[Early vocabulary development in Mandarin children with cochlear implantation].

Objective: To investigate the development of receptive and expressive vocabulary in Mandarin-speaking children with cochlear implants (CI) during the first year after CI activation. Methods: A total of 827 children (411 boys and 416 girls) who were implanted CI before 2.5 years of age from October 2019 to December 2022 in the Department of Auditory Implantation, Shandong Provincial ENT Hospital were included in this study. The Infant Checklist of the Mandarin Early Vocabulary Inventory (EVI) was used to assess the quantity and content of receptive and expressive vocabulary at the time of CI activation and at the 1st, 3rd, 6th, 9th, 12th months post-activation. SPSS 22.0 was used to describe the receptive and expressive vocabulary of CI children at the first year after activation. Results: During the first year after CI activation, CI children's receptive and expressive vocabulary consistently increased with the CI usage. The average number of receptive vocabulary and expressive vocabulary respectively increased from 0 to 178, and from 0 to 97. At the first year of post-activation, the number of receptive and expressive vocabulary of CI children were superior to that of hearing-age matched typical-hearing children, but fell behind of that of chronological age matched typical-hearing children. In terms of lexical categories, receptive and expressive vocabulary was acquired in the following order: nouns, verbs, adjectives, and pronouns. Among the top 50 words that CI children could express, nouns were the most common, then followed by verbs, adjectives, and pronouns. Father's education level can significantly and positively predictethe receptive vocabulary of CI children at the first year post-activation. At the first year after CI activation, the 10th, 25th, 50th, 75th, and 90th percentiles were 113, 149, 178, 202, 223 for the receptive vocabulary, and 9, 37, 97, 148, 188 for expressive vocabulary. Conclusion: For Mandarin speaking children with CI, the receptive and expression vocabulary continuely increased within the first year after CI activation. The ability to grasp receptive vocabulary precedes the ability to express expressive vocabulary. Compared to hearing-age matched typical-hearing children, CI children showed faster rate of the vocabulary growth, and earlier and more frequently verb expression. However, it still larged behind that of chronological age matched hearing normal children. CI children respectively understood and expressed nouns and verbs the first. In children with CI, the first concepts understood and expressed were nouns and verbs. Among the first 50 words expressed, nouns were the most numerous, and the age at which verbs were acquired was earlier than that for hearing-age matched typical-hearing children.

Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

[Application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection in the sphincter-preserving resection of low rectal cancer].

Objectives: To investigate the application value of laparoscopic double stapler firings and double stapling technique combined with rectal eversion and total extra-abdominal resection (LDER) in the anal preservation treatment of low rectal cancer. Methods: Inclusion criteria: (1) age was 18-70; (2) the distance of the lower tumor edge from the anal verge was 4-5 cm; (3) primary tumor with a diameter ≤3 cm; (4) preoperative staging of T1~2N1~2M0; (5) "difficult pelvis", defined as ischial tuberosity diameter<10 cm or body mass index>25 kg/m2; (6) patients with strong intention for sphincter preservation; (7) no preoperative treatment (e.g., chemotherapy, radiotherapy, molecular targeted therapy, or immunotherapy); (8) no lateral lymph node enlargement; (9) no previous anorectal surgery; (10) patients with good basic condition who could tolerate surgery. Exclusion criteria: (1) previously suffered from malignant tumors of the digestive tract or currently suffering from malignant tumors out of the digestive tract; (2) patients with preoperative anal dysfunction (Wexner score ≥ 10), or fecal incontinence. The specific surgical steps are as follows: the distal end of the rectum was dissected to the level of the interspace between internal and external sphincters of anal canal. Five centimeters proximal to the tumor, the mesorectum was ligated, and a liner stapler was used to transect the rectum. The distal rectum with the tumor were then everted and extracted through the anus. The rectum was transected 0.5-1.0 cm distal to the tumor with a linear stapler. Full thickness suture was used to reinforce the stump of the rectum, which was then brought back into the pelvic cavity. Finally, an end-to-end anastomosis between the colon and the rectum was performed. A retrospective descriptive study was performed of the clinical and pathological data of 12 patients with T1-T2 stage low rectal cancer treated with LDER at Henan Provincial People's Hospital from January 2020 to December 2022. Results: All 12 patients successfully completed LDER with sphincter preservation, without conversion to open surgery or changes in surgical approach. The median surgical time was 272 (155-320) minutes, with a median bleeding volume of 100 (50-200) mL. No protective stoma was performed, and all patients received R0 resection. The average hospital stay was 9 (7-15) days. There were no postoperative anastomotic leakage or perioperative deaths. All 12 patients received postoperative follow-up, with a median follow-up of 12 months (6-36 months) and a Wexner score of 8 (5-14) at 6 months postoperatively. There was no tumor recurrence or metastasis during the follow-up period. Conclusions: LDER is safe and effective for the treatment of low rectal cancer.

[Standardization of next-generation sequencing for detecting mutations associated with targeted therapy and immunotherapy based on dynamic pattern of expandable detection range].

Next-generation sequencing (NGS) has laid the foundation for precision oncology care. NGS technologynot only represents an innovation in the methodology but also brings about a revolution in the concept of detecting gene alterations for targeted therapy and immunotherapy of cancers. As basic biomedical research and drug development progress, the landscape of biomarkers associated with gene alterations continues to evolve. Thus, the standardization of NGS-based gene alterations detection should take into account the characteristics of NGS methods and the gene alteration biomarkers. To be specific, whether employed as in vitro diagnostic products or laboratory-developed tests, the detection range can be expanded in response to changes in the clinical evidence level of biomarkers during the process of assay development and clinical application. Such adjustment needs the analytical validation results for supplemented genes or mutant sites within a predefined detection system, which will maximally fulfill the evolving clinical demands in cancer diagnosis and treatment, simultaneously mitigate potential risks effectively. This article primarily discusses the standardization pathway for NGS testing of gene alterations in cancer by focusing on the characteristics of NGS methods, gene alteration biomarkers, and the current status of the standardization of NGS application.

[Pelvic exenteration for late complications of radiation-induced pelvic injury: a preliminary study].

Objective: To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury. Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded. Results: The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100-6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions: TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.

Decreased serum voriconazole levels caused by hepatic enzyme induction after rifapentine discontinuation: a case report and literature review.

BACKGROUND: Rifapentine is a rifamycin with unique bactericidal activity against Mycobacterium tuberculosis. It is also a potent inducer of CYP3A activity. However, the duration of rifapentine-induced hepatic enzyme activity after withdrawal is unclear. CASE REPORT: We report a case of a patient with Aspergillus meningitis treated with voriconazole after discontinuing rifapentine. Within ten days of rifapentine discontinuation, serum levels of voriconazole failed to reach the effective treatment range. CONCLUSIONS: Rifapentine is a potent inducer of hepatic microsomal enzymes. The induction of hepatic enzymes may exceed ten days after rifapentine discontinuation. Clinicians should be reminded of residual enzyme induction by rifapentine, especially when treating critically ill patients.

[Maintenance of efficacy and its predictors after discontinuation of eltrombopag in adults with primary immune thrombocytopenia].

Objective: To determine the efficacy of eltrombopag for primary immune thrombocytopenia (ITP) in adults and the predictive factors for treatment-free response (TFR) . Methods: Clinical data of adults with ITP who received eltrombopag from June 14, 2013 to May 31, 2021 in the Hematology Department of Ruijin Hospital affiliated with Shanghai Jiao Tong University Medical College were retrospectively analyzed. The initial dose of eltrombopag was 25 mg/d, and the maximum dose was 75 mg/d; the dose was adjusted to maintain the platelet count to within 50-150×10(9)/L. Treatment was discontinued according either to the protocol, on the patient's wishes or doctor's judgment (prescription medication), or based on clinical trials. The efficacy of eltrombopag and factors for TFR among patients who achieved complete response and those who discontinued treatment were analyzed. Results: Overall, 106 patients with ITP (33 men and 73 women) were included in the study. The median age of patients was 50 (18-89) years. There were 2, 10, and 94 cases of newly diagnosed, persistent, and chronic ITP, respectively. The complete response rate was 44.3% (47/106), the response rate was 34.0% (36/106), and the overall response rate was 78.3% (83/106). Meanwhile, 83 patients who responded to treatment discontinued eltrombopag; of these, 81 patients were evaluated. Additionally, 17 patients (21.0%) achieved TFR. The median follow-up duration of patients who achieved TFR was 126 (30-170) weeks. The recurrence rate was 17.6% (3/17), and the relapse-free survival rate was 76.5%. The results of univariate analysis revealed that non-recurrence after discontinuation of other treatments for ITP (P=0.001), and platelet count and eltrombopag dose of ≥100×10(9)/L (P=0.007) and ≤25 mg/d (P=0.031), respectively, upon discontinuation of eltrombopag were predictors of TFR; these effects were attributed to prolonged effective duration of eltrombopag. Multivariate analysis showed that there was a correlation between non-recurrence and prolonged effective duration after discontinuation of other treatments for ITP (P=0.002) . Conclusion: Eltrombopag is effective for patients with ITP as it can result in TFR. Predictors for TFR include non-recurrence after discontinuation of concomitant ITP treatment, and platelet count and eltrombopag dose of ≥100 × 10(9)/L and ≤25 mg/d upon discontinuation of treatment, respectively.

[Establishment of early warning indicators of SARS-CoV-2 Omicron variant in Tianjin].

In this study, Delphi method was used to conduct a questionnaire survey on 12 experts to determine the indicators system and the corresponding weight for early warning features of SARS-CoV-2 Omicron in Tianjin.The positive indexes of experts in three rounds of consultations were both 100%. The experts' authority coefficient was 0.79. The Kendall's W coordination coefficients were 0.375, 0.356 and 0.385 respectively (all P<0.05). The indicators system for early warning features of 2019-nCoV Omicron variant had 5 first-level indicators, 10 second-level indicators and 52 third-level indicators. The weight of each indicator was also determined.

Constraints on Sub-GeV Dark Matter-Electron Scattering from the CDEX-10 Experiment.

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.

Exotic Dark Matter Search with the CDEX-10 Experiment at China's Jinping Underground Laboratory.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

[Discussion on relevant issues of Technical Specifications for Occupational Health Surveillance (GBZ 188-2014)].

Technical Specifications for Occupational Health Surveillance (GBZ 188-2014) is an important basis for judging suspected occupational diseases and occupational contraindications. There are crossing over or overlap between occupational contraindications and diagnostic criteria of poisoning damage. Occupational contraindications have different meanings with the degree and range of common diseases or symptoms and the frequency of physical examination during employment conflicts with the current standard. Based on the practice of occupational health examination in a large population, the present study analyzed relevant articles and put forward some suggestions for revision, in combination with clinical medicine, occupational health standards, and diagnostic standards of occupational diseases. The modification could provide a reference for the revision of Technical Specifications for Occupational Health Surveillance and the practice of occupational health examination.

[Diagnostic efficiency and incremental value of myocardial blood flow quantification by CZT SPECT for patients with coronary artery disease].

Objective: To investigate the diagnostic efficiency and incremental value of quantitative myocardial blood flow measurements by Cadmium-Zine-Telluride (CZT) single photon emission computed tomography (SPECT) dynamic myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD) compared with traditional semi-quantitative measurements by MPI. Methods: This is a retrospective, cross-sectional study. We retrospectively analyzed clinical data of patients with suspected or known CAD, who underwent the dynamic MPI quantitative blood flow measurement of CZT SPECT in TEDA International Cardiovascular Hospital from October 2018 to December 2020. Clinical data, semi-quantitative parameters (stress score (SS), rest score (RS) and different score (DS)) and myocardial quantitative blood flow parameters (rest myocardial blood flow (rMBF), stress myocardial blood flow (sMBF) and myocardial flow reserve (MFR)) were analyzed. According to the results of coronary angiography, patients were divided into the stenosis group and the control group with coronary artery stenosis ≥50% or ≥75% as the diagnosis criteria. The differences of quantitative and semi-quantitative parameters between the two groups were compared, and the diagnostic efficacy was compared by receiver operating characteristic(ROC) curve. Results: A total of 98 patients with a mean age of (62.1±8.7) years were included in the study, including 66 males (67%). At the patient level, with the positive standard of coronary artery stenosis≥50%, the left ventricle (LV) stress MBF (LV-sMBF) ((1.36±0.45) ml·min-1·g-1) and LV-MFR (1.45±0.43) of the stenosis group were lower than the LV-sMBF ((2.09±0.64) ml·min-1·g-1) and LV-MFR (2.17±0.54) of control group; summed SS and summed DS were higher than control group (all P<0.05). With the positive standard of coronary artery stenosis ≥75%, the LV-sMBF ((1.19±0.34) ml·min-1·g-1) and LV-MFR (1.34±0.35) of stenosis group were lower than the LV-sMBF ((1.94±0.63) ml·min-1·g-1) and MFR (2.00±0.58) of control group; all semi-quantitative parameters were higher than control group (all P<0.05). At the vascular level, with coronary artery stenosis ≥50% as the diagnosis criteria, the sMBF ((1.26±0.49) ml·min-1·g-1) and MFR (1.35±0.46) of stenosis group were lower than the sMBF ((1.95±0.70) ml·min-1·g-1) and MFR (2.05±0.65) of control group; SS and DS were higher than control group (all P<0.05). With coronary artery stenosis≥75% as the diagnosis criteria, the sMBF ((1.12±0.41) ml·min-1·g-1) and MFR (1.25±0.38) of stenosis group were lower than the sMBF ((1.84±0.70) ml·min-1·g-1) and MFR (1.93±0.66) of control group; all semi-quantitative parameters were higher than control group (all P<0.05). With coronary artery stenosis≥50% as the diagnosis criteria and CAG as the reference standard, the AUC and 95%CI of myocardial quantitative blood flow parameters indicated by ROC curve for diagnosis of CAD were 0.830 (0.783-0.877). The sensitivity (86.1% vs. 61.5%), specificity (82.6% vs. 73.8%), positive predictive value (77.8% vs. 62.5%), negative predictive value (89.3% vs. 73.0%) and accuracy (84.0% vs. 68.7%) were all higher than the semi-quantitative parameters (all P<0.05). With coronary artery stenosis≥75% as the diagnosis criteria, the AUC and 95%CI of myocardial quantitative blood flow parameters indicated by ROC curve for diagnosis of CAD were 0.832(0.785-0.879). The sensitivity (89.2% vs. 67.6%), negative predictive value (95.5% vs. 86.2%) and accuracy (80.6% vs. 68.0%) were all higher than semi-quantitative parameters (all P<0.05). Conclusion: Compared with traditional SPECT MPI derived semi-quantitative parameters, diagnostic efficacy for CAD is higher using CZT SPECT quantitative myocardial blood flow parameters, this strategy thus has additional diagnostic benefits and incremental value on the diagnosis of CAD.

[Analysis of the methods and quality assurance of metagenomic next-generation sequencing to detect the microbial cfDNA from blood samples in China].

Objective: To investigate the methods and quality assurance of metagenomic next-generation sequencing (mNGS) to detect the microbial cfDNA (mcfDNA) from blood samples in different laboratories across China. Methods: In October 2020, questionnaires about detecting mcfDNA in blood samples with mNGS were distributed to 80 laboratories across the country. The questionnaire included four parts: pre-analysis, during analysis, post-analysis, and carrying out of performance validation for mNGS. (1) Pre-analysis: the requirements for samples quality, such as collection, storage, the transportation conditions of samples; (2) During analysis: the extraction workflows of mcfDNA, the quality requirements of the library, the application of the sequencing platforms and the bioinformatics analysis pipelines; (3) Post-analysis: the standard of interpretation results for mNGS; (4) Carrying out of performance validation: the minimum detection limit for various pathogens. All laboratories are required to fill in the questionnaire according to the actual situation. The feedback data were summarized and analyzed. Results: The 80 laboratories included 20 medical centers and 60 independent medical laboratories. There were 80.0% (64/80) of laboratories indicated that both plasma and serum samples were used to detect mcfDNA in blood, and the rest of the laboratories (16/80, 20.0%) only used plasma samples. The sequencing platforms used by mNGS laboratories involved in the survey included illumina (49), Beijing Genomics Institute (16), Ion Torrent (13) and Nanopore sequencing (2). There were 87.5% (70/80) of laboratories used the integrated analysis tools built by the third-party laboratories, and other laboratories (12.5%, 10/80) independently built the analysis platform by open-source software. The interpretation criteria of mNGS results varied between laboratories, among which the normalized number of pathogen-specific sequences, relative abundance, genome coverage rate, and the detection of the microorganism in the negative control were the main factors considered by laboratories. Most laboratories (76.3%, 61/80) had carried out the performance validation for the mcfDNA mNGS workflows. The limit of detection of the laboratories-developed mNGS workflows for Gram-positive bacteria, Gram-negative bacteria, fungi, parasites, and other pathogens were mainly distributed at 10-100 copies/ml, DNA virus was mainly distributed at 500-1 000 copies/ml. Conclusions: The mNGS workflows of various laboratories are very different. In order to ensure timely and accurate testing results, every laboratory needs to actively optimize the mNGS testing procedures, improve quality assurance measures, and carry out performance validation before mNGS is widely used in clinical settings.

Quasi-isentropic compression of LiH above 400 GPa using magnetocumulative generator.

The knowledge of high-pressure behavior of LiH is significant for the validation of fundamental theoretical models and applications in thermonuclear materials and potential energy supplies. The compressibility of 7LiH under isentropic compression at high pressure was investigated experimentally and theoretically. The experimental technique for quasi-isentropic compression with low-density materials was developed using the magnetocumulative generator CJ-100 and x-ray flash radiography. The x-ray images and extracted interface of the sample target in dynamic flash radiography experiments were obtained. According to each interface size of the target both before and after compression, the compression ratio of 7LiH and reference material aluminum was obtained. The density of the reference and using its known isentropic curve provide the pressure in the reference. The pressure in 7LiH was deduced from the pressure in the reference and using the calculated gradient correction factor. The quasi-isentropic data point at 438 GPa was obtained experimentally. A semiempirical three-term complete equation of state was constructed and validated for 7LiH using the theory of Mie-Grüneisen-Debye with experimental data from the literature. The quasi-isentrope data point is reasonably consistent with the theoretical results. The quasi-isentropic experimental techniques and results broaden the existing research scope and are practical and helpful to further validate theoretical models in the future.

[Problems to be solved in the development from the perspective of future application scenarios of telesurgery].

Telemedicine, which integrates medicine, communication, engineering, information and other disciplines, is a hot emerging cross field in recent years. With the development of telecommunication technology and surgical robot, telesurgery is regarded as the "crown pearl" in telemedicine and has attracted more and more attention. As an extension of traditional surgery, telesurgery greatly extends the connotation and concept of surgery and embodies the great leap forward development of surgical technology. Despite the current limitations such as network delay, transparency of remote robot operation and team construction of surgeons, telesurgery has still formed a variety of innovative application scenarios and achieved rapid development in China in recent years. In view of the uneven distribution of medical resources in China and the epidemic of COVID-19 in the world, this paper puts forward the possible problems and solutions in the development of telesurgery, and looks forward to the feasibility of telesurgery technology in process of shifting the focus of medical and health care down to the community level, channeling resources accordingly.