Objectives: . This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice. Methods: . CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays. Results: . Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage. Conclusion . Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.

Objective To explore the regulatory effect and mechanism of disidin domain receptor 1(DDR1)on the proliferation and apoptosis of glioma cells.Methods The expression levels of DDR1 in human glioma cells and normal glial cells were detected by qRT-PCR and Western blot.Glioma cells U251 with stable overexpression and knockdown of DDR1 were constructed by lentivirus infection,the proliferation ability of the stable cell line was detected by CCK-8 assay,and the apoptosis ability was detected by flow cytometry.Western blot was used to detect the activation of related pathways in stable cell lines and explore the regulatory mechanism of DDR1.Results The results of qRT-PCR and Western blot showed that the expression level of DDR1 in human glioma cell U251 was higher than those in human glioma cell U87 and normal glial cell HEB.Therefore,the U251 cell line was selected for subsequent experiments.CCK-8 assay showed that overexpression of DDR1 promote the proliferation of glioma cells,while knockdown of DDR1 inhibit the proliferation of glioma cells.The results of flow cytometry showed that overexpression of DDR1 inhibit the apoptosis of glioma cells,while knockdown of DDR1 induce the apoptosis of glioma cells.Western blot results showed that overexpression of DDR1 activate the PI3K/AKT pathway,while knockdown of DDR1 inhibit the activation of the PI3K/AKT pathway.Conclusion DDR1 can enhance the proliferation ability of glioma cells and inhibit their apoptosis by activating the PI3K/AKT pathway,promoting the development of glioma cells.Therefore,DDR1 may become a potential target for the treatment of glioma.

Objective:To evaluate the efficacy and safety of anlotinib neoadjuvant therapy for newly diagnosed locally advanced thyroid cancer (LATC).Methods:Twenty-four newly diagnosed LATC patients (10 males and 14 females, age (47.1±3.3) years) admitted to Affiliated Hospital of Integrated Traditional Chinese and Western Medicine of Nanjing University of Chinese Medicine were prospectively included from January 2023 to April 2024. Patients were given anlotinib neoadjuvant therapy (12mg/d, 2 weeks of medication, 1 week of discontinuation), and the efficacy of the treatment was evaluated by CT and multi-disciplinary treatment at the end of each treatment cycle. Patients assessed as suitable for surgery would be scheduled for surgery, while those who were not suitable for surgery would continue to receive neoadjuvant therapy and periodic evaluations. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the R0/1 resection rate and adverse events (AE) after neoadjuvant therapy were observed. Paired- t test was used to analyze the differences between groups, and the Clopper-Person accurate method was used to calculate the bilateral 95% CI of ORR and other indicators. Results:Twenty-four patients received 2(2, 3) cycles of neoadjuvant therapy with anlotinib, of which 23 underwent surgery after anlotinib therapy. After neoadjuvant therapy, the mean maximum diameter of target lesions decreased by 23.5%(95% CI: 2.8%-44.3%) compared with baseline ( t=9.22, P<0.001). The ORR and DCR were 37.5%(95% CI: 18.8%-59.4%) and 100%(95% CI: 85.8%-100%), respectively. About 91.7%(95% CI: 73.0%-99.0%) of patients eventually underwent R0/1 resection. Hand and foot skin reactions, hypertension, oral mucositis, and leukopenia were common AE; grade 4 and 5 AE were not observed. Conclusion:Anlotinib can be safely used as neoadjuvant therapy for newly diagnosed LATC patients with good antitumor effects, providing better surgical opportunities for R0/1 resection.

Aim To study the effects of whole herb of Prunella and its active components on the malignant progression of breast cancer and its mechanism.Meth-ods Breast cancer transplantation tumor model was constructed and randomly divided into the model group,low,medium and high dose group of whole herb of Prunella(0.1,0.2,0.4 g·mL-1 by gavage)and paclitaxel(10 mg·kg-1 by intraperitoneal injection),which was administered by gavage every day,and the tumor tissues were collected after 28 days of interven-tion.The weight,tumor volume and mass of nude mice in each group were detected,HE staining was used to observe the morphology of breast cancer tumor tissues,and immunohistochemical staining was used to observe the proliferation of cell-cycle regulatory protein-67(Ki-67)and cytokeratin 17(CK17)in breast cancer tumor tissues.The cellular experiments were performed by u-sing different concentrations of the ethyl acetate extract of the whole herb of Prunella in breast cancer MDA-MB-231 cells for 24 h.The proliferation of MDA-MB-231 cells and the effects on the cell cycle and apoptosis of MDA-MB-231 cells were detected by using the CCK-8 assay,the cell cycle flow and the apoptotic cell flow.Western blot was used to detect the effect of ethyl ace-tate extract of whole herb of Prunella on the expression of apoptosis-related proteins in breast cancer MDA-MB-231 cells.UPLCQ-TOF MS/MS was used to detect the chemical compositions of the ethyl acetate extract of Prunella whole herb.Results The whole herb of Pru-nella had no significant effect on the growth of nude mice(P＞0.05);it could significantly inhibit the growth of transplanted tumors in nude mice with human breast cancer(P＜0.05);the results of HE staining showed that the cells in the tissues appeared to be rela-tively sparse with the increase of the dose of Prunella and had different degrees of nuclear consolidation and deep staining of nuclei and the apoptosis of the tumor cells increased;the metastasis of tumor cells to the liv-er and lungs was inhibited,when compared with that in the model group.Compared with the model group,the low,medium and high groups of Prunella had no signif-icant effect on the liver index,while the spleen index was significantly reduced(P＜0.05);the expression of Ki-67 and CK17 was reduced.The ethyl acetate ex-tract of the whole herb of Prunella could inhibit the proliferation of MDA-MB-231 cells in breast cancer(P＜0.01);the results of flow cytometry showed that,with the increase of the concentration of the ethyl ace-tate extract of the whole herb of Prunella,the proportion of S-phase cells in the MDA-MB-231 cells significantly increased,and the proportion of G0/G1-phase cells sig-nificantly decreased,while the proportion of G2-phase cells did not change significantly(P＜0.01);Western blotting was not affected in the low,medium and high groups,and the spleen index significantly decreased(P＜0.05);the expression of Ki-67 and CK17 was re-duced;the results of Western blot showed that the eth-yl acetate extract of the whole herb of Prunella promo-ted the expression of Bax,cleaved caspase-3,cleaved caspase-9 proteins,and inhibited the expression of Bcl-2,caspase-3,caspase-9,cyclinA2,and CDK2 proteins(P＜0.05,P＜0.01).The acetic acid of the whole herb of Prunella ethyl ester extract identified a total of 51 compounds.Conclusions The whole herb of Pru-nella can inhibit the growth of breast cancer in nude mice transplanted with tumors,promote the apoptosis of tumor cells,inhibit the proliferation of breast cancer MDA-MB-231 cells,inhibit the metastasis of tumor cells to the liver and lungs,protect the liver and spleen,and reduce the expression of the value-added markers Ki-67 and CK17 in tumor tissues,and the ef-fective ingredient of the whole herb,the ethyl acetate extract,can induce apoptosis.The mechanism may be related to the down-regulation of cyclinsA2,CDK2,Bcl-2,caspase-3,caspase-9 and up-regulation of Bax,cleaved caspase-3,cleaved caspase-9 protein expres-sion.

OBJECTIVE: To explore early curative effect of upper joint capsule reconstruction combined with biceps tendon transposition in treating irreparable rotator cuff tears. METHODS: From October 2019 to March 2021, 16 patients with irreparable rotator cuff tear were underwent arthroscopic autogenous semitendinosus tendon transplantation for upper articular capsule reconstruction combined with biceps tendon transposition, included 12 males and 4 females, aged from 53 to 72 years old with an average of (62.13±5.35) years old; 3 patients on the left side and 13 patients on the right side. All patients had preoperatively limited joint mobility, resting pain, and mobility pain, and had a history of failure to respond to conservative treatment for more than 8 months. The duration of preoperative symptoms ranged from 45 to 144 months with an average of (85.25±32.08) months. Visual analogue scale (VAS) of shoulder pain, University of California Los Angeles (UCLA) score, Constant-Murley score, active and passive motion of shoulder joint were compared before operation and 2 years after operation, complications were recorded. RESULTS: All 16 patients were followed up for 21 to 32 months with an average of (24.25±3.57) months. There were no complications such as incision infection, vascular and nerve injury, retear occurred. VAS, UCLA and Constant-Murley scores were improved from (5.75±1.18), (11.88±3.38) and (33.38±9.34) before operation to (1.13±0.89), (32.56±2.71), (89.06±6.25) at 2 years after operation (P<0.05). Anterior flexion, abduction, lateral external rotation and lateral internal rotation of shoulder joint were improved from (79.75±21.36) °, (62.06±10.49) °, (19.19±5.41) °, (3.04±0.21) °, respectively to (156.94±13.18) °, (116.19±12.59) °, (42.63±6.07) °, (8.16±0.64) ° at 2 years after operation. Anterior flexion, abduction, lateral lateral rotation and lateral internal rotation of shoulder joint were improved from (116.28±21.47) °, (107.12±9.67) °, (27.62±4.70) °, (4.21±0.41) °, respectively to (165.28±7.15) °, (153.34±4.69) °, (52.46±4.46) °, (9.68±0.68) ° at 2 years after operation, and the difference was statistically significant (P<0.05). CONCLUSION Arthroscopic autograft of semitendinosus tendon combined with transposition of biceps tendon could achieve satisfactory early clinical results in treating patients with irreparable rotator cuff tear, which is a reliable and effective surgical method.
Humans ; Male ; Female ; Middle Aged ; Aged ; Arthroscopy/methods* ; Rotator Cuff Injuries/physiopathology* ; Plastic Surgery Procedures/methods* ; Range of Motion, Articular ; Shoulder Joint/surgery* ; Tendon Transfer

OBJECTIVE: To explore clinical effect of autologous osteochondral transplantation (AOT) in the treatment of recurrent anterior dislocation of the shoulder joint with glenoid cartilage defect in rabbits by establishing a model of recurrent anterior dislocation of the shoulder joint with < 20% glenoid cartilage defect in rabbits. METHODS: Twenty-four male New Zealand white rabbits, aged 6-month-old, weighed (2.69±0.17) kg were selected. The labrum of shoulder joint of rabbits was artificially destroyed to establish a model of recurrent anterior dislocation of shoulder joint with cartilage defect. They were divided into AOT surgery group and simple suture group, with 12 rabbits in each group. AOT group were underwent AOT surgery, while simple suture group was treated with simple Bankart suture for recurrent shoulder joint dislocation. At 6 and 12 weeks after operation, 6 rabbits between two groups were sacrificed for sampling. The dietary conditions, activity conditions, mental states of rabbits and healing conditions of grafts in the specimens were observed and compared between two groups. HE staining was used to observe cell creep, cell morphology, inflammatory cell infiltration, fibrochondrocytes and their arrangement. Masson staining was used to observe the formation and arrangement of collagen fibers; Safrane-green staining was used to observe the regeneration of articular cartilage, subchondral bone and bone tissue. Bone mineral density (BMD), bone volume (BV) and trabecular thickness (Tb.Th) between two groups were measured by Micro-CT to evaluate the remodeling of shoulder glenoid bone defects by autologous osteochondral cartilage. RESULTS: After different surgical interventions were carried out in both groups of rabbits, at 6 weeks after the operation, the abduction, extension, internal rotation and external rotation of the shoulder joint on the operated side showed limited range of motion compared with the contralateral side, while adduction and forward flexion showed no obvious abnormalities compared with the contralateral side. At 12 weeks after operation, the range motion of tshoulder joints in both groups of rabbits had returned to the state before modeling. The effects of HE staining, Masson staining and safrane-green staining at 12 weeks after operation in both groups were stronger than the staining results at 6 weeks after operation. Moreover, the results of HE staining, Masson staining and safranin fixation green staining in AOT group at 6 and 12 weeks after operation were all higher than those in simple suture group. Micro-CT scan results at 6 and 12 weeks after operation showed that BMD (0.427±0.014), (0.466±0.032) g·cm-3, BV(116.171±3.527), (159.327±3.500) mm3, and Tb.Th (0.230±0.006), (0.285±0.009) mm in AOT group, which were higher than those of simple suture group in BMD(0.358±0.011), (0.384±0.096) g·cm-3, BV(72.657±3.903), (118.713±3.860) mm3, and Tb.Th(0.204±0.009), (0.243±0.007) mm;and the differences were statistically significant (P<0.05). CONCLUSION AOT procedure could effectively promote osteogenesis and fibrocartilage regeneration in the cartilage defect area of the shoulder glenoid <20%, which is conducive to reshaping the structure of the shoulder glenoid.
Animals ; Rabbits ; Male ; Transplantation, Autologous ; Cartilage, Articular/injuries* ; Shoulder Dislocation/physiopathology* ; Bone Transplantation ; Shoulder Joint/surgery*

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

A method for determination and targeted screening of diflorasone components in health products using ultra performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF/MS)was established.Four representative diflorasone and esters(diflorasone,diflorasone diacetate,diflorasone-17-propionate,and diflorasone-21-propionate)were selected to optimize the pretreatment conditions,and 10 mL of extraction solvent dosage,15 min of extraction time and 5 g of salting-out agent as the optimal conditions were selected by response surface methodology.The results showed that the four analytes exhibited good linearity within the concentration range of 2.0?100 μg/L with the chromatographic peak area,and the correlation coefficients(R2)were all greater than 0.9990,while the results of recovery and relative standard deviation could satisfy the requirements of determination.The common characteristic ions of diflorasone and esters werem/z121 andm/z335,and their specific structures were obtained by analyzing the cleavage pathway based on the optimized determination conditions.A targeted screening method for other esters of diflorasone based on characteristic ions guidance strategy was established.This method had many advantages such as high efficiency,high sensitivity and good reproducibility,and could be used for targeted screening of diflorasone and esters in health products.The developed characteristic ion guided strategy could be employed to construct mass spectral databases for various glucocorticoids,enabling comprehensive targeted screening across a broad range of compounds.