ObjectiveTo establish a castrated male mouse model and to preliminarily investigate the effects of testosterone replacement therapy （TRT） on behavior， serum indices， and histopathological changes in castrated mice， as well as to explore the role of androgens in cognitive function. MethodsForty 6-month-old male C57/BL6J mice were randomly divided into sham operation group， castration group， testosterone propionate （0.5，1.0 mg/kg） treated group， with 10 mice in each group. Following castration and subcutaneous administration of testosterone propionate at different doses （0.5 and 1.0 mg/kg） for TRT， learning and memory abilities were assessed using the Morris water maze （MWM） test and the passive avoidance test. Serum testosterone and serum brain-derived neurotrophic factor （BDNF） levels were measured by ELISA， and histopathological changes in the hippocampus were examined using hematoxylin-eosin （HE） staining. ResultsRoutine observations： there were no statistically significant differences in body weight among groups at any time point. MWM test： compared with castration group， sham operation group and testosterone propionate-treated groups （0.5， 1.0 mg/kg） showed significantly reduced escape latency on days 4 and 5 （P0.05）， while the number of platform crossings and the time spent in the target quadrant significantly increased （P0.05）. Passive avoidance test： the number of passive avoidance errors significantly decreased in sham operation group and testosterone propionate （1.0 mg/kg）-treated group （P0.05）， and the passive avoidance latency was significantly prolonged in sham-operated group and testosterone propionate-treated groups （0.5， 1.0 mg/kg） （P0.05）. Serum testosterone and serum BDNF assays： serum testosterone levels and serum BDNF concentrations significantly increased in sham operation group and testosterone propionate-treated groups （0.5， 1.0 mg/kg） （P0.01）. HE staining： compared with sham operation group， neuronal density in all hippocampal subregions was slightly reduced in castration group； in the testosterone propionate （0.5 mg/kg）-treated group， neuronal arrangement in the CA1 and CA3 regions was improved and apoptotic cells were reduced compared with castration group； in testosterone propionate （1.0 mg/kg）-treated group， the pyramidal cell layer in the CA3 region was more compactly arranged， with fewer apoptotic cells than in castration group. ConclusionTRT improves learning and memory performance in castration male mice， potentially through modulation of hippocampal BDNF signaling pathways.

Objective:To analyze factors influencing the melasma severity, and to evaluate the efficacy of different treatment modalities.Methods:A retrospective analysis was conducted on clinical data from patients diagnosed with melasma at the Pigmentary Disorders Specialty Clinic in the Department of Dermatology, Huashan Hospital, Fudan University from July 2018 to December 2023. Patients' Fitzpatrick skin types, lesion color, locations and subtypes were evaluated by dermatologists, the melasma area and severity index (MASI) scores were calculated, and ΔMASI scores (baseline MASI scores - post-treatment MASI scores) were used for efficacy evaluation. The t test and one-way analysis of variance were used to analyze factors influencing the severity of melasma, the paired t test was used to analyze the differences in MASI scores before and after treatment, and a multivariate linear regression model was established to analyze factors influencing the efficacy in the treatment of melasma. Results:A total of 254 patients (including 249 females, 98.0%) with melasma were included, with ages of 40.8 ± 6.1 years. The Fitzpatrick skin type was Ⅲ in 213 (83.9%) patients, and Ⅳ in 41 (16.1%) patients; 180 (70.9%) patients lacked the habit of using sunscreens regularly. According to the location of pigment deposition, 166 cases (65.4%) were classified as epidermal type, and 88 (34.6%) as mixed type. Pigmented lesions were located on the cheek (174 cases, 68.5%), midface (26 cases, 10.2%), or lower jaw (54 cases, 21.3%), with periorbital involvement observed in 127 cases (50.0%). Before treatment, baseline MASI scores were significantly higher in the skin type Ⅳ group (19.75 ± 5.08) than in the skin type Ⅲ group (14.47 ± 4.18, P < 0.001), in the non-sunscreen users (16.45 ± 4.61) than in the sunscreen users (12.59 ± 3.91, P < 0.001), in the epidermal type group (15.99 ± 4.82) than in the mixed type group (14.07 ± 4.35, P < 0.001), in the mandibular type group (18.37 ± 5.14) than in the midfacial type group (14.23 ± 3.46, P < 0.001) and malar type group (14.54 ± 4.40, P < 0.001), as well as in the patients with periorbital involvement (16.54 ± 4.90) than in those without (14.10 ± 4.26, P < 0.001). According to the main treatment regimens, the patients were divided into the topical 2% hydroquinone group (109 cases, topically treated with 2% hydroquinone cream nightly), topical non-hydroquinone skin-lightening agents group (36 cases, topically treated with non-hydroquinone skin-lightening or exfoliating agents), oral tranexamic acid group (50 cases, treated with oral tranexamic acid 250 mg twice daily), and alpha hydroxy acid (AHA) chemical peeling group (30 cases, receiving AHA chemical peeling treatment monthly with the AHA concentration escalating from 20% to 50%). After treatment, MASI scores were significantly reduced from baseline in all the 4 groups (all P < 0.001), and the ΔMASI values significantly differed among the topical 2% hydroquinone group, topical non-hydroquinone skin-lightening agents group, oral tranexamic acid group, and AHA chemical peeling group (1.65 ± 2.19, 1.40 ± 2.16, 4.58 ± 3.09, 3.39 ± 3.61, respectively, F = 17.40, P < 0.001). The oral tranexamic acid group and AHA chemical peeling group showed significantly superior efficacy compared to the topical 2% hydroquinone group and topical non-hydroquinone skin-lightening agents group (all P < 0.05), while there was no significant difference in the efficacy between the oral tranexamic acid group and the AHA chemical peeling group ( P > 0.05). After adjustment for potential confounders in the multivariate linear regression model, the oral tranexamic acid group (β = 2.64) and AHA chemical peeling group (β = 1.55) still showed significantly superior efficacy compared to the topical 2% hydroquinone group (both P < 0.05) ; the skin type Ⅳ group exhibited significantly superior efficacy compared to the skin type Ⅲ group (β = 1.87, P < 0.001) . Conclusions:Dark skin color, lack of sun protection habits, epidermal melasma, and mandibular-type melasma, and periorbital involvement were associated factors for the severity of melasma. Oral tranexamic acid and AHA chemical peeling appeared to exhibit superior efficacy compared to topical 2% hydroquinone cream and topical non-hydroquinone skin-lightening agents.

Objective:To explore the development process of family resilience in children with congenital pseudarthrosis of the tibia (CPT) and to understand the long-term challenges and coping strategies that CPT imposes on the families of affected children.Methods:This study combined purposive sampling and theoretical sampling. It selected 15 caregivers of CPT children from Hunan Children's Hospital for semi-structured interviews. Grounded theory was used to analyze the interview results.Results:The development of family resilience in CPT children's families occurred in three stages: pre-formation stage, formation stage, and maintenance stage. In facing negative emotions and family challenges, caregivers first needed to rebuild their inner beliefs. They then adjusted the family organizational model, adopted open and inclusive communication, and actively sought external support to foster the development of family resilience. Ultimately, caregivers were able to self-regulate their emotions, accumulate caregiving experience, and begin to shift their life perspective.Conclusions:The development of family resilience in CPT children's families is a dynamic, multi-stage process with interactions of multiple factors. Healthcare providers should offer professional health guidance according to the different stages of family development. Moreover, the government and schools should increase their attention and support, working together with families and healthcare providers to enhance family resilience for children with CPT.

To explore the impacts of TGR5 on liver lipid metabolism and bile acid synthesis in dairy cows with fatty liver.Liver tissues of healthy cows and cows with fatty liver were collected through puncture technique.The protein and mRNA expressions of lipid synthesis-related factors ACC1,FAS,SREBF1,lipid oxidation factor CPT1A,and bile acid synthesis-related factors CYP8B1,CYP7B1,CYP27A1 were detected by Western blot and fluorescent quantitative PCR.Moreover,the mRNA levels of CYP7B1 were determined.Primary hepatocytes of 1-day-old calves were extracted and cultured in vitro,and four treatment groups were established,namely Control,NEFA,INT-777,and the INT-777+NEFA group.The concentration of NEFA group was 1.2 mmol/L,the con-centration of INT-777 group was 1 μmol/L,and the concentration of INT-777+NEFA group was 1.2 mmol/L NEFA and 1 μmol/L INT-777 simultaneously.After 12 h of stimulation,cells were collected,and the protein and mRNA levels of ACC1,FAS,SREBF1,CPT1A,CYP8B1,CYP7A1,CYP27A1,and the mRNA levels of CYP7B1 were detected by Western blot and fluorescent quanti-tative PCR.The content of lipid droplets and TG in the cells were detected by flow cytometry and kit.The results demonstrated that compared with healthy cows,the protein and mRNA expressions of ACC1,FAS,SREBF1,CYP8B1,and CYP7A1 in the liver tissues of fatty liver cows were upreg-ulated,while the protein and mRNA levels of CPT1 A,CYP27A1,TGR5,and the mRNA levels of CYP7B1 were downregulated.In vitro experiments revealed that compared with the Control group,the protein and mRNA levels of ACC1,FAS,SREBF1,CYP8B1,and CYP7A1 in the NEFA group were upregulated,and the protein and mRNA levels of CPT1A,CYP27A1,and TGR5,as well as the mRNA level of CYP7B1,were downregulated.Compared with the NEFA group,the protein and mRNA levels of ACC1,FAS,SREBF1,CYP8B1,CYP7A1 were downregulated in the INT-777+NEFA group,while the protein and mRNA levels of CPT1A CYP27A1,and TGR5 as well as the mRNA level of CYP7B1,were upregulated.The results of flow cytometry and the kit indicated that the lipid droplets and TG content in the NEFA group were upregulated compared with the Control group,while the lipid droplets and TG content in the INT-777+NEFA group were downregulated compared with the NEFA group.The above results suggested that the addition of TGR5 agonist promoted the expression of TGR5 and ameliorated the abnormal lipid metabolism and bile acid synthesis in the liver of dairy cows with fatty liver.

To explore the impacts of TGR5 on liver lipid metabolism and bile acid synthesis in dairy cows with fatty liver.Liver tissues of healthy cows and cows with fatty liver were collected through puncture technique.The protein and mRNA expressions of lipid synthesis-related factors ACC1,FAS,SREBF1,lipid oxidation factor CPT1A,and bile acid synthesis-related factors CYP8B1,CYP7B1,CYP27A1 were detected by Western blot and fluorescent quantitative PCR.Moreover,the mRNA levels of CYP7B1 were determined.Primary hepatocytes of 1-day-old calves were extracted and cultured in vitro,and four treatment groups were established,namely Control,NEFA,INT-777,and the INT-777+NEFA group.The concentration of NEFA group was 1.2 mmol/L,the con-centration of INT-777 group was 1 μmol/L,and the concentration of INT-777+NEFA group was 1.2 mmol/L NEFA and 1 μmol/L INT-777 simultaneously.After 12 h of stimulation,cells were collected,and the protein and mRNA levels of ACC1,FAS,SREBF1,CPT1A,CYP8B1,CYP7A1,CYP27A1,and the mRNA levels of CYP7B1 were detected by Western blot and fluorescent quanti-tative PCR.The content of lipid droplets and TG in the cells were detected by flow cytometry and kit.The results demonstrated that compared with healthy cows,the protein and mRNA expressions of ACC1,FAS,SREBF1,CYP8B1,and CYP7A1 in the liver tissues of fatty liver cows were upreg-ulated,while the protein and mRNA levels of CPT1 A,CYP27A1,TGR5,and the mRNA levels of CYP7B1 were downregulated.In vitro experiments revealed that compared with the Control group,the protein and mRNA levels of ACC1,FAS,SREBF1,CYP8B1,and CYP7A1 in the NEFA group were upregulated,and the protein and mRNA levels of CPT1A,CYP27A1,and TGR5,as well as the mRNA level of CYP7B1,were downregulated.Compared with the NEFA group,the protein and mRNA levels of ACC1,FAS,SREBF1,CYP8B1,CYP7A1 were downregulated in the INT-777+NEFA group,while the protein and mRNA levels of CPT1A CYP27A1,and TGR5 as well as the mRNA level of CYP7B1,were upregulated.The results of flow cytometry and the kit indicated that the lipid droplets and TG content in the NEFA group were upregulated compared with the Control group,while the lipid droplets and TG content in the INT-777+NEFA group were downregulated compared with the NEFA group.The above results suggested that the addition of TGR5 agonist promoted the expression of TGR5 and ameliorated the abnormal lipid metabolism and bile acid synthesis in the liver of dairy cows with fatty liver.

Objective To observe the effect of Shaoyao Gancao decoction combined with electroacupuncture on poststroke spasticity in rats.Methods Healthy male Sprague-Dawley(SD)rats were randomly divided into blank group,model group,electroacupuncture group,baclofen group,electroacupuncture combined with high dose of Chinese medicine group,electroacupuncture combined with middle dose of Chinese medicine group,electroacupuncture combined with low dose of Chinese medicine group,high dose of Chinese medicine group,middle dose of Chinese medicine group and low dose of Chinese medicine group,with 10 rats in each group.Open field test and integrated electromyography of quadriceps femoris were tested before modeling and on the 1st,3rd and 6th day after modeling.The samples were taken on day 6.The expression of inflammatory factors in M1 cortex were detected by liquid phase factor technique.The expression of brain-derived neurotrophic factor(BDNF),synaptophysin(SYP),postsynaptic density 95(PSD95),Nestin and β-catenin in M1 cortex was detected by ELISA and Western blot.Results Compared with model group and other intervention groups,the electroacupuncture combined with middle dose of Chinese medicine group make best total distance(P=0.021)and average speed(P=0.021)in open field test on 6th day.make better in integrated electromyography of quadriceps femoris test(P=0.006)on day 3,have higher Ⅱ type fiber ratio,promote IL-10(P=0.006),GMcsf(P=0.045)secretion.ELISA and Western blot also showed that this group behave better in the test of BDNF,SYP,PSD95,Nestin and β-catenin.Conclusion Electroacupuncture combined with Shaoyao-Gancao decoction groups were effective in the treatment of poststroke spasticity in rats,and its mechanism may be to improve the inflammatory environment of the injured site,promote the proliferation of neural stem cells and synaptic regeneration.

Objective:To investigate whether continuous cardiac output (CO) parameters obtained by LiDCO in hemodynamic monitoring of severe patients are consistent with pulse index continuous cardiac output (PiCCO).Methods:From May 18, 2024 to January 10, 2025, 12 critically ill patients who were monitored by PiCCO in the Intensive Care Unit Department of China-Japan Friendship Hospital were prospectively collected. The PiCCO and LiDCO systems were simultaneously connected to the same critically ill patient, injected with ice saline for external calibration, and the average of paired continuous CO measurements were collected. Bland-Altman was used to analyze whether the two were consistent, and Spearman was used to analyze the correlation between norepinephrine dosage and bias.Results:In the data series of 70 pairs, the CO measured by PiCCO was 5.55±1.74, and the CO measured by LiDCO was 4.40(2.90, 6.50), with a bias of 0.52(95% CI: 0.07-0.96) and an upper limit of agreement of 4.2(95% CI: 3.4-4.9), the lower limit of the conformance limit was -3.1(95% CI: -3.9 to -2.4), and the percentage error was 66%, exceeding the clinically acceptable 45%. In the data series where norepinephrine was continuously pumped at the time of data collection, there was a moderate positive correlation between norepinephrine dosage and absolute bias ( r=0.47, P<0.05). There were statistically significant differences in absolute values of bias between groups defined as 0.5 μg/(kg·min) and 1 μg/(kg·min) ( P<0.05). Conclusions:There is no clinically acceptable consistency between LiDCO and PiCCO for continuous CO monitoring in severe patients, and the size of bias may be related to the dosage of norepinephrine.

Objective:To analyze the influencing factors of mood state of common rheumatic (rheumatoid arthritis; systemic lupus erythematosus; ankylosing spondylitis) patients and find out the common characteristics of patients with negative emotions, so as to identify and treat rheumatic patients with anxiety and depression in clinical practice.Methods:A total of 205 patients with rheumatism (83 with rheumatoid arthritis, 74 with systemic lupus erythematosus, 48 with ankylosing spondylitis) admitted to the Shandong Provincial Hospital Affiliated to Shandong University from April to May 2023 were included. The general condition and POMS of patients were collected. All patients were divided into 3 groups of low-TMD/ middle-TMD/ high-TMD(TMD≤90 scores; 90 scores105 scores). The χ2 test was used for categorical variables, and the continuous variables were tested for normal distribution. If they followed a normal distribution, the independent sample t test (for homogeneous variance) or the Welch′s t test (for unequal variance) was used for comparison between the two groups, and one-way analysis of variance was used for comparison between multiple groups; if they did not follow a normal distribution, the Kruskal-Wallis H test was used for comparison between groups. Patients with TMD>90 scores were defined as the negative emotion group. Gender, age, education level, economic income status, and TMD were included in the two-step cluster analysis (TCA) to obtain three cluster groups and analyze the differences between the groups. Logistic regression was used to analyze the risk factors. Results:The study found that patients with rheumatic diseases with low serum albumin levels ( F=6.26, P=0.003), low education level ( χ2=8.36, P=0.015), low economic level ( χ2=15.59, P<0.001), short disease course ( H=28.01, P<0.001), and high disease activity ( χ2=56.93, P<0.001) had higher TMD scores, which was not related to the type of disease ( χ2=4.81, P=0.090). The negative mood group had a higher proportion of females (57.6% vs. 73.4%, χ2=5.16, P=0.023), a shorter course of disease [24(12, 48) months vs. 48(24, 93) months, Z=13.58, P<0.001], and a lower serum albumin [(42.2±4.0) g/L vs. (44.0±3.4)g/L, t=-14.09, P=0.002], low level of education ( χ2=9.04, P=0.029), low level of income ( χ2=10.29, P=0.036), high disease activity ( χ2=61.91, P<0.001). The results of cluster analysis indicated that the above factors were significantly different among the three cluster groups except the course of disease. It is noteworthy that age ( F=19.25, P<0.001) and serum albumin ( F=5.64, P=0.004) had the lowest value and the highest TMD score ( F=5.64, P<0.001). Regression analysis showed that gender, disease course and disease activity were related factors to the occurrence of negative emotions, and high disease activity was a risk factor [ OR(95% CI) =26.58(4.53, 156.09), P<0.001]. Men [ OR(95% CI)=0.20 (0.08, 0.50), P=0.001) and the course of [ OR(95% CI)=0.99 (0.98, 1.00), P=0.007) as the protective factors. Conclusion:Male, serum albumin level, education level, income level, disease course and disease activity were the main factors affecting the mood state of patients with rheumatism, in which high disease activity was the risk factor, male and long disease course were the protective factors.

Objective:To analyze factors influencing the melasma severity, and to evaluate the efficacy of different treatment modalities.Methods:A retrospective analysis was conducted on clinical data from patients diagnosed with melasma at the Pigmentary Disorders Specialty Clinic in the Department of Dermatology, Huashan Hospital, Fudan University from July 2018 to December 2023. Patients' Fitzpatrick skin types, lesion color, locations and subtypes were evaluated by dermatologists, the melasma area and severity index (MASI) scores were calculated, and ΔMASI scores (baseline MASI scores - post-treatment MASI scores) were used for efficacy evaluation. The t test and one-way analysis of variance were used to analyze factors influencing the severity of melasma, the paired t test was used to analyze the differences in MASI scores before and after treatment, and a multivariate linear regression model was established to analyze factors influencing the efficacy in the treatment of melasma. Results:A total of 254 patients (including 249 females, 98.0%) with melasma were included, with ages of 40.8 ± 6.1 years. The Fitzpatrick skin type was Ⅲ in 213 (83.9%) patients, and Ⅳ in 41 (16.1%) patients; 180 (70.9%) patients lacked the habit of using sunscreens regularly. According to the location of pigment deposition, 166 cases (65.4%) were classified as epidermal type, and 88 (34.6%) as mixed type. Pigmented lesions were located on the cheek (174 cases, 68.5%), midface (26 cases, 10.2%), or lower jaw (54 cases, 21.3%), with periorbital involvement observed in 127 cases (50.0%). Before treatment, baseline MASI scores were significantly higher in the skin type Ⅳ group (19.75 ± 5.08) than in the skin type Ⅲ group (14.47 ± 4.18, P < 0.001), in the non-sunscreen users (16.45 ± 4.61) than in the sunscreen users (12.59 ± 3.91, P < 0.001), in the epidermal type group (15.99 ± 4.82) than in the mixed type group (14.07 ± 4.35, P < 0.001), in the mandibular type group (18.37 ± 5.14) than in the midfacial type group (14.23 ± 3.46, P < 0.001) and malar type group (14.54 ± 4.40, P < 0.001), as well as in the patients with periorbital involvement (16.54 ± 4.90) than in those without (14.10 ± 4.26, P < 0.001). According to the main treatment regimens, the patients were divided into the topical 2% hydroquinone group (109 cases, topically treated with 2% hydroquinone cream nightly), topical non-hydroquinone skin-lightening agents group (36 cases, topically treated with non-hydroquinone skin-lightening or exfoliating agents), oral tranexamic acid group (50 cases, treated with oral tranexamic acid 250 mg twice daily), and alpha hydroxy acid (AHA) chemical peeling group (30 cases, receiving AHA chemical peeling treatment monthly with the AHA concentration escalating from 20% to 50%). After treatment, MASI scores were significantly reduced from baseline in all the 4 groups (all P < 0.001), and the ΔMASI values significantly differed among the topical 2% hydroquinone group, topical non-hydroquinone skin-lightening agents group, oral tranexamic acid group, and AHA chemical peeling group (1.65 ± 2.19, 1.40 ± 2.16, 4.58 ± 3.09, 3.39 ± 3.61, respectively, F = 17.40, P < 0.001). The oral tranexamic acid group and AHA chemical peeling group showed significantly superior efficacy compared to the topical 2% hydroquinone group and topical non-hydroquinone skin-lightening agents group (all P < 0.05), while there was no significant difference in the efficacy between the oral tranexamic acid group and the AHA chemical peeling group ( P > 0.05). After adjustment for potential confounders in the multivariate linear regression model, the oral tranexamic acid group (β = 2.64) and AHA chemical peeling group (β = 1.55) still showed significantly superior efficacy compared to the topical 2% hydroquinone group (both P < 0.05) ; the skin type Ⅳ group exhibited significantly superior efficacy compared to the skin type Ⅲ group (β = 1.87, P < 0.001) . Conclusions:Dark skin color, lack of sun protection habits, epidermal melasma, and mandibular-type melasma, and periorbital involvement were associated factors for the severity of melasma. Oral tranexamic acid and AHA chemical peeling appeared to exhibit superior efficacy compared to topical 2% hydroquinone cream and topical non-hydroquinone skin-lightening agents.

Acquired dermal macular hyperpigmentation (ADMH) is a group of diseases clinically characterized by grayish-black macules and patches, with pigment predominantly deposited in the dermis. ADMH includes Riehl's melanosis, lichen planus pigmentosus, and erythema dyschromicum perstans/ashy dermatosis. In light of the remarkable similarities in both morphological and histopathological characteristics among this group of diseases, the academic community has recently proposed the new nosological term "acquired dermal macular hyperpigmentation" to achieve integration and unified classification of these related disorders. This review comprehensively elaborates on advances in the diagnosis and treatment of ADMH, including clinical manifestations, dermoscopic findings, pathological characteristics, and treatment progress.