ObjectiveTo investigate the mechanism of Zuogui Wan （ZGW） in improving ovarian inflammatory microenvironment and stemness of ovarian germline stem cells （OSCs） for treating ovarian aging via the cyclic guanosine monophosphate/adenosine monophosphate synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsForty C57BL/6 female mice were randomly divided into a blank group， a model group， a low-dose ZGW group （2.7 g·kg^-1）， a high-dose ZGW group （5.4 g·kg^-1）， and an estradiol valerate group （0.15 mg·kg^-1）， with 8 mice in each group. Except the blank group， all other groups received a single intraperitoneal injection of cyclophosphamide at 120 mg·kg^-1 to establish an ovarian aging mouse model. After successful modeling， each group was continuously administered for 4 weeks， once daily. The physiological status of the mice was observed， and the ovarian index was calculated. The estrus cycle of the mice was monitored. Hematoxylin-eosin （HE） staining was used to observe pathological changes in ovarian tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum sex hormone levels. Serum inflammatory factors interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and mouse interleukin-6 （IL-6） levels were detected using kits. Western blot was used to detect the protein expression of ovarian cGAS， STING， p-STING， TANK-binding kinase 1 （TBK1）， p-TBK1， interferon-induced transmembrane protein 3 （Fragilis）， and Vasa homolog protein （MVH）. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors in ovarian tissue. Immunofluorescence double labeling was performed to locate OSCs in ovarian tissues， and fluorescence intensities of OSCs markers MVH and octamer binding transcription factor 4 （Oct4） were calculated. ResultsCompared with the blank group， the model group showed reduced body weight， ovarian wet weight， and ovarian index （P<0.01） and a disordered estrus cycle （P<0.01）. In addition， the levels of serum follicle-stimulating hormone （FSH）， TNF-α， IL-6， and IL-1β were increased （P<0.01）， while anti-Müllerian hormone （AMH） and estradiol （E₂） levels were decreased （P<0.01）. The protein expression of cGAS， p-STING/STING， and p-TBK1/TBK1 in ovarian tissue was increased （P<0.05， P<0.01）， while that of OSCs stemness factors MVH and Fragilis was reduced （P<0.01）. Immunofluorescence indicated a reduction in MVH and Oct4 expression in OSCs （P<0.01）. The mRNA expression of inflammatory factors TNF-α， IL-6， and IL-1β in ovarian tissue was increased （P<0.05， P<0.01）. Compared with the model group， the treatment groups exhibited improved body weight， ovarian wet weight， and ovarian index （P<0.05） and a reduced rate of estrus cycle disorder （P<0.05， P<0.01）. The levels of serum FSH， TNF-α， IL-6， and IL-1β were decreased （P<0.05， P<0.01）， while AMH and E₂ levels were increased （P<0.01）. The protein expression levels of cGAS， p-STING/STING， and p-TBK1/TBK1 in ovarian tissue were decreased （P<0.05）， while the protein expression of MVH and Fragilis was increased （P<0.05）， and the fluorescence intensities of MVH and Oct4 were increased （P<0.05， P<0.01）. The mRNA expression of inflammatory factors in ovarian tissue was decreased （P<0.05）. ConclusionZGW alleviate ovarian inflammatory response， regulate ovarian microenvironment homeostasis， and maintain stemness of OSCs in ovarian aging mice probably by modulating the cGAS-STING signaling pathway， thereby improving ovarian function and delaying ovarian aging.

ObjectiveTo explore the therapeutic mechanism of Buchong Tiaojing prescription for rats with diminished ovarian reserve （DOR） from the perspectives of nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） inflammasome and ferroptosis. MethodsA total of 48 female SD rats were randomly divided into a normal group， a model group， low， medium， and high dose groups of Buchong Tiaojing prescription， and an MCC950 group， with eight rats in each group. Except the normal group， all the other groups were injected subcutaneously on the back of the neck with D-galactose to prepare the DOR rat model. From the 15th day of modeling， the rats in the low， medium， and high dose groups of Buchong Tiaojing prescription were subjected to gavage daily at doses of 14.4， 28.8， 57.6 g·kg^-1， respectively. Rats in the MCC950 group were injected intraperitoneally with MCC950 at a dose of 10 mg·kg^-1， once every other day. The interventions of all the groups lasted for 4 weeks. The estrous cycle of the rats was observed with vaginal exfoliated cell smear. Hematoxylin-eosin （HE） staining was performed to observe the development of follicles and corpus luteum in the ovary. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the levels of serum sex hormones and interleukin-1β （IL-1β）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot assay were performed to detect the mRNA and protein expression of NLRP3 inflammasome， acyl-CoA synthetase long-chain family member 4 （ACSL4）， transferrin receptor 1 （TFR1）， and glutathione peroxidase 4 （GPX4）， and oxidative stress kits were used to detect ovarian superoxide dismutase （SOD） and malondialdehyde （MDA） levels. ResultsDuring the experiment， one rat died in the high dose group of Buchong Tiaojing prescription， and a total of 47 rats were finally included in the index tests and statistics. Compared with those in the normal group， rats in the model group had significantly disturbed estrous cycles， increased number of atretic follicles， and significant disorder of serum sex hormones. The mRNA and protein expression of NLRP3 inflammasome， ACSL4， and TFR1 in ovarian tissue was up-regulated （P<0.01）， while that of GPX4 was significantly down-regulated （P<0.01）. The SOD content in the ovary was decreased significantly， while the MDA level was increased （P<0.01）. After drug intervention， the estrous cycle of rats was basically resumed， and the follicles at all levels were more structurally intact and significantly increased in number. Additionally， the levels of serum sex hormones and IL-1β were significantly improved. The mRNA and protein expression of NLRP3 inflammasome， ACSL4， and TFR1 were down-regulated， while that of GPX4 was significantly up-regulated， and the ovarian oxidative stress was alleviated （P<0.05， P<0.01）， especially in the high dose group of Buchong Tiaojing prescription and the MCC950 group. ConclusionInflammatory injury and ferroptosis occur in the ovaries of DOR rats， and the Buchong Tiaojing prescription is able to inhibit ovarian NLRP3 inflammasome， alleviate the degree of ovarian ferroptosis， and improve ovarian reserve.

Objective:To investigate the value of a deep learning model based on diffusion-weighted imaging (DWI) in quick identification of the TOAST etiology classification in patients with acute ischemic stroke (AIS).Methods:In this cross-sectional study, imaging and clinical data of 504 patients with AIS admitted to the First Affiliated Hospital of Xinjiang Medical University from March 2023 to February 2024 were retrospectively reviewed. Using the TOAST etiology classification, there were 252 large artery atherosclerosis type and 252 small-artery occlusion type. The 504 cases were divided into a training set ( n=302), a validation set ( n=101) and a test set ( n=101) using stratified randomization in the ratio of 6∶2∶2. All cases had DWI data. A DenseNet network framework was used to construct DenseNet models by optimizing the model configurations of different layers. Three DenseNet models with different layers (121, 169, 201) were constructed, named DenseNet169 model, DenseNet121 model, and DenseNet201 model. The data enhancement, Adam optimizer and cross-entropy loss function methods were used to improve the convergence speed and robustness of the model, and to balance the positive and negative sample imbalance problem. Independent sample t-test or χ2 was used to compare the clinical data of patients with large artery atherosclerosis type and small-artery occlusion type AIS. Receiver operating characteristic curves and area under the curve (AUC) were performed to evaluate the efficacy of each model in identification of patients with large artery atherosclerosis type and small-artery occlusion type AIS. Results:There were statistically significant differences in age, National Institutes of Health Stroke Scale score at admission, and stenosis or occlusion of large vessels between patients with large artery atherosclerosis type and small-artery occlusion (all P<0.05). In the test set, the AUC, sensitivity, accuracy, and F1 score values of the DenseNet201 model for discriminating patients with large artery atherosclerosis type AIS and small-artery occlusion type AIS (0.826, 0.902, 0.743, 0.780, respectively) were higher than those of DenseNet121 (0.801, 0.647, 0.723, 0.702, respectively) and DenseNet169 model (0.778, 0.882, 0.733, 0.769). Conclusions:The deep learning models based DWI constructed in this study can help with the TOAST etiology classification of AIS cases. DenseNet201 model shows the best and stable performance in the deep learning-based classification.

It has become a consensus that there is a correlation between psoriasis and obesity, but the exact mechanism is not yet clear. Studies demonstrate that common inflammatory pathways and insulin resistance may contribute to the association between psoriasis and obesity. Understanding the impact of obesity on the occurrence and treatment of psoriasis will be beneficial to the treatment of psoriasis.

Objective:To investigate the expression of solute carrier family 35 member E1 (SLC35E1) and SLC35E2B in skin lesions of patients with Mycobacterium infections. Methods:Paraffin-embedded skin tissues of 31 patients confirmedly diagnosed with Mycobacterium infections were collected from Dermatology Hospital of Southern Medical University from 2014 to 2018, including 10 cases of multibacillary leprosy, 9 of nontuberculous mycobacterial infection, 7 of cutaneous tuberculosis, and 5 of erythema induratum. Meanwhile, paraffin-embedded skin tissues of 10 healthy individuals were collected, and served as normal control group. Immunohistochemical staining was performed to determine the expression of SLC35E1 and SLC35E2B in the lesional and normal control skin specimens, and immunofluorescence staining to observe the co-expression of CD68 and S100 with SLC35E1 and SLC35E2B in the skin lesions. Results:Neither SLC35E1 nor SLC35E2B was expressed in the normal control group, but high expression of SLC35E1 and SLC35E2B was observed in the dermis of skin lesions from the patients with leprosy, nontuberculous mycobacterial infection, cutaneous tuberculosis or erythema induratum. Immunohistochemical staining showed that the expression of SLC35E1 and SLC35E2B (expressed as average optical density) was significantly higher in the multibacillary leprosy group (0.143 ± 0.010, 0.169 ± 0.004, respectively) , nontuberculous mycobacterial infection group (0.278 ± 0.015, 0.229 ± 0.088, respectively) , cutaneous tuberculosis group (0.171 ± 0.010, 0.103 ± 0.016, respectively) and erythema induratum group (0.200 ± 0.015, 0.118 ± 0.021, respectively) than in the normal control group (both 0, all P < 0.05) . Immunofluorescence staining showed co-expression of SLC35E1 and SLC35E2B with CD68 in skin lesions of the patients with leprosy, nontuberculous mycobacterial infection, cutaneous tuberculosis. Conclusion:Both SLC35E1 and SLCE2B were markedly highly expressed in skin lesions of patients with Mycobacterium infections.

A case of ichthyosis follicularis,alopecia and photophobia syndrome caused by a novel mutation c.1165C＞T in the membrane-bound transcription factor protease site 2 (MBTPS2) gene was firstly reported.The proband presented with dry skin,congenital hairlessness,follicular keratotic papules,photophobia,epilepsy,and mental and motor retardation.Next-generation and Sanger sequencing analysis confirmed that the proband and his mother both had a c.1165C＞T (p.pro389Ser) mutation in exon 9 of the MBTPS2 gene.According to the clinical manifestations of the patient and genetic characteristics of the MBTPS2 gene mutation,the patient was diagnosed with ichthyosis follicularis,alopecia and photophobia syndrome.

Clinical features of and genetic mutations in two cases of pseudohypoparathyroidism type Ⅰ a(PHP Ⅰ a) with early-onset skin nodules were analyzed.Both of the two patients were males,and their ages at onset were 2 and 3 months respectively.They both presented with early-onset skin nodules as the main clinical manifestation,and were clinically characterized by a round face,short neck and early obesity.Histopathological examination of skin lesions showed subcutaneous ectopic osteogenesis in both patients.The first patient had low blood calcium,high blood phosphorus,high parathyroid hormone (PTH),and gene sequencing showed a heterozygous mutation c.399delT causing a T base deletion at position 399 in exon 5 of the GNAS gene.The second patient had normal blood calcium and phosphorus levels as well as normal PTH levels at early stage,and gene sequencing showed a heterozygous mutation c.939delT causing a T base deletion at position 939 in exon 9 of the GNAS gene.The blood PTH level was found to increase in the second patient after 1-year follow-up.Both the patients were confirmedly diagnosed with PHP Ⅰa.After treatment with vitamin D3,no new skin nodules occurred,and the blood calcium and phosphorus levels returned to normal.

The causes of panniculitis are various and complex, and infection is one of the important causes. Streptococcal infection is the most common cause in Europe and the United States with a low incidence of tuberculosis. In areas with a high incidence of tuberculosis such as China, Mycobacterium tuberculosis infection is an important cause of panniculitis, which commonly manifests as erythema induratum of Bazin and erythema nodosum. Erythema induratum of Bazinis is most closely related to tuberculosis, often clinically manifests as nodules, plaques and ulcers on the flexor aspect of the lower extremities, and pathologically manifests as lobular panniculitis. Erythema nodosum can be considered as an early symptom of tuberculosis, and serves as a predictive indicator of tuberculosis. It often manifests as erythema, nodules and few ulcers on the extensor aspect of both lower limbs, and is pathologically characterized by septal panniculitis. Antituberculosis treatment often yields favorable outcomes in patients with erythema induratum of Bazin or erythema nodosum. Therefore, clarifying the relationship between Mycobacterium tuberculosis and panniculitis is of great significance to the treatment and prognosis of panniculitis, especially in areas with a high incidence of tuberculosis.

Amyloid deposits are one of the hallmark pathological lesions of Alzheimer's disease (AD). They can be visualized by thioflavin-S, silver impregnation, Congo red staining, and immunohistochemical reactions. However, that amyloid deposits generate blue autofluorescence (auto-F) has been ignored. Here, we report that visible light-induced auto-F of senile plaques (SPs) was detected and validated with conventional methods. Brain slices from APP/PS1 (amyloid precursor protein/presenilin 1) transgenic mice were mounted on slides, rinsed, coverslipped and observed for details of the imaging and spectral characteristics of the auto-F of SPs. Then the slices were treated with the above classic methods for comparative validation. We found that the SP auto-F was greatest under blue-violet excitation with a specific emission spectrum, and was much easier, more sensitive, and reliable than the classic methods. Because it does not damage slices, observation of auto-F can be combined with all post-staining techniques in slices and for brain-wide imaging in AD.

A male patient, who was aged 3 months and 12 days, presented with well-circumscribed erythema and scales on the scrotum, perineum, buttocks and perianal region at 1 month after birth. The lesions gradually involved the perioral and axillary regions, flexor aspect of the elbow, popliteal fossa and neck. Shortness of breath, crying, dysphoria and vomiting occurred without fever and cough 3 days before hospitalization. Laboratory examinations at admission showed metabolic acidosis, hyperlactacidemia, hyperammonemia and organic aciduria. Second-generation sequencing and Sanger sequencing of the holocarboxylase synthetase gene revealed a known mutation c.1522C>T in exon 9 and a novel mutation c.1796_1814del in exon 11. According to a guideline from the American College of Medical Genetics and Genomics, this novel mutation was ranked as a pathogenic mutation. The patient was diagnosed as multiple carboxylase deficiency. His clinical symptoms were improved after oral biotin treatment, no neurological symptoms or signs were observed.