Objective:The aim of this study was to present an institution's experience with cochlear reimplantation（CRI）, to assess surgical challenges and post-operative outcomes and to increase the success rate of CRI. Methods:We retrospectively evaluated data from 76 reimplantation cases treated in a tertiary center between 2001 and 2022. Clinical features include caused of CRI, type of failure, surgical issues, and auditory speech performance were analyzed. Categorical Auditory Performance （CAP） and Speech Intelligibility Rating （SIR） scores were used to evaluate pre-and post-CRI outcomes. Our center's consecutive cohort of 1 126 patients had seven patients, while 69 patients were from other cochlear implant centers. Device failure was the most common cause of CRI（68/76）, with the remaining cases including flap complications（3/76）, magnet displacement（3/76）, secondary meningitis（1/76）, and foreign bodies around the implant（1/76）. Postoperative auditory and speech outcome improved in 31.6%（24/76） of patients, remained unchanged in 63.2%（48/76）, and decreased in CAP and SIR scores in 5.2%（4/76） of patients. Postoperatively, the seven patients with cochlear ossification and fibrosis scored lower on the overall CAP and SIR scale than non-ossification individuals, which is a significant factor in surgical success rates and auditory-speech outcomes. Conclusion:CRI surgery is a challenging but relatively safe procedure, and most reimplanted patients experience favorable postoperative outcomes. Medical complications and intracochlear damage are the main causes of poor postoperative results. Therefore, minimally invasive CI has a positive significance for reducing the difficulty of CRI surgery and improving the CI performance.
Humans ; Cochlear Implantation/methods* ; Retrospective Studies ; Cochlear Implants ; Male ; Female ; Postoperative Period ; Treatment Outcome ; Adult ; Speech ; Middle Aged ; Postoperative Complications ; Replantation ; Cochlea/surgery*

OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

Five new flavan-4-ol glycosides jixueqiosides A-E (1-5) and two new flavan glycosides jixueqiosides F and G (6 and 7), along with twelve known flavan-4-ol glycosides (8-19), were isolated from the roots of Pronephrium penangianum. Comprehensive spectral analyses, X-ray single-crystal diffraction, and theoretical electronic circular dichroism (ECD) calculations established structures and absolute configurations. A single crystal structure of flavan-4-ol glycoside (14) was reported for the first time, while the characteristic ECD and NMR data for all isolated flavan-4-ol glycosides (1-5 , 8-19) were analyzed, establishing a set of empirical rules. Activity screening of these isolates showed that 8 and 9 could inhibit the proliferation of MDA-MB-231 and MCF-7 cells with IC₅₀ values of 7.93 ? 2.85 ?mol?L^-1 and 5.87 ? 1.58 ?mol?L^-1 (MDA-MB-231), and 2.21 ? 1.38 ?mol?L^-1 and 3.52 ? 1.55 ?mol?L^-1 (MCF-7), respectively. Western blotting and flow cytometry analyses demonstrated that 8 and 9 dose-dependently induced apoptosis in MDA-MB-231 cells by up-regulating BAX, activating caspase-3 and down-regulating BCL-2. Additionally, compound 8 affected autophagy-related proteins, increasing the ratio of LC3-II/LC3-I and Beclin-1 levels to inhibit MDA-MB-231 cell proliferation. Moreover, anti-inflammatory studies indicated that 2, 3, 7, 13, 14, and 18 moderately inhibited tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and nitric oxide (NO) release.
Humans ; Plant Roots/chemistry* ; Glycosides/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Flavonoids/isolation & purification* ; Cell Proliferation/drug effects* ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Molecular Structure ; Apoptosis/drug effects* ; Cell Line, Tumor ; Tumor Necrosis Factor-alpha/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Interleukin-6/immunology* ; Animals ; Mice

With the rapid advancement of synthetic biology, CRISPR-Cas systems have emerged as a powerful tool for gene editing, demonstrating significant potential in various fields, including medicine, agriculture, and industrial biotechnology. This review comprehensively summarizes the significant progress in applying artificial intelligence (AI) technologies to the design, mining, and modification of CRISPR-Cas systems. AI technologies, especially machine learning, have revolutionized sgRNA design by analyzing high-throughput sequencing data, thereby improving the editing efficiency and predicting off-target effects with high accuracy. Furthermore, this paper explores the role of AI in sgRNA design and evaluation, highlighting its contributions to the annotation and mining of CRISPR arrays and Cas proteins, as well as its potential for modifying key proteins involved in gene editing. These advancements have not only improved the efficiency and precision of gene editing but also expanded the horizons of genome engineering, paving the way for intelligent and precise genome editing.
CRISPR-Cas Systems/genetics* ; Artificial Intelligence ; Gene Editing/methods* ; RNA, Guide, CRISPR-Cas Systems/genetics* ; Machine Learning ; Humans ; Genetic Engineering/methods* ; Synthetic Biology

Objective:To explore the perioperative precautions, rehabilitation effect, and affecting factors in cochlear implantation (CI) among patients with hereditary syndromic hearing loss.Methods:This was a retrospective cohort study. 47 patients diagnosed as hereditary syndromic deafness were treated in the Department of Otolaryngology-Head and Neck Surgery of the Chinese PLA General Hospital from 2010 to 2021, including 26 males and 21 females, aged 0.9-25 years. All patients received unilateral or bilateral CI. Clinical manifestation combined with genetic testing was used to diagnose syndromic hearing loss. The risks and precautions of CI in these patients were summarized from preoperative imaging, intraoperative observations, and postoperative complications. Single factor linear regression and multiple linear regression models in SPSS 26.0 software were used to evaluate the effects of various factors on auditory and speech rehabilitation after CI for syndromic hearing loss. The postoperative outcomes were analyzed through aided hearing thresholds, categories of auditory performance (CAP) scale, and speech intelligibility rate (SIR) scale.Results:Thirteen kinds of syndromes, totally 47 cases, including CHARGE (20 cases), Waardenburg (9 cases), Autosomal dominant deafness-onychodystrophy (DDOD, 4 cases), Pendred (3 cases), Noonan Syndrome with Multiple Lentigines (NSML, 2 cases), Branchio-Oto-Renal (BOR, 2 cases), Bart-Pumphery (1 case), Perrault (1 case), Kabuki (1 case), Frontometaphyseal dysplasia type 2 (FMD 2, 1 case), Mandibulofacial dysostosis Guion-Almeida type (MFDGA, 1 case), Coffin-Siris (1 case), and 10q26.12-q26.3 del (1 case), were enrolled. The perioperative special management included the following measures. For patients with cardiac and/or cartilage development issues, preoperative assessments of cardiac function and/or laryngeal cartilage development were performed to minimize anesthetic risks. For patients with mild intellectual disability and/or an auditory neuropathy phenotype, preoperative communication with the patients′ families was conducted to explain the limitations of CI and assist in setting reasonable expectations. For syndromic hearing loss patients who commonly present with inner ear malformations, facial nerve anomalies, and/or intraoperative cerebrospinal fluid leakage, appropriate electrodes were selected prior to surgery, intraoperative facial nerve monitoring and careful cerebrospinal fluid leak repair were conducted, respectively. For patients with NSML accompanied by coagulation issues, the postoperative compression bandaging duration was extended to reduce the risk of hematoma formation. The daily duration of cochlear implant use, the presence of cochlear malformation, and developmental delay were independent factors influencing postoperative CAP scores. The daily duration of cochlear implant use, developmental delay, and unilateral or bilateral CI were independent factors influencing postoperative SIR scores.Conclusions:Hereditary syndrome deafness is a rare disease that affects multiple organs and causes extensive functional impairment. Before CI, a comprehensive evaluation of major affected organ functions is required to assess anesthetic and surgical risks. Genetic diagnosis not only identifies the molecular etiology of patients with syndromic hearing loss and reveals rare phenotypes, but also aids in prognostic evaluation. The main factors affecting CI outcomes in patients with syndromic hearing loss include the presence of cochlear malformations, developmental delays, daily duration of cochlear implant use, and bilateral implantation status.

Objective:To investigate the association between blood pH measured by blood gas analysis during the first postnatal week and mortality in periviable extremely preterm infant (PEPI).Methods:This retrospective study analyzed 48 PEPIs (gestational age<24 weeks) admitted to the neonatal intensive care unit of Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University between January 2021 and December 2023. According to the clinical outcomes during hospitalization, they were divided into two groups: death group ( n=12, including deaths despite active treatment and deaths due to treatment withdrawal) and survival group ( n=36, including cured and improved cases). Blood gas pH and base excess (BE) values during the first week were collected. Mann-Whitney U test and Chi-square test (or Fisher exact test) were used to compare maternal perinatal conditions and neonatal blood pH values between the two groups. The percentiles ( P3 and P90) of blood pH and BE values were described for the survival group by age. Results:(1) Among the 48 PEPIs, four were born at 21 weeks, 11 at 22 weeks, and 33 at 23 weeks of gestation. The clinical outcomes showed a cure rate of 60.4% (29/48), improvement rate of 14.6% (7/48), mortality due to poor prognosis with treatment withdrawal of 8.3% (4/48), and mortality under active treatment of 16.7% (8/48). (2) There was statistically significant difference in the death after treatment withdrawal among the PEPIs born at 21, 22, and 23 weeks of gestation [1/4, 2/11, and 3.0% (1/33); χ2=7.41, P=0.025]. The death group had higher proportions of infants with Apgar score≤3 at 1, 5, or 10 min after birth as compared with the survival group [7/12 vs. 25.0% (9/36), χ 2=4.50; 7/12 vs.16.7% (6/36), χ 2=7.91; 5/12 vs. 5.6% (2/36), χ 2=9.42; all P<0.05]. (3) The median blood pH values in the death group were lower than those in the survival group at 1-4, and 6 d after birth [7.13 (7.06-7.24) vs. 7.25 (7.23-7.31), Z=－3.44; 7.03 (7.00-7.18) vs. 7.21 (7.16-7.24), Z=－3.07; 7.02 (7.02-7.11) vs. 7.18 (7.13-7.21), Z=－3.51; 7.14 (7.13-7.20) vs. 7.18 (7.16-7.21), Z=－2.38; 7.15 (7.13-7.19) vs. 7.19 (7.17-7.22), Z=－2.08; all P<0.05].The pH value of the deceased infants rapidly declined within three days after birth, with the median pH values at two days and three days of age both falling below 7.05. In deceased infants due to poor prognosis, the median pH value at 4-7 days of age remained consistently at or below 7.15. In the survivors, the blood pH and BE values decreased after birth and hit the bottom at 3 and 5 days of age, respectively ( P3: pH=7.10, BE=－16.10 mmol/L) before gradual recovery. Conclusions:PEPI tend to present with low blood pH during the first postnatal week. However, excessively low blood pH warrants vigilance against adverse outcomes.

Objective:To explore the perioperative precautions, rehabilitation effect, and affecting factors in cochlear implantation (CI) among patients with hereditary syndromic hearing loss.Methods:This was a retrospective cohort study. 47 patients diagnosed as hereditary syndromic deafness were treated in the Department of Otolaryngology-Head and Neck Surgery of the Chinese PLA General Hospital from 2010 to 2021, including 26 males and 21 females, aged 0.9-25 years. All patients received unilateral or bilateral CI. Clinical manifestation combined with genetic testing was used to diagnose syndromic hearing loss. The risks and precautions of CI in these patients were summarized from preoperative imaging, intraoperative observations, and postoperative complications. Single factor linear regression and multiple linear regression models in SPSS 26.0 software were used to evaluate the effects of various factors on auditory and speech rehabilitation after CI for syndromic hearing loss. The postoperative outcomes were analyzed through aided hearing thresholds, categories of auditory performance (CAP) scale, and speech intelligibility rate (SIR) scale.Results:Thirteen kinds of syndromes, totally 47 cases, including CHARGE (20 cases), Waardenburg (9 cases), Autosomal dominant deafness-onychodystrophy (DDOD, 4 cases), Pendred (3 cases), Noonan Syndrome with Multiple Lentigines (NSML, 2 cases), Branchio-Oto-Renal (BOR, 2 cases), Bart-Pumphery (1 case), Perrault (1 case), Kabuki (1 case), Frontometaphyseal dysplasia type 2 (FMD 2, 1 case), Mandibulofacial dysostosis Guion-Almeida type (MFDGA, 1 case), Coffin-Siris (1 case), and 10q26.12-q26.3 del (1 case), were enrolled. The perioperative special management included the following measures. For patients with cardiac and/or cartilage development issues, preoperative assessments of cardiac function and/or laryngeal cartilage development were performed to minimize anesthetic risks. For patients with mild intellectual disability and/or an auditory neuropathy phenotype, preoperative communication with the patients′ families was conducted to explain the limitations of CI and assist in setting reasonable expectations. For syndromic hearing loss patients who commonly present with inner ear malformations, facial nerve anomalies, and/or intraoperative cerebrospinal fluid leakage, appropriate electrodes were selected prior to surgery, intraoperative facial nerve monitoring and careful cerebrospinal fluid leak repair were conducted, respectively. For patients with NSML accompanied by coagulation issues, the postoperative compression bandaging duration was extended to reduce the risk of hematoma formation. The daily duration of cochlear implant use, the presence of cochlear malformation, and developmental delay were independent factors influencing postoperative CAP scores. The daily duration of cochlear implant use, developmental delay, and unilateral or bilateral CI were independent factors influencing postoperative SIR scores.Conclusions:Hereditary syndrome deafness is a rare disease that affects multiple organs and causes extensive functional impairment. Before CI, a comprehensive evaluation of major affected organ functions is required to assess anesthetic and surgical risks. Genetic diagnosis not only identifies the molecular etiology of patients with syndromic hearing loss and reveals rare phenotypes, but also aids in prognostic evaluation. The main factors affecting CI outcomes in patients with syndromic hearing loss include the presence of cochlear malformations, developmental delays, daily duration of cochlear implant use, and bilateral implantation status.

Objective:To investigate the association between blood pH measured by blood gas analysis during the first postnatal week and mortality in periviable extremely preterm infant (PEPI).Methods:This retrospective study analyzed 48 PEPIs (gestational age<24 weeks) admitted to the neonatal intensive care unit of Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University between January 2021 and December 2023. According to the clinical outcomes during hospitalization, they were divided into two groups: death group ( n=12, including deaths despite active treatment and deaths due to treatment withdrawal) and survival group ( n=36, including cured and improved cases). Blood gas pH and base excess (BE) values during the first week were collected. Mann-Whitney U test and Chi-square test (or Fisher exact test) were used to compare maternal perinatal conditions and neonatal blood pH values between the two groups. The percentiles ( P3 and P90) of blood pH and BE values were described for the survival group by age. Results:(1) Among the 48 PEPIs, four were born at 21 weeks, 11 at 22 weeks, and 33 at 23 weeks of gestation. The clinical outcomes showed a cure rate of 60.4% (29/48), improvement rate of 14.6% (7/48), mortality due to poor prognosis with treatment withdrawal of 8.3% (4/48), and mortality under active treatment of 16.7% (8/48). (2) There was statistically significant difference in the death after treatment withdrawal among the PEPIs born at 21, 22, and 23 weeks of gestation [1/4, 2/11, and 3.0% (1/33); χ2=7.41, P=0.025]. The death group had higher proportions of infants with Apgar score≤3 at 1, 5, or 10 min after birth as compared with the survival group [7/12 vs. 25.0% (9/36), χ 2=4.50; 7/12 vs.16.7% (6/36), χ 2=7.91; 5/12 vs. 5.6% (2/36), χ 2=9.42; all P<0.05]. (3) The median blood pH values in the death group were lower than those in the survival group at 1-4, and 6 d after birth [7.13 (7.06-7.24) vs. 7.25 (7.23-7.31), Z=－3.44; 7.03 (7.00-7.18) vs. 7.21 (7.16-7.24), Z=－3.07; 7.02 (7.02-7.11) vs. 7.18 (7.13-7.21), Z=－3.51; 7.14 (7.13-7.20) vs. 7.18 (7.16-7.21), Z=－2.38; 7.15 (7.13-7.19) vs. 7.19 (7.17-7.22), Z=－2.08; all P<0.05].The pH value of the deceased infants rapidly declined within three days after birth, with the median pH values at two days and three days of age both falling below 7.05. In deceased infants due to poor prognosis, the median pH value at 4-7 days of age remained consistently at or below 7.15. In the survivors, the blood pH and BE values decreased after birth and hit the bottom at 3 and 5 days of age, respectively ( P3: pH=7.10, BE=－16.10 mmol/L) before gradual recovery. Conclusions:PEPI tend to present with low blood pH during the first postnatal week. However, excessively low blood pH warrants vigilance against adverse outcomes.

Purpose To explore the ability of proton density fat fraction(PDFF)and decay constant T2* values in MRI to reflect skeletal muscle aging.Materials and Methods 3T MRI data of skeletal muscle in the middle thigh of 211 healthy adults from the Third Affiliated Hospital of Southern Medical University from August to December 2023 were prospectively collected.Gender,age,height,weight and body mass index(BMI)were recorded.PDFF value and T2* value of thigh skeletal muscle were measured at post-processing workstation,and statistical differences among different age,gender and BMI groups were analyzed.The correlation between PDFF value and T2* value of thigh skeletal muscle and age and BMI was analyzed.Results There were statistically significant differences in PDFF values of thigh skeletal muscle among different age groups(H=18.476-85.619,all P<0.01).There were significantly differences in T2*values of the left and right quadriceps muscles,hamstrings and adductors among different age groups(H=13.342-47.566,all P<0.05).There were statistically significant differences in the PDFF values of right quadriceps,left and right hamstring,adductor and sartor muscles between male and female groups(Z=-4.929--1.626,all P<0.05),while there were statistically significant differences in T2* values of left sartor muscle(Z=-2.971,P=0.003).There was no statistical significance in PDFF value of skeletal muscle of thigh in different BMI groups(P>0.05),but there were statistically significant differences in T2* value of left and right quadriceps muscle,hamstring muscle and adductor muscle(H=9.542-24.495,all P<0.05).There was a moderate positive correlation between age and PDFF value of thigh skeletal muscle(r=0.635,P<0.01),but a slight negative correlation with T2* value of left and right quadriceps,hamstring and sarcoleus(r=-0.451--0.189,all P<0.01).There was a slight positive correlation between BMI and T2* values of thigh skeletal muscle(r=0.317,P<0.01).There was a moderate negative correlation between the PDFF value and T2* value of all thigh skeletal muscles(r=-0.749--0.624,P<0.01).The PDFF and T2* values of the front and back thigh muscles(quadriceps,hamstring)were most significantly correlated with age and BMI.Conclusion PDFF based on MRI can reflect the age-related changes in the microenvironment of thigh skeletal muscle,and is a potential imaging biological marker for accurate and non-invasive quantitative evaluation of thigh skeletal muscle aging.

Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines.In this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients.We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla.Through conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were validated.By integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm.The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant difference.Finally,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and vanylglycol.Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.