Objective:To investigate the construction of fluorinated human serum albumin (F-HSA) nanoparticles loaded with epirubicin (EPI) EPI@F-HSA and its potential in urothelium penetration after bladder perfusion in female C57 mice.Methods:From January 2023 to December 2023, HSA and EPI were selected as raw materials to synthesize albumin nanoparticles loaded with EPI (EPI@HSA) based on the principles of biomineralization. EPI@F-HSA was synthesized through an amide reaction. The molecular descriptor of hydrated particles were measured by dynamic light scattering and potentiometric analyzer, and the release curve of EPI in vitro was plotted at 0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48 h. The inhibitory effect of EPI@HSA and EPI@F-HSA nanoparticles on MB49 tumor cell activity was determined by MTT assay. The fluorescence distribution of EPI in mouse bladder sections after drug infusion was recorded by confocal microscope and the difference of fluorescence density of EPI was examined by Tukey post-hoc test to reflect the urothelium permeability.Results:The average hydrated particle sizes of EPI@HSA and EPI@F-HSA were 28.2 nm and 32.7 nm, respectively, and the polydispersity index (PDI) were 0.102 and 0.154. The cumulative EPI release of EPI@HSA and EPI@F-HSA nanoparticles within 12 h were 60.5% and 58.2% respectively in pH 5.0 buffer solution, and were 32.8% and 27.1% in pH 7.4 buffer solution. The median inhibitory concentrations of EPI@HSA and EPI@F-HSA nanoparticles on MB49 bladder cancer cells were 1.848 μmol/L and 1.650 μmol/L respectively. After perfusion with EPI, EPI@HSA, and EPI@F-HSA, the fluorescence intensities of EPI in the bladder wall were 2.63±0.43, 3.22±0.20 and 8.71±0.70, respectively, and the EPI fluorescence intensity of EPI@F-HSA was significantly higher than that of EPI@HSA ( P<0.01) and free EPI ( P<0.01). Conclusions:The fluorinated albumin nanoparticles had uniform particle size, good stability, significant inhibition of tumor cell activity and osmotic potential in urothelium, which had the potential to improve the anti-tumor efficacy and were expected to become a new drug delivery system targeting bladder cancer.

Objective:To investigate the construction of fluorinated human serum albumin (F-HSA) nanoparticles loaded with epirubicin (EPI) EPI@F-HSA and its potential in urothelium penetration after bladder perfusion in female C57 mice.Methods:From January 2023 to December 2023, HSA and EPI were selected as raw materials to synthesize albumin nanoparticles loaded with EPI (EPI@HSA) based on the principles of biomineralization. EPI@F-HSA was synthesized through an amide reaction. The molecular descriptor of hydrated particles were measured by dynamic light scattering and potentiometric analyzer, and the release curve of EPI in vitro was plotted at 0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48 h. The inhibitory effect of EPI@HSA and EPI@F-HSA nanoparticles on MB49 tumor cell activity was determined by MTT assay. The fluorescence distribution of EPI in mouse bladder sections after drug infusion was recorded by confocal microscope and the difference of fluorescence density of EPI was examined by Tukey post-hoc test to reflect the urothelium permeability.Results:The average hydrated particle sizes of EPI@HSA and EPI@F-HSA were 28.2 nm and 32.7 nm, respectively, and the polydispersity index (PDI) were 0.102 and 0.154. The cumulative EPI release of EPI@HSA and EPI@F-HSA nanoparticles within 12 h were 60.5% and 58.2% respectively in pH 5.0 buffer solution, and were 32.8% and 27.1% in pH 7.4 buffer solution. The median inhibitory concentrations of EPI@HSA and EPI@F-HSA nanoparticles on MB49 bladder cancer cells were 1.848 μmol/L and 1.650 μmol/L respectively. After perfusion with EPI, EPI@HSA, and EPI@F-HSA, the fluorescence intensities of EPI in the bladder wall were 2.63±0.43, 3.22±0.20 and 8.71±0.70, respectively, and the EPI fluorescence intensity of EPI@F-HSA was significantly higher than that of EPI@HSA ( P<0.01) and free EPI ( P<0.01). Conclusions:The fluorinated albumin nanoparticles had uniform particle size, good stability, significant inhibition of tumor cell activity and osmotic potential in urothelium, which had the potential to improve the anti-tumor efficacy and were expected to become a new drug delivery system targeting bladder cancer.

BACKGROUND:Some patients still have unsatisfactory improvement of operative limb fatigue and pain after total knee arthroplasty.Clinical findings show that Jianpi Yiqi Huoxue Formula can promote recovery after total knee arthroplasty,but the specific efficacy remains to be studied. OBJECTIVE:To observe the effect of Jianpi Yiqi Huoxue Formula on the muscle strength and pain of the operated limb after the primary unilateral total knee arthroplasty. METHODS:A total of 74 patients undergoing primary unilateral total knee arthroplasty were randomly divided into a trial group and a control group with 37 patients in each group.All patients received the same prostheses and surgical methods during the operation.Patients in the control group were treated with routine analgesics,anticoagulant drugs and functional exercise after the operation.The trial group received Jianpi Yiqi Huoxue Formula after the treatment in the control group.Both groups were treated continuously and followed up for 1 month.The changes in isokinetic muscle strength(peak torque and total work amount of extensor and flexor),visual analog scale score and the hospital for special surgery score of the two groups were analyzed. RESULTS AND CONCLUSION:(1)The trial group had better improvement in peak torque and total work amount of extensor and flexor and the hospital for special surgery score than the control group 14 days and 1 month after surgery(P<0.05).(2)In contrast to the control group,the visual analog scale score of the trial group improved better at 7 and 14 days and 1 month after surgery(P<0.05).(3)It is indicated that Jianpi Yiqi Huoxue Formula can effectively improve the muscle strength of the operated limb,enhance the degree of postoperative joint pain,and promote functional rehabilitation after total knee arthroplasty.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*

Fiber photometry is a recently-developed method that indirectly measures neural activity by monitoring Ca

The orbitofrontal cortex (OFC) is involved in diverse brain functions via its extensive projections to multiple target regions. There is a growing understanding of the overall outputs of the OFC at the population level, but reports of the projection patterns of individual OFC neurons across different cortical layers remain rare. Here, by combining neuronal sparse and bright labeling with a whole-brain florescence imaging system (fMOST), we obtained an uninterrupted three-dimensional whole-brain dataset and achieved the full morphological reconstruction of 25 OFC pyramidal neurons. We compared the whole-brain projection targets of these individual OFC neurons in different cortical layers as well as in the same cortical layer. We found cortical layer-dependent projections characterized by divergent patterns for information delivery. Our study not only provides a structural basis for understanding the principles of laminar organizations in the OFC, but also provides clues for future functional and behavioral studies on OFC pyramidal neurons.

The olfactory bulb (OB) is the first relay station in the olfactory system. In the OB, mitral/tufted cells (M/Ts), which are the main output neurons, play important roles in the processing and representation of odor information. Recent studies focusing on the function of M/Ts at the single-cell level in awake behaving mice have demonstrated that odor-evoked firing of single M/Ts displays transient/long-term plasticity during learning. Here, we tested whether the neural activity of M/Ts and sniffing patterns are dependent on anticipation and reward in awake behaving mice. We used an odor discrimination task combined with in vivo electrophysiological recordings in awake, head-fixed mice, and found that, while learning induced plasticity of spikes and beta oscillations during odor sampling, we also found plasticity of spikes, beta oscillation, sniffing pattern, and coherence between sniffing and theta oscillations during the periods of anticipation and/or reward. These results indicate that the activity of M/Ts plays important roles not only in odor representation but also in salience-related events such as anticipation and reward.

Objective: To study the feasibility, safety and aesthetics of laparoscopic cholecystectomy using a single-port through the umbilicus in patients with chronic cholecystitis with cholecystolithiasis. Methods: From Jan 2007 to Jun 2017, the clinical data of 4790 patients who underwent single-port, 4 426 patients conventional three-ports, and 3 304 patients two-ports laparoscopic cholecystectomy were retrospectively studied. Results: There were no death in all the three groups. There were no significant differences in the incidences of postoperative bleeding, bile leakage, biliary tract injury and other significant short-term complications (all P>0.05). The operation time of transumbilical single-port laparoscopic cholecystectomy was significantly longer than that of two-ports and three-ports laparoscopic cholecystectomy [(35.3±9.0)min vs. (28.4±7.2)min vs. (23.3±6.4)min, P<0.05]. Looking only in a single year, there was no significant difference in the operation time of the three groups in the year 2017 (P>0.05). There were no significant differences among the three groups in intraoperative blood loss, first postoperative passing of flatus, postoperative pain, and length of hospital stay (all P>0.05). The satisfaction score of surgical scar in the single-port group was higher than that in the two-ports and three-ports groups [(9.6±1.6) vs. (7.6±1.9) vs. (6.7±2.0), P<0.05]. Conclusions Transumbilical single-port laparoscopic cholecystectomy was safe and feasible, with good aesthetics and other advantages. It was more difficult than the traditional laparoscopic technique. After the learning curve, the operation time could be comparable to the three-ports technique.

Objective To investigate the regularity and predictors of weight loss during concurrent chemo-radiotherapy for nasopharyngeal carcinoma patients. Methods A retrospective study was carried out on 82 patients with nasopharyngeal carcinoma ,with average age of 45 years ,who received concurrent chemoradiotherapy at the Affiliated Cancer Hospital of Guangzhou Medical University. Paired t-test was used to analyze the weight loss pattern during chemoradiotherapy. The Spearman′s rank correlation analysis was used to investigate the correlation between high weight loss(HWL)and the clinical factors. Results The paired t-test showed that the weight of the patients decreased continuously every week during chemoradiotherapy(P < 0.05),and the value dropped most significantly during the 4th week. Among these 82 patients,32 were determined as HWL(weight loss > 10%). Spearman′s rank correlation analysis showed that HWL was associated with older age,female,higher T and TNM stage,3D-CRT technology,the higher dose of radiotherapy in nasopharynx and in neck lymph node,and decreases of leukopenia and hemoglobin over degree Ⅱ(P<0.05). Conlousions Weight may decrease continuously every week during chemoradiotherapy for nasopharyngeal carcinoma patients. Age,gender,T stage,TNM stage,radio-therapy dose,and leukopenia and hemoglobin decreases may be predictors for weight loss degree during concurrent chemoradiotherapy for nasopharyngeal carcinoma patients.

Objective To investigate the organ function survival and late effects and secondary malignancy of childhood neuroblastoma (NB) with high intensity comprehensive treatment.Methods A total of 23 children with NB who received comprehensive treatment in Shanghai Children's Medical Center from December 1998 to October 2010 were enrolled.All tests were formulated according to the Children's Oncology Group (COG)'s guidelines with the approval of parents.The late side effects were graded by CTCAE v3.0,and hearing loss related to platinum was graded by Brock and Chang.Results The median follow-up was 96 (65-170) months.All the patients had at least one late side effect.The occurrence rate of 1-2 adverse effects was 100％,and 17.4％ (4/23 cases) of patients had grade 3-4 adverse effects.90.5％ of children (19/21 cases)developed hearing loss on both sides.Eleven children (52.4％,11/21 cases) developed dental abnormities,comprising microdontia,missing teeth,root stunting and enamel hypoplasia.9.5％ of children (2/12 cases) had scoliosis.42.8％ of children (9/12 cases) developed hypogonadism with the approval of parents or delayed growth.47.4％ of children (9/19 cases) had abnormal respiratory function.36.8％ of children (7/19 cases)had abnormal cardiac function.33.4％ of children (7/21 cases)developed renal damage.23.8 ％ of children (5/21 cases) had abnormal liver function.66.7％ of children (14/21 cases) had low level of cortisol,but adrenocorticotrophic hormone was normal.All children had normal function of thyroid.Three children developed secondary malignancy:leukemia,malignant fibroma and liver tumor.Conclusions The incidence of long-term adverse reactions of patients with neuroblastoma treated with high intensity comprehensive treatment is very high and the patients may have adverse effects,like hearing loss,dental abnormality,cardiopulmonary function abnormality,musculoskeletal problems and secondary malignancy.The upmost importance is to establish long-term follow-up program to detect the life quality of children and amend current therapeutic schemes improve life quality.