ObjectiveTo observe the effect of Huayu Mingmu prescription on retinal angiogenesis and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）-hypoxia inducible factor-1α/vascular endothelial growth factor A （HIF-1α/VEGFA） signaling pathway in diabetic retinopathy （DR） rats. MethodsSixty-four SPF-grade male SD rats were used in the study. Eleven rats were randomly selected as the normal group， while the remaining 53 rats were fed a high-sugar， high-fat diet combined with low-dose streptozotocin （STZ） intraperitoneal injection to establish a type 2 diabetes mellitus （T2DM） rat model. DR model evaluation was performed after 12 weeks of diabetes. The rats were then divided into model， low-dose， medium-dose， and high-dose groups of Huayu Mingmu prescription （9.29， 18.57， 37.14 g·kg^-1）， and a calcium dobesilate group （0.16 g·kg^-1）， with 10 rats in each group. The rats were orally administered the corresponding doses of Huayu Mingmu prescription and calcium dobesilate. The normal and model groups received equal volumes of physiological saline via gavage for 8 consecutive weeks. Retinal vascular changes were observed through fundus photography， and pathological changes in retinal tissue were evaluated using hematoxylin-eosin （HE） staining. Retinal microvascular pathological changes were examined through retinal vascular network preparation and periodic acid-Schiff （PAS） staining. Immunofluorescence （IF） was used to detect the expression of VEGFA and angiopoietin-2 （Ang-2） in retinal tissue. Western blot was employed to detect the protein expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. ResultsCompared with the normal group， the model group exhibited significant pathological changes in retinal tissue， including the appearance of acellular capillaries， as well as significant endothelial cell （E） proliferation and pericyte （P） loss （P<0.01）. The E/P was significantly elevated （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly increased （P<0.01）， and the expression of Ang-2 protein was significantly elevated （P<0.01）. In contrast， retinal tissue in the treatment groups showed alleviated pathological changes， with reduced endothelial cell proliferation and pericyte loss （P<0.05， P<0.01）. Among the treatment groups， the high-dose Huayu Mingmu prescription and the calcium dobesilate group exhibited a decreased E/P （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly reduced （P<0.05， P<0.01）， and the expression of Ang-2 protein was significantly decreased （P<0.01）. ConclusionHuayu Mingmu prescription can intervene in retinal neovascularization in DR rats， delay the progression of DR， and its mechanism may be related to antagonizing the PI3K/Akt/mTOR-HIF-1α/VEGFA signaling pathway.

BackgroundThe depressive episode is one of the most prevalent mental illnesses worldwide. Relaxation therapy as a psychotherapy for depressive disorder has shown itself to be a viable tool， yet the existing research on relaxation therapy combined with sertraline in the treatment of depressive episodes in children and adolescents is severely limited. ObjectiveTo discuss the effect of relaxation therapy combined with sertraline on the new-onset depressive episodes in children and adolescents， and to provide references for the treatment of depressive episodes in children and adolescents. MethodsFrom January 1， 2019 to December 31， 2020， a sample of 422 children and adolescents with depressive episodes attending the Child Mental Health Department of Sichuan Mental Health Center and fulfilling the International Classification of Diseases， tenth edition （ICD-10） diagnostic criteria were enrolled， and they were classified into study group （n=208） and control group （n=214） using random number table method. All participants were offered sertraline， based on this， study group was assigned to relaxation therapy for 25~30 min per day， five days per week for a period of two weeks. Hamilton Depression Scale 24-item （HAMD-24） and Hamilton Anxiety Scale （HAMA） were applied at the enrollment， the end of 2 weeks of treatment and the end of the 2^nd week after discharge. ResultsA total of 369 patients completed the study， including 185 in study group and 184 in control group. Analysis on HAMD-24 scores revealed a significant time effect， group effect and time×group interaction effect （F=813.279， 17.625， 8 994.905， P<0.01）. Significant time effect， group effect， and time×group interaction effect were noted on HAMA scores （F=635.041， 10.716， 13 945.986， P<0.01）. A reduction in HAMD-24 and HAMA scores was reported in study group at end of 2 weeks of treatment and end of the 2^nd week after discharge compared with baseline （t=0.924， 0.359， P<0.01）. At the end of the 2^nd week after discharge， study group scored lower on HAMD-24 and HAMA compared to control group （t=0.210， 0.720， P<0.05）. At the end of 2 weeks of treatment， study group resulted in greater improvements in depressive symptoms and anxiety symptoms than those of control group （95.14% vs. 66.30%， 89.18% vs. 71.74%， χ²=78.942， 22.526， P<0.05）. The overall efficacy rate yielded no statistical difference between two groups at end of the 2^nd week after discharge （P>0.05）， and no statistical difference was found in the adverse reactions between the two groups （P>0.05）. ConclusionCompared with sertraline alone， its combination with relaxation therapy may achieve a better short-term efficacy in the treatment of depressive episode in children and adolescents. ［Funded by Sichuan Medical Scientific Research Project （number， S18020）］

Objective:To explore the stage connotation and characteristics of original research in the field of biomedicine.Methods:Through theoretical analysis and case studies, the original research in the field of biomedicine is subdivided into four subtypes, and the development laws and countermeasures are discussed in this paper.Results:The original research in biomedicine can be divided into four subtypes according to its dynamic process, which includes Budding (0-0.1), Bottleneck (0.1-1), Expansion (1-N) and Iteration (1- New 1). Each subtype has different technological advancement, maturity, scale, and influence.Conclusions:Analysing the original connotation and laws of the subtypes of 4 original research in biomedicine provides relevant suggestions on formulating funding, development strategies, as well as promoting original medical innovation.

To investigate the effectiveness and safety of ultrasound-guided microwave ablation (MWA) in treatment of primary hyperparathyroidism (PHPT). A total of 12 PHPT patients with parathyroid adenoma were treated with MWA in Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine from May 2019 to February 2021. The patients were followed up once every 3 months for 3-12 months. Levels of serum parathyroid hormone (PTH), calcium and phosphorus were detected before and 20 min, 4h and 1day after ablation, and during follow-up period. The volume and volume reduction rate of parathyroid lesion were compared before the treatment and at the end of follow-up. The technical and clinical success of MWA were assessed as well. At the end of follow-up, median serum PTH [66.60 (42.21,80.03) ng/L vs.169.90 (89.01,396.50) ng/L] and calcium [2.39 (2.32,2.49) mmol/L vs. 2.75 (2.57,2.96) mmol/L] levels in 12 patients decreased significantly (all P<0.05). A complete response in terms of PTH and calcium levels was achieved in 6 of the 12 patients, while 4 of the patients had slightly elevated PTH levels just above the upper limit of normal reference range, and 2 of the patients remained abnormal PTH and calcium levels. The clinical cure rate was 50%. The volumes of all lesion after ablation were significantly decreased ( P<0.05), with the technical success rate reaching 92.3%. No serious complications were observed. Ultrasound-guided MWA, thus, is safe and effective in the treatment of PHPT.

Objective:To investigate clinical significance and related factors of magnetic resonance hyperintense vessel sign (HVS).Methods:The clinical data and related imaging parameters of 109 patients with acute anterior circulation occlusion cerebral infarction, who admitted to Northern Theater Command General Hospital of People′s Liberation Army from April 2017 to August 2019, were analyzed retrospectively. Brain magnetic resonance imaging (MRI) examinations including fluid attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI) and three dimensional time of flight magnetic resonance angiography (3D TOF MRA) sequences within 24 hours of onset were performed. According to the distribution range of HVS in FLAIR sequence, the patients were divided into four grades (0, 1, 2 and 3), grades 0 and 1 belonging to HVS low grade group, and grades 2 and 3 HVS high grade group. Univariate and multivariate analyses were made to explore related factors of HVS. Fifty-two patients who completed baseline CT within six hours of onset before MRI examination were performed CT-Alberta Stroke Program Early CT Score (CT-ASPECTS) and DWI-Alberta Stroke Program Early CT Score (DWI-ASPECTS).The difference between CT-ASPECTS and DWI-ASPECTS was calculated. When the difference of ASPECTS ≤1, they were categorized as ASPECTS unchanged group (AN group); when the difference of ASPECTS>1, they were categorized as ASPECTS changed group (AY group). These two groups were compared to explore whether there was any difference in HVS grade, and Spearman correlation analysis was performed to investigate the relationship between HVS grade and the difference of ASPECTS.Results:The difference of hyperlipidemia, TOAST classification (large artery atherosclerosis (LAA), other etiology (SOE) or undetermined etiology (SUE)) and Willis circle classification (types Ⅰ, Ⅱ, Ⅲ and Ⅳ) between HVS groups were remarkable (58.6% (34/58) vs 37.3% (19/51), χ2=4.959, P=0.026; 23/5/23 vs 43/1/14, P=0.004; 3/14/12/22 vs 7/29/14/8, χ2=13.124, P=0.004). Other clinical factors and the locations of vessel occlusion did not show significant difference ( P>0.05). Multivariate Logistic regression analysis indicated that LAA in TOAST classification (LAA vs SOE or SUE, OR=3.054, 95% CI1.257-7.422, P=0.014), Willis circle type Ⅰ (type Ⅰ vs type Ⅳ, OR=5.494, 95% CI1.074-28.091, P=0.041), and type Ⅱ (type Ⅱ vs type Ⅳ, OR=5.571, 95% CI1.895-16.372, P=0.002) were independent related factors to stimulate wide distribution of HVS. The grades of HVS were significantly different between the AN group and the AY group (1/15 vs18/18, χ2=9.114, P=0.002). Spearman correlation analysis showed that HVS grade was negatively correlated with the difference of ASPECTS ( r=-0.573, P<0.001). Conclusions:Both TOAST and Willis circle classifications are crucial factors affecting HVS distribution. HVS distribution range reflects the status of collateral compensatory. Recognizing HVS may help to evaluate the progress of early cerebral infarction volume.

By analyzing the main problems existing in the current management of medical devices for clinical trials, this study proposes a feasible management model and specific requirements for acceptance, distribution, storage and recovery combining with the characteristics of medical consumable equipment and diagnostic reagent, which provides a favorable guarantee for the authenticity and reliability of clinical trials.
Clinical Trials as Topic ; Equipment and Supplies/standards* ; Indicators and Reagents/standards* ; Reproducibility of Results ; Research Design/standards*

Objective: To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method: Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results: All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.

Objective To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method Clinicopathological features and clinical follow?up (39-123 months and a median follow?up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin?and?eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet?ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow?up, had been disease?free during the follow?up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2?positivity was 1/7. The proliferation index Ki?67 ranged from less than 5% to 30%, and Ki?67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet?ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.

Objective To evaluate the relationship between spinal Sonic hedgehog (Shh) signaling pathway and inflammatory responses in rats with neuropathic pain (NP).Methods Forty-eight cleangrade healthy male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were divided into 4 groups (n=12 each) using a random number table method:sham operation group (group S),group NP,dimethyl sulfoxide (DMSO) group (group D) and specific Shh signaling pathway inhibitor cyclopamine group (group CP).Spared nerve injury was produced by exposing the sciatic nerve and branches followed by ligation and transection of tibial and common fibular nerves in anesthetized rats.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before establishing the model and 1 and 7 days after establishing the model.,The animals were sacrificed after measurement of pain threshold at 7 days after operation,and the lumbar segment L4-6 of the spinal cord was obtained for determination of the expression of Shh,Patched homolog (Ptch),Smoothened (Smo) and zinc finger-containing transcription factors 1 (Gli1) (by Western blot) and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) (by enzyme-linked immunosorbent assay).Results Compared with group S,the MWT was significantly decreased,the expression of Shh,Patched,Smo and Gli1 was up-regulated,and the contents of TNF-α and IL-1β were increased in NP,D and CP groups (P＜0.05).Compared with group NP,the MWT was significantly increased,the expression of Shh,Patched,Smo and Gli1 was down-regulated,and the contents of TNF-α and IL-1β were decreased in group CP (P＜0.05),and no significant change was found in the parameters mentioned above in group D (P＜0.05).Conclusion The mechanism by which Shh signaling pathway is involved in the development and mainterance of inflammatory responses is related to inhibiting inflammatory responses of the spinal cord in rats with NP.