient O 3 pollution is a major contributor to the COPD burden in China. Our findings highlight the significant spatial heterogeneity across different provinces and underscore the implementation of geographically tailored policies to effectively reduce O 3 pollution and alleviate the associated disease burden.
Pulmonary Disease, Chronic Obstructive/etiology* ; Ozone/analysis* ; Humans ; China/epidemiology* ; Global Burden of Disease ; Male ; Air Pollution/adverse effects* ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Disability-Adjusted Life Years ; Quality-Adjusted Life Years

Objective To study the antifungal activity of a new series of triazole compounds with n-propyl side chain and disubstituted benzyl structure. Methods Eleven target compounds were designed and synthesized. The structures were confirmed by ¹H NMR, and some compounds were confirmed by ¹³C NMR or HRMS. Three fungal strains were selected as experimental strains, and the antifungal activity was tested in vitro according to the standardized antifungal sensitivity test method recommended by National Committee for Clinical Laboratory Standards (NCCLS). Results Compound B11 showed better activity against candida albicans SC5314 than fluconazole and was comparable to posaconazole; Compounds B10, B11 and B4 showed better activity against cryptococcus neoformanis H99 than fluconazole, while compounds B2, B3, B5, B6 and B7 showed similar activity to fluconazole against cryptococcus neoformanis H99; while all compounds showed poor activity against aspergillus fumigatus. Conclusion Some of the target compounds with n-propyl side chain and disubstituted benzyl group structure had certain antifungal activity and could be identified as potential lead antifungal drugs.

Both natural ginsenoside F2 and unnatural ginsenoside 3β,20S-Di-O-Glc-DM were reported to exhibit anti-tumor activity. Traditional approaches for producing them rely on direct extraction from Panax ginseng, enzymatic catalysis or chemical synthesis, all of which result in low yield and high cost. Metabolic engineering of microbes has been recognized as a green and sustainable biotechnology to produce natural and unnatural products. Hence we engineered the complete biosynthetic pathways of F2 and 3β,20S-Di-O-Glc-DM in Saccharomyces cerevisiae via the CRISPR/Cas9 system. The titers of F2 and 3β,20S-Di-O-Glc-DM were increased from 1.2 to 21.0 mg/L and from 82.0 to 346.1 mg/L at shake flask level, respectively, by multistep metabolic engineering strategies. Additionally, pharmacological evaluation showed that both F2 and 3β,20S-Di-O-Glc-DM exhibited anti-pancreatic cancer activity and the activity of 3β,20S-Di-O-Glc-DM was even better. Furthermore, the titer of 3β,20S-Di-O-Glc-DM reached 2.6 g/L by fed-batch fermentation in a 3 L bioreactor. To our knowledge, this is the first report on demonstrating the anti-pancreatic cancer activity of F2 and 3β,20S-Di-O-Glc-DM, and achieving their de novo biosynthesis by the engineered yeasts. Our work presents an alternative approach to produce F2 and 3β,20S-Di-O-Glc-DM from renewable biomass, which lays a foundation for drug research and development.

Traumatic rib fractures are the most common injury in thoracic trauma. Previously，the patients with traumatic rib fractures were mostly treated non-surgically，of which 50%，especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities，being unable to retain a full-time job. In the past two decades，thanks to the development of internal fixation material technology，the surgical treatment of rib fractures has achieved good outcomes. However，there are still some problems in clinical treatment，including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans，and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore，the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association，in conjunction with national multidisciplinary experts，formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures（2021）following the principle of evidence-based medicine，scientific nature and practicality. This expert consensus puts forward some clear，applicable，and graded recommendations from aspects of preoperative imaging evaluation，surgical indications，timing of surgery，surgical methods，rib fracture sites for surgical fixation，internal fixation methods and material selections，treatment of combined injuries in rib fractures，in order to provide references for surgical treatment of traumatic rib fractures.

Objective:To introduce a surgical technique of implant-based immediate breast reconstruction using the "latent orifice" procedure after skin-sparing mastectomy and to investigate the clinical value of this procedure.Methods:Clinical data of 72 patients who underwent immediate breast reconstruction using the "latent orifice" procedure (we placed the silicone prosthesis in a "latent orifice" consisting of fascia and underlying muscles) from Jan. 2016 to Dec. 2019 were collected. Characteristics of surgical technique and the effect of the reconstruction surgery were analyzed.Results:70 patients underwent nipple-areola complex sparing mastectomy (NSM) . Two patients’ nipples were resected due to intraoperative frozen pathology suggesting carcinoma existing in the nipples. The nipple epidermal necrosis occurred in 3 patients. No seroma, incision infection or capsular contracture occurred. According to the evaluation scale, the overall aesthetic score was 9.39 points. The average score of each subscale was: 9.57 points for breast volume, 9.43 for breast contour, 9.84 for placement of implant, 9.38 for scars, 9.27 for lower pole projection and 9.21 for inframammary fold definition. BREAST-Q questionnaires were filled by patients. Scores of psychosocial well-being ranged from 62 to 93 points, with the median score of 77 points. Satisfaction with breasts scores ranged from 58 to 100 points, with the median score of 71 points.Conclusion:The "latent orifice" procedure is a simple, safe, practicable, aesthetic and satisfying type of immediate implant-based breast reconstruction, which is worth practicing and promoting.

Objective To develop a diagnostic model based on deep neural network for intelligent discrimination of thyroid function. Methods A total of 1616 patients ( 283 males, 1333 females, average age:52 years) who underwent thyroid imaging between May 2016 and June 2018 were selected. According to the clinical diagnosis, the 1616 cases included 299 normal thyroid cases, 876 hyperthyroidism cases and 441 hypothyroidism cases. Feature extraction and learning training were performed on 1000 training set sam-ples by two deep neural network models ( AlexNet;deep convolution generative adversarial networks ( DCGAN) ) using deep learning algorithm. Performance verifications were implemented on 616 test set samples. The con-sistency between the verification results of the two models and the clinical diagnosis was analyzed by Kappa test. Meanwhile, the time advantage of the intelligent diagnosis models was analyzed. Results The average diagnostic time of AlexNet model was 1 s/case, and the classification accuracy for normal thyroid, hyperthy-roidism, hypothyroidism were 82.29％(79/96), 94.62％(369/390), 100％(130/130), respectively. The Kappa value between results of AlexNet model and clinical diagnosis was 0.886 ( P<0.05) . The average di-agnostic time of DCGAN model was 1 s/case, and the classification accuracy for normal thyroid, hyperthy-roidism, hypothyroidism were 85.42％(82/96), 95.64％(373/390), 99.23％(129/130), respectively. The Kappa value between results of DCGAN model and clinical diagnosis was 0.904 ( P<0.05) . Conclusion The deep neural network intelligent diagnosis model can quickly determine the functional status of thyroid gland in thyroid imaging, and it has a high recognition accuracy, thus providing a new method for thyroid image review.

OBJECTIVETo observe the effect difference of warming needling combined with decoction and ciloprost for arteriosclerosis obliterans (ASO) with stasis.

METHODSA total of 96 ASO patients with stasis were randomly assigned into a combination group and a western medication group, 48 cases in each group. Anti-hypertension, glucose-lowering and lipid lowering therapies were applied in the two groups. Ciloprost was prescribed orally in the western medication group, twice a day, 100 mg a time. The main acupoints in the combination group were Sanyinjiao (SP 6), Yinlingquan (SP 9), Zusanli (ST 36), Guanyuan (CV 4), and Xuehai (SP 10), matched with Yanglingquan (GB 34) and Weizhong (BL 40). Warming needling was used at Sanyinjiao (SP 6), Zusanli (ST 36), Xuehai (SP 10) and Guanyuan (CV 4), 5 times a week, once a day, 20 min a time. At the same time, self-made decoction was applied in the combination group, 1 dose a day, twice a day. All the treatment was given for continuous 3 courses, 1 month as a course. The indexes were the symptom scores for cool limb skin, sour swelling, numbness, pain, abnormal complexion, ankle brachial index (ABI) and blood biochemical indexes, including fasting blood-glucose (FPG), triacylglycerol (TG), cholesterol total (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminase (AST), serum creatinine (Scr) and blood urea nitrogen (BUN). The adverse reactions were recorded. The clinical effect was evaluated. Two-month follow-up was carried out.

RESULTSAfter treatment, the symptom scores for cool limb skin, sour swelling, numbness, pain, abnormal complexion and total score decreased in the two groups (all <0.05), with better results in the combination group (all <0.05). The bilateral ABI were higher than those before treatment in the two groups (all <0.05), with better results in the combination group (both <0.05). The FPG, TG, TC, HDL-C, LDL-C, ALT, AST, Scr, BUN before and after treatment had no statistical significance in the two groups (all >0.05). There was no adverse reaction on acupuncture and moxibustion. The total effective rate of the combination group was 95.8% (46/48), which was better than 91.7% (44/48) of the western medication group (<0.05). The recurrence and aggravation rate in the combination group was 8.7% (4/46), which was lower than 18.2% (8/44) in the western medication group (<0.05).

CONCLUSIONWarming needling combined with decoction for ASO are better than simple oral ciloprost, with safety.