ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

OBJECTIVE: To compare the efficacy of percutaneous pedicle screw combined with unilateral nail placement combined with bone cement strengthening and bilateral nail placement in the treatment of osteoporotic thoracic and lumbar fractures. METHODS: A retrospective case-control study was used to analyze the clinical data of 78 patients with osteoporotic thoracic and lumbar fractures admitted from October 2017 to May 2019. According to the surgical method, it was divided into percutaneous pedicle screw combined with unilateral nail placement combined with unilateral bone cement strengthening group(bone cement group) and percutaneous pedicle screw combined with bilateral nail placement(screw group). In the bone cement group, 40 patients included 16 males and 24 females, with a mean age of (62.1±8.1) years old. In the screw group, 38 patients included 18 males and 20 females with a mean age of (65.1±9.3) years old. The operation time, intraoperative blood loss, length of hospital stay and postoperative complications were compared between two groups. The kyphosis Cobb angle, anterior edge height ratio, central height ratio and pain visual analogue score(VAS) were compared. RESULTS: All patients were followed up for 25 to 36 months. The operation time (70.1±17.3) min of the cement group was shorter than that of the screw group (78.6±18.2) min(P<0.05). There were no significant differences in intraoperative blood loss and length of hospital stay(P>0.05). The VAS in the cement group 1 year 1.5±0.5 and the latest follow-up 0.5±0.3 after operation were lower than 1 year 1.8±0.3 and the latest follow-up 0.8±0.4 in the screw group(P<0.05). The kyphosis Cobb angle, anterior edge height ratio, central height ratio in bone cement group, 1 year (6.2±1.2)°, (86.6±3.5)%, (91.1±2.5)%, the last follow-up (6.4±0.7)°, (85.5±3.3)%, (90.5±6.3)% were better than that of the screw group 1 year (6.8±1.4)°, (83.1±2.4)%, (89.9±3.4)% and the latest follow-up (7.1±1.1)°, (82.6±4.1)%, (87.6±5.9)%(P<0.05). There were 3 cases of bone cement leakage in the cement group, all of which had no clinical symptoms;and 2 cases of pedicle screws were extracted in the screw group, and the screws were removed at the last follow-up. CONCLUSION Percutaneous pedicle screw combined with unilateral nail placement combined with bone cement strengthening and bilateral nail placement in the treatment of osteoporotic thoracic and lumbar compression fractures in the elderly can achieve satisfactory efficacy and effectively relieve the pain of patients, but the former internal fixation system is more stable, and the long-term follow-up can effectively maintain the height of the anterior middle column and the correction of kyphosis deformity, and the incidence of chronic low back pain is lower.
Humans ; Male ; Female ; Aged ; Bone Cements ; Middle Aged ; Thoracic Vertebrae/surgery* ; Lumbar Vertebrae/surgery* ; Retrospective Studies ; Spinal Fractures/surgery* ; Osteoporotic Fractures/surgery* ; Case-Control Studies ; Bone Nails ; Pedicle Screws

OBJECTIVE: To explore the efficacy and safety of human epidermal growth factor gel in the treatment of pin tract infections after surgery in patients with severe spinal deformity. METHODS: A retrospective case-control study was conducted to analyze the clinical data of 26 patients with pin tract infections after skull-pelvic ring traction for severe spinal deformity admitted from February 2019 to May 2022. Among them, 11 were male and 15 were female;the age ranged from 18 to 31 years, with an average of (24.1±4.3) years;the Cobb angle ranged 80.3° to 120.7°, with an average of (88.6±10.2)°;there were 52 iliac traction pins, 104 pin tract openings, and 38 pin tract infections. According to the Checketts-Otterbum classification, there were 11 infections of gradeⅠ, 13 infections of gradeⅡ, 10 infections of grade Ⅲ, and 4 infections of grade Ⅳ. The patients were divided into the conventional dressing change group (13 cases) and the growth factor group (13 cases) by coin flipping. Clinical efficacy was evaluated by recording the visual analogue scale(VAS) score during dressing change, duration of dressing change, cost of dressing change, positive rate of bacterial culture, wound improvement rate, and wound improvement time. RESULTS: There were no statistically significant differences in VAS or duration of dressing change between the two groups (P>0.05). The cost of dressing change was (800.0±59.5) yuan in the conventional dressing change group and (1 179.5±80.9) yuan in the growth factor group, with a statistically significant difference (P<0.05). There was no statistically significant difference in the positive rate of bacterial culture between the two groups (P>0.05). In the conventional dressing change group, within 20 pin tract infections, 2 infections achieved wound healing, 7 infections showed improvement, and 11 infections were ineffective;in the growth factor group, within 18 pin tract infections 5 infections achieved wound healing, 8 infections showed improvement, and 5 infections were ineffective, with a statistically significant difference between the two groups (P<0.05). The wound healing time was (22.8±4.9) days in the conventional dressing change group and (14.2±2.5) days in the growth factor group, with a statistically significant difference (P<0.05). No complications occurred in either group. CONCLUSION The application of human epidermal growth factor gel in the treatment of pin tract infections after skull-pelvic ring surgery in patients with severe spinal deformity is easy to operate, does not increase patient pain, and has significant efficacy. It shortens wound healing time, effectively promotes wound healing, and has good safety and high cost-effectiveness.
Humans ; Male ; Female ; Adult ; Adolescent ; Retrospective Studies ; Case-Control Studies ; Young Adult ; Epidermal Growth Factor/therapeutic use* ; Traction/adverse effects* ; Gels ; Bone Nails/adverse effects* ; Surgical Wound Infection/drug therapy*

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer.Methods:A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate.Results:Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side ( P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion:For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

Objective To explore the clinical value of anti-Müllerian hormone(AMH)to optimize endocrine therapy for peri-menopausal early breast cancer.Methods Two hundred and four patients of pre-menopausal breast cancer aged 45-55 years old between 2020 and 2023 were enrolled,and AMH≤0.1 ng/mL was considered as cut-off value for menopause.Switching from selective estrogen receptor modulator(SERM)to aromatase inhibitor aromatase inhibitor(AI)and initial endocrine therapy regimens were based on AMH,follicle-stimulating hormone(FSH)and estradiol(E2).Results Pre-chemotherapy AMH level was significantly negatively correlated with FSH level(P<0.001).Among 100 cases who were amenorrhea for one year during SERM treatment,42 cases did not have AMH testing.Fourteen out of the 42 cases switched to AI within one year,and ovarian function recovery(OFR)occurred in 2 cases after AI switching.Fifteen cases with AMH>0.1 ng/mL did not switch to AI within one year.Forty among 43 cases with AMH≤0.1 ng/mL switched to AI,after a significantly shorter median SERM treatment duration(3.15 months vs.8.14 months,P<0.001)and a significantly lower OFR rate(0 vs.12.5%,P=0.023)compared with those who did not test AMH but switched to AI.AMH≤0.1 ng/mL was an independent risk factor of transition to menopause shortly in peri-menopausal patients(OR=35.857,P<0.001).Among 104 cases with AMH tested before adjuvant chemotherapy,69 cases had AMH>0.1 ng/mL.Thirty-one out of the 69 cases were treated with ovarian function suppression(OFS)initially and 38 with SERM initially.Thirty-five cases with AMH≤0.1 ng/mL were all treated with SERM initially,with a higher rate of switching to AI(71.4%vs.23.7%,P<0.001)and a shorter SERM treatment duration(6.52 months vs.13.56 months,P=0.016)compared with the 38 cases(AMH>0.1 ng/mL)treated initially with SERM.After a median 30-month follow-up,no recurrence was observed in these thirty-five cases treated with SERM initially and AMH≤0.1 ng/mL,just like in OFS group.And they had a tendency of improved survival outcome compared with those treated with SERM initially and AMH>0.1 ng/mL(Log Rank P=0.076).Conclusion AMH could evaluate and predict menopause accurately,resulting in optimizing endocrine therapy for peri-menopausal patients effectively and safely.

Hereditary breast cancer refers to breast cancer with a genetic susceptibility gene.PTEN germline mutations are rare in breast cancer,but patients with PTEN mutations have a high risk of breast cancer.In 2021,A young patient with bilateral breast cancer was admitted to the Obstetrics and Gynecology Hospital,Fudan University.Due to bilateral multiple breast lumps,she underwent Vacuum-Assisted Breast Biopsy,which was pathologically confirmed as right ductal carcinoma in situ,left breast invasive carcinoma.The patient had multiple neoplasms in bilateral axillary region skin,neck skin and bilateral inguinal regiona skin,and the second-generation sequencing results of peripheral blood genes showed PTEN gene mutation.Combined with family history,the patient was diagnosed with Cowden syndrome(CS).Such patients should be paid attention to cancer risk management and family management,so as to attain early diagnosis and treatment.

Prostate cancer(PCa)is currently the second most common malignancy in men worldwide,and its incidence rate is on the rise.Most cases of PCa are treated by radical prostatectomy,but with the development of medical imaging and innovation in therapeutic theories and technology,focal therapy has shown better application prospects in the treatment of PCa.Compared with radi-cal prostatectomy,focal therapy yields satisfactory results in terms of effectiveness and reduction of complications in addition to avoid-ance of overtreatment and treatment-related financial burden.This article reviews the strategies of focal therapy for PCa,including cryo-ablation,high-intensity focused ultrasound,irreversible electroporation,and photodynamic therapy,with an analysis of the clinical tri-als in recent years.

Studies have shown that a variety of diseases such as cardiovascular disease, renal disease and cancer are closely related to trimethylamine oxide (TMAO). Clinically, abnormal elevation of TMAO has been used as an evaluation index of atherosclerosis (AS) prior to imaging. In this study, we investigated the effects of lipid metabolism disorders as well as pharmacological interventions on urinary TMAO using a hyperlipidemic golden gopher model. The study used 48 Syrian golden hamster modeled with a high-fat diet for 2 weeks, and then ezetimibe, simvastatin, ezetimibe and simvastatin groups were administered for 4 consecutive weeks, as well as the clinical trial drug, IMM-H007, for pharmacological intervention. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: SCXK (Beijing) 2021-0011). Urine from rats was analyzed for 2D band selective heteronuclear single quantum coherence (2D bs-HSQC) at week 2 and 4 after drug administration. The results indicated that, in comparison to the control group, the high-fat diet significantly elevated urinary TMAO levels in the model group of hamsters after both 2 and 4 weeks of treatment (P < 0.05). Urinary TMAO levels were significantly reduced (P < 0.05) in the model group after 2 or 4 weeks of intervention with ezetimibe, simvastatin, combination therapy, and IMM-H007, showing a marked decrease even after 2 weeks of treatment. The detection of TMAO could precede the measurement of serum biochemical indicators, facilitating earlier efficacy assessment. This study evaluated the modulatory effects of clinical drugs and clinical trial drugs on TMAO, which provides useful information for clinical drug use and drug research. It also provides a means of TMAO detection based on 2D NMR technology, which is helpful for the clinical application of TMAO detection index.