Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.
Infant, Newborn ; Humans ; Hair Cells, Auditory, Inner/physiology* ; Ear, Inner/physiology* ; Hair Cells, Auditory/physiology* ; Regeneration/genetics* ; Stem Cells

OBJECTIVE To investigate the effect of individualized repositioning maneuver in the treatment of posterior semicircular canal benign paroxysmal positional vertigo(PC-BPPV)with limited neck movement.METHODS There were 163 patients with PC-BPPV admitted to the Department of Otolaryngology of Xiaolan People's Hospital of Zhongshan from January,2019 to July,2022 who were selected and divided into observation group(57 cases)and control group(106 cases)according to whether there was neck movement limitation or not.The control group was divided into control group 1(51 cases)and control group 2(55 cases)based on different reduction methods.The control group 1 were treated with modified Epley maneuver,and the observation group and the control group 2 were treated with individualized Epley maneuver.The cure rate and effective rate were compared among the three groups.The scores of vestibular symptom index(VSI),Berg balance scale(BBS)and the dimension scores of vertigo handicap inventory(DHI)were compared among the three groups before and after treatment.RESULTS There was no significant difference in the cure rate(84.37%vs.81.82%vs.80.70%)and effective rate(11.76%vs.10.91%vs.12.28%)among the three groups(P>0.05).After treatment,the scores of each dimension of VSI and DHI of PC-BPPV patients of the three groups decreased(P<0.01),and the scores of BBS increased(P<0.01),and there was no statistically significant difference in the scores of VSI(23.19±3.88 vs.23.70±4.01 vs.23.46±3.92),BBS(45.56±5.02 vs.45.14±4.98 vs.44.84±5.11)and each dimension of DHI among the three groups(P>0.05),respectively.CONCLUSION The individual Epley maneuver can effectively improve the vertigo status of patients with PC-BPPV with limited neck movement.

Objective:To analyze the differences in paraspinal muscles between patients with degenerative lumbar spinal stenosis (DLSS) with or without spondylolisthesis and to assess the correlation between these differences and lumbar facet joint degeneration.Methods:The data of 68 patients with DLSS who underwent surgical treatment in our hospital from January 2021 to April 2023 was retrospectively analyzed. Of these, 22 were male (32.4%) and 46 were female (67.6%), with an average age of 69.7±5.9 years (range: 56-80 years). The DLSS group included 35 patients without spondylolisthesis [13 males (37.1%) and 22 females (62.9%)], average age 68.5±5.9 years (range: 56-80 years), while the DLSS+degenerative spondylolisthesis (DS) group included 33 patients with spondylolisthesis [9 males (27.3%) and 24 females (72.7%)], average age 70.9±5.7 years (range: 58-80 years). Magnetic resonance imaging (MRI) scans of the L 3-S 1 intervertebral disc levels were collected from all patients. Using ImageJ software, the cross-sectional area (CSA) and percentage of fat infiltration area (FIA%) of the erector spinae and multifidus muscles were measured. Additionally, the facet joint angle (FJA), facet overhang (FO), and facet effusion (FE) were evaluated using Surgimap software, and their correlation with CSA and FIA% of the paraspinal muscles was analyzed. Results:The FJA and FO in the DLSS+DS group (50.16°±11.08° and 7.67±2.25 mm) were significantly larger than those in the DLSS group (43.51°± 7.75° and 3.88±1.98 mm) ( P<0.05). However, differences in FE between the two groups were not statistically significant. The cross-sectional areas of the multifidus muscles at L 3, 4, L 4, 5, and L 5S 1 in the DLSS+DS group (576.66±112.70 mm 2,, 782.72±141.49 mm 2, and 817.88±185.22 mm 2,, respectively) were significantly smaller than those in the DLSS group (647.37±165.44 mm 2,, 881.20±202.10 mm 2,, and 995.06±211.25 mm 2,, respectively) ( P<0.05). The FIA% of the erector spinae at L 3, 4, L 4, 5, and L 5S 1 in the DLSS+DS group (11.47%±5.14%, 14.84%±6.15%, 20.82%±7.41%) were significantly higher than those in the DLSS group (6.27%±2.83%, 10.81%±4.84%, 16.17%±5.88%) ( P<0.05). Similarly, the FIA% of the multifidus muscles at L 3, 4, L 4, 5, and L 5S 1 in the DLSS+DS group (18.04%±5.88%, 19.67%±5.78%, 19.31%±8.61%) were significantly higher than those in the DLSS group (9.85%±4.39%, 12.27%±3.70%, 14.65%±3.82%) ( P<0.05). No statistically significant differences were found in the CSA of the erector spinae at these levels between the two groups. The CSA of the multifidus muscles at L 3, 4, L 4, 5, and L 5S 1 in both groups were negatively correlated with FJA and FO ( r=-0.318, P=0.008; r=-0.381, P=0.001; r=-0.439, P<0.001; r=-0.290, P=0.016; r=-0.315, P=0.009; r=-0.479, P<0.001). The FIA% of the erector spinae at L 3, 4, L 4, 5, and the multifidus muscles at L 4, 5 and L 5S 1 were positively correlated with FJA ( r=0.352, P=0.003; r=0.344, P=0.004; r=0.300, P=0.013; r=0.359, P=0.003). Additionally, the FIA% of the erector spinae at L 3, 4, L 4, 5, and L 5S 1, and the multifidus muscles at L 3, 4 and L 4, 5 were positively correlated with FO ( r=0.409, P=0.001; r=0.248, P=0.042; r=0.277, P=0.022; r=0.500, P<0.001; r=0.447, P<0.001). There was no correlation between FE and CSA or FIA% of the erector spinae and multifidus muscles at L 3, 4, L 4, 5, and L 5S 1 in either group. Furthermore, FJA was positively correlated with FO ( r=0.369, P=0.002), but no correlation was observed between FE and FJA or FO. Conclusion:Compared to patients with lumbar spinal stenosis, those with degenerative lumbar spinal stenosis with spondylolisthesis exhibit more severe paraspinal muscle atrophy, a more sagittal orientation of the facet joints, and a higher degree of facet joint osteoarthritis. Patients with larger FJA and FO show more severe paraspinal muscle atrophy.

Objective:To explore the challenges in the implementation of drug centralized volume-based procurement policies in hospitals and propose corresponding optimization suggestions.Methods:From August to December 2023, a purposive sampling was conducted to select 11 pharmaceutical experts from tertiary hospitals in China for Delphi method. The survey content included " policy recommendations for promoting the acceleration and expansion of national drug centralized procurement and retaining surplus medical insurance funds for centralized procurement" .Results:Survey participants gave feedback on a set of existing problems found in the implementation of drug centralized procurement policies and proposed corresponding optimization methods. Kendall′s W coefficient of the specialist consultation was 0.332( P<0.05), demonstrating good consistency and concentration of the expert opinions. Among the problems, the score of drug supply guarantee was the highest(mean value of importance was 4.45). At the same time, the recommendation of strengthening monitoring and early warning, coordination and dispatch, and effectively ensuring the supply of centralized drug procurement had the highest score and concentration(mean value of importance was 4.91, coefficient of variation was 0.06). Conclusions:Through Delphi method, this study revealed issues and optimization methods in the implementation of drug centralized procurement policies in hospitals. The findings could provide valuable insights for improvements in the pharmaceutical sector and future policy adjustments.

Multiple thrombosis in the coronary arteries need to be characterized by a thorough determination of the source of the thrombus to distinguish them as thrombosis or coronary embolism.This case was a 38-year-old male patient with chest pain and an electrocardiogram showing acute inferior wall and right ventricular myocardial infarction.Emergency coronary angiography showed thrombosis in the proximal middle of the left anterior descending artery,the opening of the first diagonal artery,and the middle of the right coronary artery,but no obvious stenosis was seen.Postoperative electrocardiogram showed acute inferior wall,right ventricular and anterior wall myocardial infarction,and intensive antithrombotic treatment was applied,elective re-examination of coronary angiography and intraluminal imaging showed mixed plaques and suspicious intimal dissection,indicating the possibility of thrombosis secondary to unstable plaque and coronary dissection,and intensive drug treatment was given.After discharge,the patient was stable during the regular follow-up visits.

For patients at nutritional risk who need nutritional treatment, enteral nutrition should be preferred if there is no contraindication. Enteral nutrition is widely used in acute and critical diseases, inflammatory bowel diseases, perioperative management of gastrointestinal surgeries, and non-mild acute pancreatitis. The basic and clinical research on the mechanism of enteral nutrition therapy has become a hot topic in recent years. The majority believe that enteral nutrition therapy works through regulating mucosal immunity and intestinal microecological balance, but the underlying mechanism is still unclear. This review is focused on the mechanism of action of enteral nutrition, in order to inform future application in disease management and the selection of enteral nutrition formulations.

Objective:Rosin alcohol two glycosidase (pinores inoldiglucoside, PDG) effect on the improvement of the osteoporosis in mice and the possible mechanism of action.Methods:A mouse model of osteoporosis was established by removing bilateral ovaries. According to the random number table method, 50 mice were divided into model (MOD) group (equal volume of normal saline), positive control (PC) group (0.2 mg/kg estradiol), PDG-low dose (L) group (5 mg/kg) PDG), PDG-high dose (H) group (10 mg/kg PDG by gavage) and PDG-H+ML385 group (10 mg/kg PDG by gavage after intramuscular injection of 30 mg·kg-1 ML385), 10 mice in each group; Another 10 mice without any ovarian treatment were selected as sham group (intragastric administration of the same amount of normal saline). After 3 weeks of drug intervention, the serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), interleukin-6 (IL-6) and tumor necrosis factor were detected by enzyme-linked immunosorbent assay (ELISA) -α (TNF-α). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by dual energy X-ray. The mRNA and protein expression levels of nuclear factor related factor 2 (Nrf2), oxidase heme oxygenase 1 (HO-1), quinone oxidoreductase 1 (NQO1) were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot, respectively.Results:The serum ALP levels in Sham, MOD, PC, PDG-L, PDG-H and PDG-H + ML385 groups were (25.88±3.42), (47.42±5.32), (36.20±3.37), (38.95±3.24), (29.66±2.64), (39.57±2.06) U/dL, respectively; The serum trap levels were (2.18±0.40), (4.69±0.83), (3.58±0.38), (3.67± 0.48), (2.93±0.26), (3.81±0.49) U/L, respectively; BMD (153.04±12.96), (86.25±6.71), (126.53±8.99), (119.77±8.84), (139.18±15.94), (92.09±4.17) mg/cm 2; The expression levels of Nrf2 mRNA were 1.00±0.00, 0.35±0.04, 0.67±0.05, 0.54±0.03, 0.82±0.08 and 0.48±0.04, respectively; The expression levels of HO-1 mRNA were 1.00±0.00, 0.25±0.03, 0.56±0.03, 0.47± 0.03, 0.71±0.04 and 0.37±0.04, respectively; The expression levels of nqo1mrna were 1.00±0.00, 0.38± 0.02, 0.63±0.03, 0.58±0.04, 0.79±0.05 and 0.44±0.03, respectively; Nrf2 protein expression levels were 0.98±0.08, 0.26±0.04, 0.52 ±0.06, 0.46±0.03, 0.86±0.07, 0.45±0.05. HO-1 protein expression levels were 0.39±0.02, 0.09±0.01, 0.15 ±0.03, 0.17±0.03, 0.26±0.03, 0.12±0.02. NQO1 protein expression levels were 0.53±0.03, 0.21±0.02, 0.38±0.04, 0.29±0.02, 0.55±0.03, 0.24±0.04, respectively; The levels of serum IL-6 were (104.25±11.35), (515.38±74.48), (351.78± 65.12), (364.73±36.64), (246.18±17.52), (408.93±32.56) pg/ml, respectively; The levels of serum TNF-α were (33.79±3.55), (170.11±19.24), (76.09±8.99), (84.95±6.12), (66.98±3.73), (119.04±9.75) pg/mL, respectively; The serum SOD levels were (258.47±19.25), (72.15±8.12), (187.60±14.63), (152.61±12.36), (204.22±19.65), (138.01±13.62) U/mL, respectively; The serum MDA levels were (2.02±0.27), (4.75±0.73), (3.19±0.46), (3.7±0.49), (2.91±0.42), (4.10 ±0.25) μmol/L respectively. There were significant differences between MOD group and Sham group, or PC, PDG-L, PDG-H, PDG-H+ML385 group and MOD group,or PDG-H+ML385 group and PDG-H ( P<0.05) . Conclusion:PDG can reduce bone inflammation and oxidative stress by activating Nrf2 pathway and improve the state of osteoporosis.

Objective:To analyze the clinical phynotypes of fetuses with 22q11.2 microduplications.Method:Eleven fetuses were diagnosed with 22q11.2 microduplications among 2 969 cases who underwent prenatal chromosomal microarray analysis from January 2016 to February 2020. The phenotypes, indications for invasive prenatal diagnosis, genetic results, pregnancy outcomes and postnatal clinical presentation were analyzed.Results:There were 6 cases diagnosed with classic 3.0 Mb microduplication (DiGeorge and velocardiofacial syndromes, DGS/VCFS) in the 22q11.2, 1 case with 1.5 Mb proximal microduplication and 4 cases with distal small segment microduplication (E-H). Out of 11 fetuses with 22q11.2 microduplications,7 cases were inherited, 2 cases was de novo and data were not available for 2 cases. Vicular septal defect and anencephalu were diagnosed by ultrasonography in 2 cases,fetal growth restriction was diagnosed in 2 cases,no any abnormalities were found in remaining 7 cases. Seven cases(3 cases of classic 3.0 Mb microduplication, 1 case of proximal microduplication and 3 cases of distal small segment microduplication) were delivered at full-term;and pregnancy was terminated in 4 cases. Seven infants were followed up after birth, 4 infants were normal, 3 showed abnormal phenotypes.Conclusion:The clinical phenotypes after birth of fetuses with 22q11.2 microduplication are diverse. Prenatal genetic counseling is necessary,so that pregnant women and their families can fully understand the possible clinical phenotypes and make informed choices.

Objective:To investigate the clinical characteristics, gene mutation, treatment and prognosis of familial aggregation myelodysplastic syndromes/acute myeloid leukemia (MDS/AML).Methods:The 3 familial aggregation MDS/AML admitted to Shanghai Yangpu District Hospital from August 2012 to March 2019 were collected. The bone marrow examination, gene mutation detection, therapeutic effect and prognosis of the patients were retrospectively analyzed, and the relevant literature was reviewed.Results:In pedigree 1, the survival time of 2 AML patients was 8 months and 1 month, respectively. In pedigree 2, the transformation time of 2 patients diagnosed MDS to AML/high-risk MDS was 4 and 3 months, the survival time was 5 and 8 months, respectively. TP53 and RUNX1 mutations were detected in the older brother. In pedigree 3, the survival time of the AML patient was 13 months, and the MDS patient was stable.Conclusions:Familial aggregation MDS/AML has rapid progression and short survival time, and its diagnosis needs to be combined with family history, cytogenetics, and molecular biology.

Objective:To investigate the role of LncRNA ZBED3-AS1 in osteoblast proliferation and differentiation in osteoporotic rats through regulating miR-339-5p/Notch 1.Methods:The rat models of sham operation (Sham) group and model (Model) group were established, and the bone mineral density (BMD) of rats was examined. Rat osteoblasts were isolated and the expression of ZBED3-AS1 and miR-339-5p was detected by qRT-PCR. The osteoblasts of rats in Sham group and Model group were divided into different groups and transfected. CCK8, alizarin red (AR-S) staining and alkaline phosphatase (ALP) staining were used to detect the proliferation and differentiation ability of cells in each group. The distribution of ZBED3-AS1 in cells was determined by FISH assay. Double luciferase report confirmed the relationship between ZBED3-AS1 and miR-339-5p as well as miR-339-5p and Notch 1.Western blot was used to detect the expression of Notch pathway related factors.Results:The bone mineral density of femur in Model group was significantly lower than that in Sham group ( P=0.0057) . Compared with Sham group, the expression of ZBED3-AS1 in osteoblasts of Model group was lower, while that of miR-339-5p was higher (all P<0.05) . Overexpression of ZBED3-AS1 could promote the proliferation and differentiation of osteoblasts, while knockdown of ZBED3-AS1 could inhibit the proliferation and differentiation of osteoblasts (all P<0.05) . ZBED3-AS1 could regulate miR-339-5p as ceRNA (all P<0.05) . Overexpression of miR-339-5p can inhibit the proliferation and differentiation of osteoblasts, which can be partially saved by overexpression of ZBED3-AS1. Notch 1 was confirmed as a target of miR-339-5p, at the same time, interfering with the expression of ZBED3-AS1/miR-339-5p can affect the expression of Notch-1 protein, and the regulation of ZBED3-AS1/miR-339-5p on osteoblasts may be realized through Notch pathway. Conclusion:ZBED3-AS1 can be used as ceRNA to regulate miR-339-5p, and then affect the proliferation and differentiation of osteoblasts in osteoporotic rats.