ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.

ObjectiveTo observe the prevention and control effect of processed Polygonatum cyrtonema on depression induced by chronic unpredictable mild stress （CUMS） in female rats. MethodsForty rats were assigned into control， model， and low-， medium-， and high-dose processed P. cyrtonema groups according to the random number table method， with 8 rats in each group. The rat model of depression was established with the CUMS method. The body mass， open field test， forced swimming test， Morris water maze test， levels of neurotransmitters ［dopamine （DA）， 5-hydroxytryptamine （5-TH）， and acetylcholine （ACh）］， serum levels of sex hormones ［gonadotropin-releasing hormone（GnRH）， testosterone （T）， and estradiol （E₂）］ and inflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-10］， and mRNA and protein levels of factors in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TRKB）/cAMP-response element binding protein （CREB） pathway were employed to evaluate the effect of processed P. cyrtonema on the CUMS-induced depression in female rats. ResultsThe body mass， open field test results， and forced swimming test results showed that the rat model of depression was successfully established. The comparison of behaviors， neurotransmitters， sex hormones， inflammatory factors， and neural pathways among groups showed that processed P. cyrtonema had different effects of preventing the development of depression in female rats. SPSS 25 was used for statistical analysis of error and significance. T test was conducted between groups. Each treatment group showed significant therapeutic effect compared with the model group （P<0.05）. Processed P. cyrtonema elevated the level of 5-TH （P<0.01） and lowered the levels of DA and ACh （P<0.01） in the brain tissue of female rats. In addition， it reduced the serum levels of GnRH， T， E₂， TNF-α， and IL-6 （P<0.05） and up-regulated the mRNA levels of BDNF and TRKB in the rat brain. ConclusionProcessed P. cyrtonema has a non-hyperactive preventive effect on CUMS-induced depression in rats， which provides a theoretical basis for the development of processed P. cyrtonema as a functional food product.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

Objective    To compare the differences of clinical effects between the bilateral endoscopic breast reconstruction and the open breast reconstruction. Methods    The clinical data of 28 female patients who underwent bilateral breast graft reconstruction in the Department of Breast Surgery of West China Hospital from January 2017 to January 2021 were analyzed retrospectively. The patients were divided into two groups: an endoscopic group (n=12, aged 41.3±8.9 years) and an open group (n=16, aged 41.6±8.8 years). The clinical data of the two groups of patients were compared. Results     There was no significant difference in demographic and oncological data between the two groups (P>0.05). There was a significant difference in the implants between the two groups (P=0.008). The operation time (298.2±108.6 min vs. 326.5±95.8 min, P=0.480) and anesthesia time (373.4±91.2 min vs. 400.3±97.1 min, P=0.463) were not significantly different. The total complications (P=0.035) and major complications (P=0.024) in the open group were more than those in the endoscopic group. For the comparison of breast satisfaction, psychosocial well-being and sexual well-being, the scores at six months and one year after surgery were higher in the endoscopic group than those in the open group (P<0.05). Conclusion    The endoscopic reconstruction is safe and effective, with high satisfaction rates regarding  breast reconstruction and quality of life, and is superior to conventional open surgery.

Objective This study was conducted to assess the accuracy of [18F] fiuorodeoxyglucose-positron emission tomography/computed tomography (18FDG PET-CT) in detection of pelvic nodal metastases in endometrial cancer.Methods Patients with endometrial cancer from January 2015 to June 2017 confirmed by the postoperative pathology were retrospectively analyzed.30 patients finished PET-CT before operation.The findings on histopathology were compared with 18FDG-PET/CT findings to calculate the sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV),and accuracy of 18FDG-PET/CT.To analyze the efficacy of maximum standardized uptake (SUVmax) and lymph node maximum standardized uptake (LN-SUVmax) of PET-CT in the diagnosis of pelvic lymph node metastasis.Resuits For detection of pelvic nodes,based on patient analysis,18FDG-PET/CT had a sensitivity of 75.0％,specificity of 88.5％,PPV of 50.0％,NPV of 95.8％ and accuracy of 86.7％.Based on a nodal region analysis,18FDG-PET/CT had a sensitivity of 83.3％,specificity of 98.3％,PPV of 55.0％,NPV of 99.6％,and accuracy of 98.3％.When maximum standardized uptake values (SUVmax) ＞ 8,area under curve (AUC) =0.64,Yonden Index =0.42.When maximum standardized uptake values of lymphonodus (LN-SUVmax) ＞ 3 (AUC =0.79,Yonden Index =0.63),the sensitivity and specificity of diagnosis of lymph node metastasis were 100％,42.31％,and 75.0％,88.5％,but without statistically significant difference.Although AUC of LN-SUVmax was higher than SUVmax of primary lesion,but the difference was not statistically significant (P ＞ 0.05).Conclusions 18 FDG-PET/CT has high specificity,NPV for detection of pelvic LN metastasis area in endometrial cancer,which can provide preoperative basis for patients with endometrial cancer to avoid lymph node resection,thereby reducing the risk of early endometrial cancer surgery and improving the quality of life after surgery.We concluded that,there were no exact cutoffs of SUVmax for the prediction of lymph node metastases,neither primary lesion,nor lymph node.There is clearly a need for multicenter,large-scale trials to find out better parameters in judging metastasis of lymphnodes.

OBJECTIVE: To summarize the clinical characteristics and identify gene mutations of 2 probands with Rubinstein-Taybi syndrome (RSTS). METHODS: Clinical characteristics of 2 probands with Rubinstein-Taybi syndrome were summarized. Genomic DNA was extracted from peripheral blood samples from the patients and their parents. Genomic DNA was subjected to whole exome next generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The two patients were characterized by typical facial features, broad thumbs and big toes, intellectual disability, and postnatal growth retardation. Two variants of the CREBBP gene, namely c.3779+1G>A and c.5052_c.5053insT, were respectively identified in the 2 patients. Among these, c.3779+1G>A was a previously known pathological mutation, while c.5052_c.5053insT was unreported previously. Both variants were predicted to be pathological. CONCLUSION Two cases of Rubinstein-Taybi syndrome were diagnosed, which facilitated the diagnosis and genetic counselling.
CREB-Binding Protein ; genetics ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Phenotype ; Rubinstein-Taybi Syndrome ; genetics

OBJECTIVE: To explore the analgesic mechanism of intrathecal trichostatin A (TSA) injection in a rat model of neuropathic pain induced by chronic constrictive injury (CCI). METHODS: Male SD rats were randomized into sham operation+ DMSO group (group S), CCI +DMSO group (group C), CCI +10 μg TSA group (group T), and in the latter two groups, rat models of neuropathic pain were established induced by CCI. The rats were given intrathecal injections of 10 μL 5% DMSO or 10 μg TSA (in 5% DMSO) once a day on days 7 to 9 after CCI or sham operation. The rats were euthanized after behavioral tests on day 10, and the lumbar segment of the spinal cord was sampled to determine the expression of histone deacetylase 4 (HDAC4) protein and mRNA and detect the differentially expressed miRNAs using a miRNA chip. MiR-190b-5p and miR-142-3p were selected for validation of the results using RT-qPCR. RESULTS: Compared with those in group S, the rats in group C showed significantly decreased paw withdrawal mechanical threshold (PWMT) from day 3 to day 10 after CCI ( < 0.05); intrathecal injection of TSA significantly reversed the reduction of PWMT following CCI ( < 0.05). Positive HDAC4 expression was detected mainly in the cytoplasm of the neurons in the gray matter of the spinal cord, and was obviously up-regulated after CCI ( < 0.05). Intrathecal injection of TSA significantly suppressed CCI-induced up-regulation of HDAC4 at 10 days after the operation ( < 0.05). Compared with the miRNA profile in group S, miRNA profiling identified 83 differentially expressed miRNAs in group C (fold change ≥2 or ≤0.5, < 0.05); TSA treatment reversed the expressions of 58 of the differentially expressed miRNAs following CCI, including 41 miRNAs that were decreased after CCI but up-regulated following TSA treatment. The results of real-time PCR validated the changes in the expressions of miR-190b-5p and miR-142-3p. CONCLUSIONS TSA suppresses CCI-induced up-regulation of HDAC4 and reverses differential expressions of miRNAs in the spinal cord of rats, which may contribute to the analgesic effect of TSA on neuropathic pain.
Animals ; Histone Deacetylases ; Hydroxamic Acids ; Male ; MicroRNAs ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; Up-Regulation

Objective: To summarize the clinical characteristics and identify gene mutations of 2 probands with Rubinstein-Taybi syndrome (RSTS). Methods: Clinical characteristics of 2 probands with Rubinstein-Taybi syndrome were summarized. Genomic DNA was extracted from peripheral blood samples from the patients and their parents. Genomic DNA was subjected to whole exome next generation sequencing. Suspected variants were confirmed by Sanger sequencing. Results: The two patients were characterized by typical facial features, broad thumbs and big toes, intellectual disability, and postnatal growth retardation. Two variants of the CREBBP gene, namely c. 3779+ 1G>A and c. 5052_c.5053insT, were respectively identified in the 2 patients. Among these, c. 3779+ 1G>A was a previously known pathological mutation, while c. 5052_c.5053insT was unreported previously. Both variants were predicted to be pathological. Conclusion Two cases of Rubinstein-Taybi syndrome were diagnosed, which facilitated the diagnosis and genetic counselling.

Objective:To investigate the expression of Leucine-rich repeat-containing G protein-coupled receptor 5(LGR5) in endometrial cancer(EC) and their relationship with clinicopathological characteristics.Methods:Immunohistochemistry were performed to measure the LGR5 expression in EC(n =90) and normal endometrium tissue(n =30).The expression of LGR5 and its relationship with clinicopathological characteristics were analyzed.Results:The expression of LGR5 was significantly higher in EC than that in normal tissue (63.3％ vs 23.3％,P＜0.001).The expression of LGR5 in ＜ 1/2 myometrium infiltration group was higher than in ≥1/2 myometrium infiltration group(72.5％ vs 33.3％,P =0.001).There was no significant difference between the expression of LGR5 in different group of age,histological type,histological differentiation,cervical stroma invasion,lymph node metastasis,FIGO stage(P ＞ 0.05).Multivariate analysis showed that LGR5 was an independent influential factor of myometrium infiltration (OR =0.163,95％ CI 0.034 ～ 0.772,P =0.022).Conclusions:LGR5 is up-regulated in EC,and is correlated to myometrium infiltration.LGR5 may play an important role in EC tumorigenesis.