To investigate the mutations of NF1 and clinical phenotypes in patients with sporadic neurofibromatosis type 1 (NF1). This is aimed to evaluate the efficacy of high-throughput sequencing in diagnosing atypical cases, to expand the mutational spectrum of NF1, and to provide early diagnosis of NF1. Clinical data from 11 sporadic NF1 patients without family history treated at the Fifth Affiliated Hospital of Sun Yat-sen University (2019-2023) were collected. The mutations of NF1 gene were detected using whole-exome sequencing or chip-capture high-throughput sequencing, followed by bioinformatics analysis. Novel mutations were screened against normal population databases to exclude benign polymorphisms, and pathogenicity of the mutations was classified according to ACMG guidelines. The results showed that two novel frameshift mutations were identified: c.7904del (p.Asp2635Valfs*9) and c.5122_5123del (p.Phe1708Hisfs*9). The patient carrying c.7904del exhibited an undocumented phenotype of posterior medullary ischemic degeneration. Among the 11 NF1 patients, the types of mutations included frameshift (4/11), nonsense (3/11), intronic (2/11), splicing (1/11), and start codon variants (1/11). Common phenotypes were cafe-au-lait macules (8/11) and neurofibromas (6/11), yet significant phenotypic heterogeneity existed among patients sharing identical mutations. In conclusion, this study discovered two novel NF1 mutations and an unreported phenotype, expanding both the NF1 mutational spectra and highlights the need for attention to cerebrovascular status in patients carrying NF1 mutations. High-throughput sequencing significantly enhances molecular diagnostic efficacy for atypical NF1, providing a critical basis for clinical NF1 diagnosis.

Objective:To investigate the clinical results of gasless endoscopic thyroidectomy via posterior chest-collarbone approach (GETPCA) compared with open neck surgery for papillary thyroid carcinoma (PTC) .Mthods:Retrospective analysis of PTC patients admitted to the Department of Thyroid and Breast Surgery of the Third Affiliated Hospital of Anhui Medical University from Jan. 2022 to Dec. 2023,and randomly divided into the open group and the lumbo-scopic group according to whether or not they had a requirement for an unmarked neck, in which the open group was n=100,and the lumbo-scopic group was n=67,with 39 male cases and 128 female cases. Clinicopathological characteristics, surgery-related indexes, postoperative complications, postoperative pain scores and postoperative cosmetic satisfaction were compared between the two groups.The t-test,Wilcoxon rank-sum test, χ2 test, consecutively corrected χ2 test, or Fisher’s exact probability method were used to compare the groups. Results:No recurrence was seen during the follow-up period,and none of the cases in the luminal group was open in the middle. The differences in age, body mass index BMI, gender, relative tumor location,preoperative TSH, T stage and N stage between the two groups were not statistically significant ( P>0.05) . The total operation time [ (121.07±39.80) min vs. (93.87±26.97) min]in the luminal group was greater than that in the open group,intraoperative bleeding was less than that in the open group, and the postoperative drainage flow[ (130.69±31.01) mL vs. (105.52±32.71) mL] was greater than that in the open group in the postoperative period of 72 h, and the difference was statistically significant ( P<0.001) .There was no statistical difference between the two groups in terms of 24-h postoperative drainage volume, number of central zone lymph node dissection, number of positive central zone lymph nodes,postoperative hospitalization days or total hospitalization cost ( P>0.05) .The number of cases of neck discomfort (3 cases vs.23 cases, P<0.001) and swallowing dysfunction (2 cases vs.20 cases, P=0.003) in the luminal group was smaller than that in the open group,and the difference was statistically significant.The difference in the incidence of bleeding,incision infection,seroma,temporary recurrent laryngeal nerve injury and temporary parathyroid gland injury between the two groups was also not statistically significant ( P>0.05) .The postoperative NRS on day 1 and postoperative NRS on day 3 of the luminal group were lower than those of the open group,and the difference was statistically significant ( P>0.05) ,while there was no statistically significant difference between the postoperative NRS on day 7,the postoperative NRS on month 1 and the postoperative NRS on month 3 ( P>0.05) .Cosmetic satisfaction at 6 months postoperatively was higher in the luminal group than in the open group,and the difference was statistically significant ( P<0.001) . Conclusion:GETPCA for the treatment of the PTC is safe and feasible,with satisfactory cosmetic results and reduction of neck discomfort and swallowing dysfunction,which is worthy of clinical popularization.

Objective:To investigate the clinical results of gasless endoscopic thyroidectomy via posterior chest-collarbone approach (GETPCA) compared with open neck surgery for papillary thyroid carcinoma (PTC) .Mthods:Retrospective analysis of PTC patients admitted to the Department of Thyroid and Breast Surgery of the Third Affiliated Hospital of Anhui Medical University from Jan. 2022 to Dec. 2023,and randomly divided into the open group and the lumbo-scopic group according to whether or not they had a requirement for an unmarked neck, in which the open group was n=100,and the lumbo-scopic group was n=67,with 39 male cases and 128 female cases. Clinicopathological characteristics, surgery-related indexes, postoperative complications, postoperative pain scores and postoperative cosmetic satisfaction were compared between the two groups.The t-test,Wilcoxon rank-sum test, χ2 test, consecutively corrected χ2 test, or Fisher’s exact probability method were used to compare the groups. Results:No recurrence was seen during the follow-up period,and none of the cases in the luminal group was open in the middle. The differences in age, body mass index BMI, gender, relative tumor location,preoperative TSH, T stage and N stage between the two groups were not statistically significant ( P>0.05) . The total operation time [ (121.07±39.80) min vs. (93.87±26.97) min]in the luminal group was greater than that in the open group,intraoperative bleeding was less than that in the open group, and the postoperative drainage flow[ (130.69±31.01) mL vs. (105.52±32.71) mL] was greater than that in the open group in the postoperative period of 72 h, and the difference was statistically significant ( P<0.001) .There was no statistical difference between the two groups in terms of 24-h postoperative drainage volume, number of central zone lymph node dissection, number of positive central zone lymph nodes,postoperative hospitalization days or total hospitalization cost ( P>0.05) .The number of cases of neck discomfort (3 cases vs.23 cases, P<0.001) and swallowing dysfunction (2 cases vs.20 cases, P=0.003) in the luminal group was smaller than that in the open group,and the difference was statistically significant.The difference in the incidence of bleeding,incision infection,seroma,temporary recurrent laryngeal nerve injury and temporary parathyroid gland injury between the two groups was also not statistically significant ( P>0.05) .The postoperative NRS on day 1 and postoperative NRS on day 3 of the luminal group were lower than those of the open group,and the difference was statistically significant ( P>0.05) ,while there was no statistically significant difference between the postoperative NRS on day 7,the postoperative NRS on month 1 and the postoperative NRS on month 3 ( P>0.05) .Cosmetic satisfaction at 6 months postoperatively was higher in the luminal group than in the open group,and the difference was statistically significant ( P<0.001) . Conclusion:GETPCA for the treatment of the PTC is safe and feasible,with satisfactory cosmetic results and reduction of neck discomfort and swallowing dysfunction,which is worthy of clinical popularization.

To investigate the mutations of NF1 and clinical phenotypes in patients with sporadic neurofibromatosis type 1 (NF1). This is aimed to evaluate the efficacy of high-throughput sequencing in diagnosing atypical cases, to expand the mutational spectrum of NF1, and to provide early diagnosis of NF1. Clinical data from 11 sporadic NF1 patients without family history treated at the Fifth Affiliated Hospital of Sun Yat-sen University (2019-2023) were collected. The mutations of NF1 gene were detected using whole-exome sequencing or chip-capture high-throughput sequencing, followed by bioinformatics analysis. Novel mutations were screened against normal population databases to exclude benign polymorphisms, and pathogenicity of the mutations was classified according to ACMG guidelines. The results showed that two novel frameshift mutations were identified: c.7904del (p.Asp2635Valfs*9) and c.5122_5123del (p.Phe1708Hisfs*9). The patient carrying c.7904del exhibited an undocumented phenotype of posterior medullary ischemic degeneration. Among the 11 NF1 patients, the types of mutations included frameshift (4/11), nonsense (3/11), intronic (2/11), splicing (1/11), and start codon variants (1/11). Common phenotypes were cafe-au-lait macules (8/11) and neurofibromas (6/11), yet significant phenotypic heterogeneity existed among patients sharing identical mutations. In conclusion, this study discovered two novel NF1 mutations and an unreported phenotype, expanding both the NF1 mutational spectra and highlights the need for attention to cerebrovascular status in patients carrying NF1 mutations. High-throughput sequencing significantly enhances molecular diagnostic efficacy for atypical NF1, providing a critical basis for clinical NF1 diagnosis.

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism. Notably, TH-407b not only effectively inhibited TLR7-mediated pro-inflammatory signaling in a variety of cultured cell lines but also demonstrated potent inflammation suppressing activities in primary peripheral blood mononuclear cells (PBMCs) derived from SLE patients. Furthermore, TH-407b showed prominent efficacy in vivo, improved survival rate and ameliorated symptoms of SLE model mice. To obtain molecular insights into the TH-407b derivatives' inhibition mechanism, we performed the structural analysis of TLR7/TH-407b complex using cryogenic electron microscopy (cryo-EM) method. As an atomistic resolution cryo-EM structure of the TLR family, it not only of value to facilitate structure-based drug design, but also shed light to methodology development of small proteins using EM. Significantly, TH-407b has unveiled an inhibition strategy for TLR7 via stabilizing its resting/inactivated state. Such a resting state could be generally applicable to all TLRs, rendering a useful method for targeting this group of important immunological receptors.

A novel amide alkaloid,bursatamide A(1),featuring an unprecedented propyl-hexahydronaphthalene carbon frame-work,was isolated from the infrequently studied sea hare Bursatella leachi,alongside a new 3-phenoxypropanenitrile alkaloid,bursatellin B(2),and twelve known compounds.The structures of 1 and 2 were elucidated through comprehensive spectroscopic data analyses,while their relative and absolute configurations(ACs)were established through total synthesis and a series of quantum chem-ical calculations,including calculated electronic circular dichroism(ECD)spectra,optical rotatory dispersion(ORD)methods,and DP4+probability analyses.Bursatamide A(1)demonstrated inhibitory effects against the human pathogenic bacteria Listeria monocyt-ogenes and Vibrio cholerae.Erythro-bursatellin B(21),a diastereoisomer of 2,exhibited notable antibacterial activity against the fish pathogenic bacterium Streptococcus parauberis FP KSP28,with an MIC90 value of 0.0472 μg·mL-1.

Aiming at the medical service robot used in the indoor environment, this study proposes a method to test the pose accuracy of its working surface based on the binocular vision system. This method uses a binocular vision coordinate system to measure targets fixed on the working surface of the service robot, aligns the measurement system with the robot base coordinate system through the nonlinear least squares method, and integrates the multi-eye image data to achieve the accuracy test of the working surface. Finally, the vision test program was tested and verified on a mobile service robot model ABIR X8. According to the accuracy index given in GB/T 38124 Service Robot Performance Test Method, the test results of its pose accuracy were obtained.
Optical Devices ; Robotics ; Vision, Binocular

Objective:This study aimed to discover the HIV infection and associated factors among male sex workers (MSW) who provide sexual services for men. Data from this study thus can be used to provide evidence for designing related intervention programs.Methods:In this observational study, MSW were recruited from May to July, 2019 in KTV venues in Wuxi, China. A questionnaire was used to collect information with blood sample collected and tested for HIV and syphilis. EpiData 3.0 and SPSS 17.0 software were used to clean up data and statistical analysis.Results:A number of 500 MSW were involved including 243 (48.6 %) heterosexual and 257 (51.4 %) homosexual MSW. The overall HIV prevalence was 5.4 %(27/500) among all the MSW. there were significant differences between the HIV prevalence rates, the heterosexual MSW (3.3 %, 8/243) and the homosexual MSW (7.4 %, 19/257)( χ2=4.112, P=0.043). In the past 3 months, 28.0 % (72/257) of the homosexual MSW mainly engaged in receptive anal sex which was higher than 11.5 %(28/243) of the heterosexual MSW. Compared to 15.6 % (40/257) of the homosexual MSW who engaged in heterosexual behavior, a higher proportion of 98.4 % (239/243) was noticed among the heterosexual MSW. Higher percentage (44.9 %, 109/243) appeared among the heterosexual MSW who had not been tested for HIV than the homosexual MSW (20.6 %, 53/257). Results from logistic regression multivariate analysis showed that age ≥30 (a OR=7.54, 95 %CI: 2.53-37.11), having unprotected anal sexual practice (a OR=3.76, 95 %CI:1.15-12.23), having anal sex after drinking alcohol (a OR=10.91, 95 %CI: 2.29-51.87) and syphilis tested positive (a OR=8.23, 95 %CI:1.29-52.51) were risk factors associated with HIV infection among the heterosexual MSW. Having unprotected anal sexual behavior (a OR=2.94, 95 %CI: 1.17-7.37), having group anal sex (a OR=4.08, 95 %CI:1.05-15.81), without record on HIV testing (a OR=6.58, 95 %CI: 2.01-18.06) and syphilis tested positive (a OR=4.55, 95 %CI: 1.15-18.06) were risk factors associated with HIV among the homosexual MSW. Conclusions:High HIV prevalence was discovered among both heterosexual and homosexual MSW in Wuxi, China. Differences in sexual behaviors between these two groups should be considered when designing targeted HIV intervention programs for these populations.

OBJECTIVE： To establish a method for simultaneous determination of α-pinene， β-pinene， limonene and α-terpineol in volatile oil of Forsythia suspensa. METHODS： GC method was adopted. The determination was performed on HP-5 capillary column through temperature-programmed route. The inlet temperature was 230 ℃， and detector temperature was 250 ℃； split sampling was applied （split ratio of 8 ∶ 1）； the air flow rate was 300 mL/min， the hydrogen flow rate was 30   mL/min， the tail gas flow rate was 30 mL/min， and the injection volume was 1 μL. Using limonene as internal reference， relative correction factors of α-pinene， β-pinene and α-terpineol were established， and the reproducibility of relative correction factors were investigated by using different chromatographs and columns， and chromatographic peak location of components was measured. The contents of above components were calculated with QAMS， and then compared with the results of external standard method. RESULTS： The linear range of α-pinene， β-pinene， limonene and α-terpineol were 16.5-990.0， 38.1-2 287.5， 8.2-491.2， 2.4-142.5  μg/mL， respectively （r≥0.999 1）. RSDs of precision， reproducibility and stability tests were all lower than 3％ （n＝6）. Average recoveries were 99.7％-105.5％（RSD＜4％，n＝9）. Compared with limonene （1.00），the average relative correction factors of α-pinene， β-pinene and α-terpineol were 0.91，0.86 and 1.11（n＝3）； relative retention time were 0.69-0.74， 0.81-0.86， 1.25-1.35（RSD＜3％，n＝3）. By using different chromatographs and columns， RSDs of relative correction factors were 0.21％-4.65％（n＝6）. Compared with external standard method， determination results of above 4 components were consistent （the absolute value of relative error were all less than 7％）. CONCLUSIONS： QAMS can be used for simultaneous determination of 4 kinds of effective components in volatile oil from F. suspensa.