Objective·To explore the relationship between abdominal fat area and the first-phase insulin secretion function of pancreatic β-cells in patients with type 2 diabetes,and to establish predictive models of nomogram.Methods·From October 2020 to February 2024,a total of 120 patients with type 2 diabetes,who were hospitalized in the Department of Endocrinology,Zhongshan Hospital,Fudan University,and underwent the arginine stimulation test,were recruited for the study.Patients were categorized into an insulin secretion function-preserved group(i.e.preserved group)and a depleted group according to the results of the arginine stimulation test.General information and laboratory parameters were collected.Subcutaneous fat area(SFA)and visceral fat area(VFA)were non-invasively measured by abdominal fat detector.The variables were screened by univariate analysis,and multivariate Logistic regression was used to identify the influencing factors,followed by the establishment of predictive models of nomogram.The area under the receiver operating characteristic curve(ROC curve)and concordance index(C-index)were used to evaluate the predictive performance of the models.Results·Seventy-four patients(61.7%)were assigned to the preserved group,and 46 patients(38.3%)to the depleted group.Patients in the depleted group had a longer diabetes duration,lower waist circumference,hip circumference,body mass index(BMI),uric acid,free triiodothyronine(FT3),adipose tissue insulin resistance(Adipo-IR),ankle brachial index(ABI),SFA and VFA,and higher brachial ankle pulse wave velocity(baPWV).Multivariate Logistic regression showed that SFA,VFA,FT3,baPWV,and ABI were independent risk factors for the depleted insulin secretion function.Nomogram models were constructed based on the above risk factors.Among them,the model comprising VFA,FT3,ABI,and baPWV showed the best predictive performance with a C-index of 0.81.Conclusion·SFA and VFA are lower in patients with depleted first-phase insulin secretion function of pancreatic β-cells.The nomogram model,including SFA or VFA,can be used to predict first-phase insulin secretion function of pancreatic β-cells in patients with type 2 diabetes.

Objective·To explore the relationship between abdominal fat area and the first-phase insulin secretion function of pancreatic β-cells in patients with type 2 diabetes,and to establish predictive models of nomogram.Methods·From October 2020 to February 2024,a total of 120 patients with type 2 diabetes,who were hospitalized in the Department of Endocrinology,Zhongshan Hospital,Fudan University,and underwent the arginine stimulation test,were recruited for the study.Patients were categorized into an insulin secretion function-preserved group(i.e.preserved group)and a depleted group according to the results of the arginine stimulation test.General information and laboratory parameters were collected.Subcutaneous fat area(SFA)and visceral fat area(VFA)were non-invasively measured by abdominal fat detector.The variables were screened by univariate analysis,and multivariate Logistic regression was used to identify the influencing factors,followed by the establishment of predictive models of nomogram.The area under the receiver operating characteristic curve(ROC curve)and concordance index(C-index)were used to evaluate the predictive performance of the models.Results·Seventy-four patients(61.7%)were assigned to the preserved group,and 46 patients(38.3%)to the depleted group.Patients in the depleted group had a longer diabetes duration,lower waist circumference,hip circumference,body mass index(BMI),uric acid,free triiodothyronine(FT3),adipose tissue insulin resistance(Adipo-IR),ankle brachial index(ABI),SFA and VFA,and higher brachial ankle pulse wave velocity(baPWV).Multivariate Logistic regression showed that SFA,VFA,FT3,baPWV,and ABI were independent risk factors for the depleted insulin secretion function.Nomogram models were constructed based on the above risk factors.Among them,the model comprising VFA,FT3,ABI,and baPWV showed the best predictive performance with a C-index of 0.81.Conclusion·SFA and VFA are lower in patients with depleted first-phase insulin secretion function of pancreatic β-cells.The nomogram model,including SFA or VFA,can be used to predict first-phase insulin secretion function of pancreatic β-cells in patients with type 2 diabetes.

Objective To explore the effect of atractylodes macrocephala lactone Ⅲ(AML Ⅲ)on nerve injury of rats with cerebral infarction.Methods The rats were randomly divided into sham operation group,model group(modified Longa thrombus method to prepare rat cerebral infarction model),low and high dose of AML Ⅲ group(AML Ⅲ-L,AML Ⅲ-H)and high dose AML Ⅲ+EX527(SIRT1 inhibitor)group(AMLⅢ-H-EX527).Neuro-logical function was assessed by Zea-Longa score.Serum tumor necrosis factor(TNF-α)and interleukin(IL-6,IL-1β)were measured by ELISA;The level of super oxide dismutase activity(SOD),malonaldehyde content(MDA),and catalase activity(CAT)in brain tissue was detected by commercially available kit;pathological changes of hippocampus tissue and the area of cerebral infarction were observed by HE staining and TTC staining microscopy respectively.Apoptosis of brain cells was identified by TUNEL staining;protein expression of Bax,Bcl-2,SIRT1,and Nrf2 in rat brain tissue was detected by Western blot assay.Results After the intervention by AML Ⅲ,the pathological injury of hippocampus neurons in rats was alleviated.The neurological function score,serum TNF-α,IL-6 and IL-1 β levels,apoptosis rate,cerebral infarction size,MDA level and Bax protein expression were all decreased.SOD and CAT activity,SIRT1,Nrf2,Bcl-2 and protein expression were all in-creased(P＜0.05);EX527 was able to alleviate the protective effect of AML Ⅲ on neural function damage in rats with cerebral infarction.Conclusions Atractylodes macrocephala lactone Ⅲ reduces the nerve function injury in rat models with cerebral infarction.

Objective:To investigate the effect of capsaicin on lipopolysaccharide(LPS)-induced microglial inflammatory response by modulating silent mating type information regulation 2 homolog 1(SIRT1)/high mobility group box-1 protein(HMGB1)/nuclear factor κB(NF-κB)signaling pathway.Methods:BV2 mouse microglia were cultured in vitro,and pretreated with capsaicin(10 μmol/L),SIRT1 inhibitor EX527(100 μmol/L),capsaicin+EX527(10 μmol/L capsaicin+100 μmol/L EX527)for 3 hours,and then treated with LPS(1 μg/ml)for 24 hours,the corresponding groups were LPS group,LPS+capsaicin group,LPS+EX527 group,and LPS+capsaicin+EX527 group,a normal cultured control group(Control)was also set up.Morphological changes of BV2 cells in each group were observed under a microscope;CCK-8 method was used to detect the viability of BV2 cells in each group;immunofluo-rescence staining was applied to detect the positive expressions of ionic calcium adaptor protein(Iba-1)and the polarization of M1(positive for CD16/32)/M2(positive for CD206)subtypes in BV2 cells in each group;ELISA was applied to detect levels of inflamma-tory factors in BV2 cells in each group;Western blot and co-immunoprecipitation were applied to detect expression of SIRT1/HMGB1/NF-κB signaling pathway-related proteins in each group.Results:Compared with Control group,BV2 cells in LPS group were atro-phied,with shortened processes,the cell viability,and levels of IL-1β,TNF-α and IL-6 were increased,Iba-1 positive expression of BV2 cells and M1 type BV2 cells were increased,while expression of SIRT1 protein was decreased,expressions of acetylated(ace)-HMGB1 protein,cytoplasmic HMGB1 protein and nuclear NF-κB protein were increased(P<0.05);after capsaicin pretreatment,the above conditions were improved,and the M2 type BV2 cells were increased;adding EX527 pretreatment on the basis of capsaicin pre-treatment,the above conditions were all aggravated.Conclusion:Capsaicin can inhibit the inflammatory response induced by LPS-in-duced BV2 cell activation,which may be achieved by modulating the SIRT1/HMGB1/NF-κB signaling pathway.

Hyaluronic acid (HA) injections have already been one of most popular cosmetic procedures for around 18 years. However, blindness is one of the most serious complications caused by HA injections. There is still no consensus on the treatment for vision recovery. The efficacy and safety of different delivery administration of hyaluronidase such as retrobulbar injection and endovascular intervention are still controversial so far. Based on current status, prevention is prior to treatment, which is widely recognized in the world. The pathogenic mechanism of blindness induced by filler injection is still not clear, and there exist several theories including the artery embolism, ischaemia, artery spasm and venous involvement, which are all related to the ophthalmic artery and its branches. Therefore, acquiring anatomic knowledge and the relevant parameters will help us prevent to damage the ophthalmic artery and its branches during HA injections. The mechanism, treatment progress and prognosis of blindness caused by HA injections in recent years were analyzed and summarized in this article. We hope it will help the clinician to improve the relevant knowledge about vision loss caused by HA injection, as well as to promote the safety of filler injection.

Hyaluronic acid (HA) injections have already been one of most popular cosmetic procedures for around 18 years. However, blindness is one of the most serious complications caused by HA injections. There is still no consensus on the treatment for vision recovery. The efficacy and safety of different delivery administration of hyaluronidase such as retrobulbar injection and endovascular intervention are still controversial so far. Based on current status, prevention is prior to treatment, which is widely recognized in the world. The pathogenic mechanism of blindness induced by filler injection is still not clear, and there exist several theories including the artery embolism, ischaemia, artery spasm and venous involvement, which are all related to the ophthalmic artery and its branches. Therefore, acquiring anatomic knowledge and the relevant parameters will help us prevent to damage the ophthalmic artery and its branches during HA injections. The mechanism, treatment progress and prognosis of blindness caused by HA injections in recent years were analyzed and summarized in this article. We hope it will help the clinician to improve the relevant knowledge about vision loss caused by HA injection, as well as to promote the safety of filler injection.

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Genetic composition plays critical roles in the pathogenesis of autism spectrum disorder (ASD). Especially, inherited and de novo intronic variants are often seen in patients with ASD. However, the biological significance of intronic variants is difficult to address. Here, among a Chinese ASD cohort, we identified a recurrent inherited intronic variant in the CHD7 gene, which is specifically enriched in East Asian populations. CHD7 has been implicated in numerous developmental disorders including CHARGE syndrome and ASD. To investigate whether the ASD-associated CHD7 intronic variant affects neural development, we established human embryonic stem cells carrying this variant using CRISPR/Cas9 methods and found that the level of CHD7 mRNA significantly decreased compared to control. Upon differentiation towards the forebrain neuronal lineage, we found that neural cells carrying the CHD7 intronic variant exhibited developmental delay and maturity defects. Importantly, we found that TBR1, a gene also implicated in ASD, was significantly increased in neurons carrying the CHD7 intronic variant, suggesting the intrinsic relevance among ASD genes. Furthermore, the morphological defects found in neurons carrying CHD7 intronic mutations were rescued by knocking down TBR1, indicating that TBR1 may be responsible for the defects in CHD7-related disorders. Finally, the CHD7 intronic variant generated three abnormal forms of transcripts through alternative splicing, which all exhibited loss-of-function in functional assays. Our study provides crucial evidence supporting the notion that the intronic variant of CHD7 is potentially an autism susceptibility site, shedding new light on identifying the functions of intronic variants in genetic studies of autism.

Objective:To figure out the structure and relevant data measurements of zygomatic ligament by cadaver anatomy and review of previous studies.Methods:From July 2018 to January 2020, the zygomatic areas of 20 Chinese frozen fresh cadaver hemifaces were dissected in the Department of Anatomy, Health Science Center of Hangzhou Normal University. Then the structures of zygomatic ligaments were shown. The characters of the ligament and the relationship with adjacent tissue were described and measured. And 16 previous studies were reviewed to get a comprehensive description about the characters of zygomatic ligaments.Results:Zygomatic ligaments were even and dense fibrous tissue structures distributed vertically between the skin and the subcutaneous tissue. Under the SMAS plane, the ligaments divided into two bundles. The origin of major bundle located beyond the origin of the zygomatic major muscle on the periosteum, and the origin of minor bundle located between the origin of the zygomatic minor and major muscle.Conclusions:The anatomy of the zygomatic ligament has a regular pattern, and its anatomical data has certain directive significance for clinical application.

Objective:To analyze the epidemiological and clinical characteristics of hospitalized patients with dengue fever in Guangdong Province in 2019, so as to provide reference for clinical diagnosis and treatment of dengue fever.Methods:The general data, laboratory examination data, clinical manifestations and prognosis data of 480 inpatients with dengue fever admitted to Eight People′s Hospital Affiliated to Guangzhou Medical University between January 4 and October 31, 2019 were analyzed retrospectively. The clinical and onset characteristics of patients with dengue fever were described.Results:Among 480 dengue patients, 442(92.1%) were dengue fever, 38(7.9%) were severe dengue, and 136(28.3%) had underlying diseases. The peak age of onset was mainly in young adults aged 20 to 49 years old, accounting for 66.0%(317/480) in total. The seasonal peak was mainly in August to October. There were 399(83.1%) local cases and 61(12.7%) imported cases. The most common clinical manifestations were fever (98.1%, 471/480), chills (72.9%, 350/480), headache (58.5%, 281/480) and bone/joint/muscle pain (67.1%, 322/480), followed by digestive tract symptoms and respiratory tract symptoms. Among 446 serum samples, 358 (80.3%) were dengue virus (DENV)-1, 54 (12.1%) were DENV-2, 34 (7.6%) were DENV-3. The main laboratory tests of the patients were leucopenia (65.8%, 316/480), low hematocrit (30.2%, 145/480), thrombocytopenia (48.3%, 232/480), neutropenia (44.8%, 215/480), elevated alanine aminotransferase (ALT) (37.7%, 181/480) and aspartate aminotransferase (AST) (59.4%, 285/480). Treatment mainly adopted symptomatic support treatment and active prevention of complications. The length of stay was (5.8±3.1) days (range 1.0-38.0 days). A total of 461(96.0%) patients were cured or improved.Conclusions:In 2019, the majority of dengue fever patients in Guangdong Province are young adults aged 20 to 49 years old, and the proportion of severe patients is high, with DENV-1 infection as the main type. After symptomatic support treatment and active prevention of complications, most of the dengue fever patients have a good prognosis.