Objective To explore the adverse event signals of children using macrolide drugs （azithromycin, clarithromycin, and erythromycin）, and provide reference for rational medicine use in clinical practice. Methods Data from children under 12 years old were extracted from the US FAERS database spanning from the first quarter of 2004 to the second quarter of 2023. The adverse drug reaction （ADR） signal mining for three macrolide antibiotics was conducted using the Reporting Odds Ratio （ROR） and Bayesian Confidence Propagation Neural Network （BCPNN） methods. Special emphasis was placed on analyzing and contrasting the differences in adverse events among the three drugs. Results A total of 1 615 reports for children under 12 years old were retrieved from the FAERS database, including 1 024 reports of azithromycin, 460 reports of clarithromycin, and 131 reports of erythromycin. Among azithromycin and erythromycin, there were more reports from boys than girls, while for clarithromycin, there were more reports from girls than boys. Oral administration was the most common route of administration for all three drugs. Regarding the outcome of adverse events reported, azithromycin and clarithromycin were primarily associated with other serious adverse events, whereas erythromycin was mainly associated with hospitalization and other serious adverse events. The number of adverse events reported decreased with increasing age, with a higher number of reports in the 0-3 age group. Using the ROR and BCPNN methods for signal detection, 86 signals were identified for azithromycin, 91 for clarithromycin, and 34 for erythromycin. These signals involved 22 System Organ Classes （SOCs）, with azithromycin mainly concentrated in skin and subcutaneous tissue disorders （n=21）, clarithromycin in gastrointestinal disorders （n=15）, and erythromycin in gastrointestinal disorders （n=8）. Twenty-four signals of moderate to high risk were detected, with 13 for azithromycin, 9 for clarithromycin, and 2 for erythromycin. Conclusion The adverse events induced by the three drugs with different risks in different systems. When clinically treating Mycoplasma pneumoniae pneumonia in children, the risk profiles of drugs in different systems should be considered, and personalized dosing should be implemented.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

Objective To evaluate the efficacy and safety of intense pulsed light(IPL)combined with micro-crosslinked hyaluronic acid injected by Shuiguang needle in skin photoaging.Methods Patients with skin photoaging who were treated in Hangzhou Plastic Surgery Hospital from January 2021 to February 2023 were selected.According to the different treatment methods,they were divided into 3 groups:one group was treated with micro-crosslinked hyaluronic acid injected by Shuiguang needle(Shuiguang treatment group),one group was treated with IPL alone[broad band light(BBL)treatment group],and one group was treated with IPL combined with micro-crosslinked hyaluronic acid injected by Shuiguang needle(combined treatment group).The patients were followed up 3 months after treatment.Global scores for photoaging(GSP)were used to evaluate the photoaging degree on the whole face.Global aesthetic improvement scale(GAIS)was used to evaluate the improvement of the overall appearance after treatment.The data of facial wrinkles,texture,pores,brown spots and red areas of patients was collect by using VISIA complexion analysis system.The visual analog scale(VAS)wasused for pain assessment,and adverse effects were recorded.Results GSP score of combined treatment group was lower than that of Shuiguang treatment group and BBL treatment group(P＜0.05).GAIS improvement scores for wrinkles and texture in combined treatment group were higher than those of Shuiguang treatment group and BBL treatment group(P＜0.05),and the GAIS improvement score for pores in combined treatment group was higher than that in BBL treatment group(P＜0.05).The analysis results of VISIA skin test showed that the values of wrinkles and brown spots in combined treatment group after the operation were lower than those in Shuiguang treatment group and BBL treatment group(P＜0.05),and the value of the red area in combined treatment group was lower than that in Shuiguang treatment group(P＜0.05).The effective rates of wrinkle,texture and pore in combined treatment group was 88.2％,94.1％and 94.1％,respectively,higher than those in other two groups.The complications were immediate erythema,acupuncture reaction,and papule,which could be relieved within a few hours.Conclusion IPL combined with micro-crosslinked hyaluronic acid injection in skin photoaging appears to be effective,durable and safety for skin photoaging.

Objective:To explore the value of prenatal three-dimensional ultrasonography（3DUS）in displaying auricular morphotyping and dimensions for predicting congenital aural atresia（CAA）.Methods:A retrospective collection of 227 fetuses who underwent ultrasound scans and retained auricular 3DUS volumes from January 2018 to December 2023 at the First Affiliated Hospital of Sun Yat-sen University was conducted. Fetuses were divided into two groups：a CAA group（52 fetuses，62 auricles）and a non-CAA group（175 fetuses，202 auricles），based on the presence or absence of external auditory canal identified through postnatal examination. According to 3DUS auricular contour and presence or absence of the concha，the auricles were divided into 4 types：type Ⅰ，C-shaped auricle with a concha；type Ⅱ，Irregular auricle with a concha；type Ⅲ，C-shaped auricle without a concha；type Ⅳ，Irregular auricle without a concha. And auricular length（AL）and width（AW）were measured to calculate the product of the auricular length and width（ALW）. Normal reference ranges for ALW from the non-CAA group were developed. Differences of the auricular morphotyping and Z-score of ALW（ALWZ）were compared between the two groups. Receiver operating characteristic（ROC）curves were used to evaluate the diagnostic efficiency of auricular morphotyping，ALWZ and the regression model. A Logistic regression model for CAA based on auricular morphotyping and ALWZ were established.Results:The auricular morphotyping and ALWZ between the two groups were different statistically（both P<0.05）. The AUC of the auricular morphotyping and ALWZ predicting CAA were 0.960（95% CI = 0.923 - 0.997）and 0.975（95% CI = 0.959 - 0.991）individually. Formula for CAA prediction model combining the two indicators（5.379 × morphotyping - 2.386 × ALWZ - Conclusions:The auricular morphotyping and dimensions can effectively predict CAA.

Objective:To develop a deep learning-based artificial intelligence system for assessing image quality in early pregnancy ultrasound，and to evaluate its performance in anatomical structure identification and quality control.Methods:A retrospective study was conducted by collecting 17 910 static ultrasound images of 8 quality-control planes from fetuses at 11 to 13 +6 weeks of gestation who underwent routine first-trimester ultrasound examinations at the First Affiliated Hospital of Sun Yat-sen University from June 2018 to June 2024. The dataset was divided into a training set（12 536 images），a test set（3 582 images），and a validation set（1 792 images）in a 7∶2∶1 ratio to develop a prenatal-screening artificial intelligence system（PSAIS）and to evaluate its performance in the automatic recognition and quality control of standard planes during early pregnancy. The average precision and mean average precision（mAP）were used to measure the model's ability to recognize the anatomical structures on each plane. Intraclass correlation coefficient（ICC）and Kappa statistics were used to assess the consistency between PSAIS and expert-level sonographers in both plane image quality assessment and standardization. The efficiency of PSAIS was also compared to manual quality control. Results:In the test set，the mAP values for recognizing the anatomical structures of the 8 quality-control planes all exceeded 0.800. In the validation set，PSAIS demonstrated moderate to good agreement with two experts in image quality evaluation：the ICC ranged from 0.713 to 0.843 for one expert and 0.678 to 0.788 for the other，while the Kappa values ranged from 0.590 to 0.768 and 0.530 to 0.702，respectively. In terms of plane standardization scoring，PSAIS showed particularly high agreement with expert ratings on the transventricular view（compliance rate 94.6%，Kappa=0.860）and the four-chamber cardiac view with blood flow（compliance rate 94.1%，Kappa=0.778），with agreement above 70% for the remaining planes. Compared with manual quality-control，PSAIS significantly increased processing speed：the total processing time was only 413 seconds，markedly less than the 77 008 seconds and 94 918 seconds required for manual QC（ P<0.001）. Conclusions:The PSAIS system performs well in recognizing and controlling the quality of standard ultrasound planes in early pregnancy，demonstrating high consistency with expert evaluations and significantly improved processing efficiency. It has potential application value in enhancing the quality and efficiency of early pregnancy screening.

Purpose The study aimed to analyze the relationship between MET gene variants and clinicopathologi-cal features in patients with non-small cell lung cancer(NSCLC).Methods Next-generation sequencing technology was used to detect MET gene variants in NSCLC specimens.The association between MET gene variant status and clini-copathological features was then analyzed.Results Among 1 633 cases of NSCLC,the overall MET mutation rate was 4.53％(74/1 633).Variants were mainly observed in male patients,never-smokers,those older than 60 years,ade-nocarcinoma histology,and patients with TNM stage Ⅲ+Ⅳ disease(P＜0.05).MET gene variant status showed no significant assocication with patient age,sex,smoking history,or pathological subtype(P＞0.05),but was statistical-ly correlated with clinical stage and presence of distant metastasis(P＜0.05).The two major variant types were MET exon 14 skipping and MET amplification,which together accounted for 71.62％of all variants.In addition,MET am-plification was positively correlated with EGFR(P=0.003,rs=0.340)and TP53 mutations(P=0.002,rs=0.362),but showed no correlation with KRAS or ALK gene mutations.In contrast,MET exon 14 skipping was nega-tively correlated with EGFR gene mutations(P＜0.001,rs=-0.409),and showed no significant correlation with KRAS,ALK,or TP53 mutations.Conclusion Different types of MET gene variants(amplification,exon 14 skip-ping,fusion,and others)are significantly associated with clinical advanced clinical stage and distant metastasis in NSCLC,but are independent of patient age,sex,smoking history,and pathological subtype.MET amplification fre-quently co-occur with EGFR and TP53 co-mutations.

Objective:To investigate the clinical efficacy of anterolateral thigh free fat flap (hereinafter referred to as fat flap) transplantation with vascular anastomosis for reconstructing facial depressed scars.Methods:This study was a retrospective observational study. Twelve patients (5 males and 7 females, aged 15-67 years) with facial depressed scars who met the inclusion criteria were treated at the First Affiliated Hospital of Air Force Medical University from June 2017 to September 2023. Before surgery, the patient and observer scar assessment scale (POSAS) was used to evaluate the facial scar condition of the patients. Scar depression area was measured ranging from 5 cm×4 cm to 14 cm×7 cm, with a depth from 6 to 12 mm. All cases were reconstructed with fat flaps. The harvested fat flaps ranged 6 cm×5 cm to 15 cm×8 cm in size, with vascular pedicle lengths ranging from 4 to 7 cm. Intraoperatively, the number of perforator vessels observed was as follows: 1 perforator in 2 cases, 2 perforators in 7 cases, and 3 perforators in 3 cases. Fat flaps were transplanted to the recipient sites, with the main trunks of its perforator vessels and accompanying veins anastomosed to the recipient arteries and veins. Donor site wounds were closed primarily. Postoperatively, the survival of fat flap, vascular crisis, and the healing of donor site incision were observed. During follow-up, the facial contour was observed, the long-term reintervention at recipient sites was recorded, and the scars formed at both donor and recipient incisions were observed. The function of donor limb was assessed. At the last follow-up, the scar condition at recipient site was evaluated using the two subscales of POSAS (the observer scale and the patient self-rating scale), respectively.Results:One patient developed a mild hematoma due to bleeding within 24 hours after surgery. After timely removal of the hematoma and enhanced drainage, the fat flap survived. The fat flaps of the other patients survived completely with no vascular crisis occurred. The donor site incision of 1 patient developed infection 7 days after surgery and healed after timely dressing changes, while the donor site incisions of the remaining patients all healed smoothly. During the follow-up of 6-26 months, significant improvement in facial symmetry was observed in all patients, with natural fullness achieved. Autologous microlipofilling was performed in 2 patients at 6 months and 10 months postoperatively, respectively. Local liposuction contouring was conducted in 1 patient at 12 months postoperatively. The scars at the donor and recipient sites were mild. No functional impairment at donor sites was recorded, and the motor and sensory functions of the affected limbs were normal. At the last follow-up, the observer scale assessment showed that the scores for vascularity, thickness, roughness, pliability, pigmentation, and overall assessment of the scars in the recipient areas were 2.1±0.5, 1.9±0.7, 3.0±0.7, 2.1±1.2, 3.8±1.1, and 2.8±0.5, respectively, which were significantly lower than 4.2±0.9, 5.1±1.0, 4.2±1.5, 4.6±1.4, 4.8±1.2, and 5.2±1.0 before surgery (with t values of 7.24, 11.70, 4.31, 9.57, 4.17, and 9.30, respectively, P<0.05). The patient self-rating scale assessment showed that the scores for pain, pruritus, color, stiffness, irregularity, thickness, and overall satisfaction of the scars in the recipient areas were 1.3±0.5, 1.3±0.4, 1.9±1.0, 2.3±1.1, 1.8±0.8, 1.9±0.8, and 1.9±0.7, respectively, which were significantly lower than 2.9±1.0, 2.6±0.9, 4.2±1.5, 5.3±2.0, 4.0±1.2, 4.6±1.3, and 4.8±1.4 before surgery (with t values of 6.09, 5.20, 8.07, 9.17, 8.00, 8.60, and 8.81, respectively, P<0.05). Conclusions:Transplantation of the fat flaps with vascular anastomosis can safely and effectively reconstruct facial depressed scars, and significantly improve the aesthetic contour and scar-related symptoms. This technique yields stable long-term outcomes with high patient satisfaction, demonstrating high value of clinical application.

Objective:To explore the neuropathological characteristics of brain tissues from autopsy of patients with schizophrenia.Methods:Forty-two autopsy cases from National Human Brain Bank for Health and Disease, School of Medicine, Zhejiang University from January 2013 to December 2024 were selected as research subjects, among which, 21 were schizophrenia patients(schizophrenia group) and 21 were non-schizophrenia patients (non-schizophrenia group). Clinical data of patients from the two groups were compared. HE staining was used to detect the pathological changes such as infarction, hemorrhage and arteriosclerosis in the brain tissues, silver-nitrate staining was used to detect the amyloid plaques in the brain tissues, Congo red staining was used to detect the pathological changes related to cerebral amyloid angiopathy (CAA) in the brain tissues, modified Gallyas silver staining was used to detect the neurofibrillary tangles in the brain tissues, and immunohistochemical staining was used to detect the expressions of phosphorylated tau protein, β-amyloid protein (Aβ), TAR DNA binding protein 43 (TDP-43), and α-synuclein in the brain tissues. Alzheimer's disease neuropathologic change (ADNC), primary age-related tauopathy (PART), limbic-predominant age-related TDP-43 encephalopathy (LATE), aging-related tau astrogliopathy (ARTAG), Lewy body disease (LBD), and cerebrovascular disease (CVD)-related pathological changes in the brain tissues were evaluated, and differences in positive rates of the above pathological changes were compared.Results:No significant difference in gender, age of death, brain weight, or apolipoprotein E genotype was noted between the schizophrenia group and non-schizophrenia group ( P>0.05). Six schizophrenia patients exhibited low-to-intermediate ADNC, including 4 with low ADNC and 2 with intermediate ADNC. Compared with the non-schizophrenia group, the positive rates of ADNC- and CVD-related pathological changes in the schizophrenia group were significantly higher (0 vs. 28.6%; 9.5% vs. 47.6%, P<0.05). No significant differences in positive rates of PART-, LATE-, ARTAG-, and LBD-related pathological changes were noted between the schizophrenia group and non-schizophrenia group ( P>0.05). Conclusion:Schizophrenia patients show high proportions of ADNC- and CVD-related pathological changes, but relatively low ADNC severity.

Objective To compare the consistency of voice parameters collected by commonly used smart-phone brands in China and professional recording equipment,and to study whether smartphones can be used for voice research.Methods A total of 67 normal subjects were selected for voice recording using six different smart-phone brands(via the"Active Health"screening APP from the National Key Research and Development Program)and professional recording equipment.Acoustic voice parameters such as fundamental frequency parameters,fre-quency variation parameters,amplitude variation parameters,formant parameters,and energy parameters were ex-tracted from the vowels/a/,/i/,and/u/.A one-way ANOVA test and Tukey's HSD post-hoc comparisons were conducted on the independent variables.Results There were no significant differences between smartphones and professional recording equipment in terms of fundamental frequency parameters such as median F0,mean F0,max F0 and min F0;frequency parameters such as jitter local,jitter local absolute,jitter rap,jitter ppq5,and jitter ddp;amplitude parameters such as shimmer local,shimmer local dB,shimmer apq3,shimmer apq5,shimmer apq11,and shimmer dda;and formant parameters such as F1,F2,F3,and F4.However,significant differences were found in energy parameters such as mean energy(F=31.171,P＜0.001),max energy(F=34.193,P＜0.001),and min energy(F=5.453,P＜0.001)between smartphones and professional recording equipment.Conclusion The smartphones using the"Active Health"screening app from the National Key Research and Development Program can replace professional recording equipment for voice research.However,caution should be exercised when selec-ting energy-related acoustic parameters.