Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

BACKGROUND: Recent studies have shown that sodium-glucose cotransporters-2 (SGLT2) inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction (HFpEF) patients, but the exact mechanism is unknown. Ferritinophagy is a special form of selective autophagy that participates in ferroptosis. In this study, we aimed to investigate whether ferritinophagy was activated during the occurrence of HFpEF, and whether canagliflozin (CANA) could inhibite ferritinophagy. METHODS: We reared Dahl salt-sensitive (DSS) rats on a high-salt diet to construct a hypertensive HFpEF model, and simultaneously administered CANA intervention. Then we detected indicators related to ferritinophagy. RESULTS: The expression of nuclear receptor coactivator 4 (NCOA4), as well as microtubule-associated proteins light chain 3 (LC3), Bcl-2 interacting protein 1 (Beclin-1) and p62, were upregulated in HFpEF rats, accompanied by the downregulation of ferritin heavy chain 1 (FTH1), upregulation of mitochondrial iron transporter sideroflexin1 (SFXN1) and increased reactive oxygen species (ROS) production. Above changes were diminished by CANA. CONCLUSION Ferritinophagy is activated in HFpEF rats and then inhibited by CANA, leading to HFpEF benefits. The inhibition of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF, and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Immunoinflammation mediates the development of hypertensive nephropathy,and aberrant activation of the complement system,an important component of the innate immune system,plays an important role in the development of hypertensive nephropathy.Complement inhibition is expected to be a potential strategy for the treatment of hypertensive nephropathy.In this article,we summarized and reviewed relevant studies on the complement system in the development of hypertensive nephropathy,and complement-targeted drug therapy,aiming to provide new ideas for clinicians on the clinical diagnosis and treatment of hypertensive nephropathy.

Aim To investigate the impact of G pro-tein-coupled estrogen receptor 1(GPER1),also known as GPR30 playing a significant role in the nerv-ous system,on neuronal damage and cognitive dysfunc-tion following epileptic seizures.Methods The pro-tein expression levels of GPER1 and the DNA damage marker γ-H2AX in epileptic rats were assessed using Western blot.The hippocampal neuronal damage and apoptosis in pilocarpine-induced epilepsy models were evaluated using Nissl and TUNEL staining techniques,compared with GPER1 knockdown(GPER1-KD)rats with wild-type(WT)controls.The behavioral activi-ties,including memory and spatial learning,were mo-nitored during the chronic phase of epilepsy using the IntelliCage system.Results Compared to the control group,GPER1 protein expression in the cerebral cortex and hippocampus significantly increased 24 hours post-epilepsy onset.In the GPER1-KD+EP group,hipp-ocampal neuronal damage was more severe,with a sig-nificant increase in apoptotic neurons compared to the WT+EP group.The IntelliCage data revealed that during free exploration,nose contact,position learn-ing,and reverse position learning stages in the GPER1-KD+EP group exhibited fewer visits and a higher error rate than in the WT+EP group.Conclu-sions Deficiency in GPER1 impairs memory and spa-tial learning abilities following epilepsy,potentially due to exacerbated neuronal injury,apoptosis,and inflam-mation.GPER1 represents a promising therapeutic tar-get for mitigating post-epileptic nerve damage and cog-nitive impairment.

Lung cancer has the highest incidence rate and death rate in China.At present,the treatment of lung cancer includes radiotherapy,chemotherapy,immunotherapy,targeted therapy,etc.But currently available treatment strategies still cannot cure it.The toxic side effects of radiotherapy and chemotherapy limit their effectiveness and application.Surgical resection or com-bined radiotherapy and chemotherapy are the preferred treatment methods,but the overall efficacy is low.Protein post-translation-al modification is a hot topic in the field of tumor research.A lot of research has been carried out in the diagnosis and treatment of breast cancer,lymphoma and other diseases,and good results have been achieved in clinical practice.There are already rele-vant literature indicating that abnormal protein post modification is associated with the occurrence and development of lung canc-er.Therefore,this article reviews the research on lung cancer and protein post-translational modifications in recent years,in or-der to provide reference for the diagnosis and treatment of lung cancer.

This study was aimed at investigating the infection status of orf virus(ORFV)and the genetic evolution characteristics of epidemic ORFV isolates from Anhui province.A total of 303 clinical samples collected from major meat sheep breeding cities in An-hui during 2021-2023 were subjected to ORFV detection with fluorescence quantitative PCR(qPCR).The full-length B2L and F1L genes of ORFV in the positive samples were amplified through conventional PCR and sequenced.Genetic evolution analysis of the B2L and F1L genes was conducted after sequencing.The qPCR results indicated a total ORFV positivity rate in the clinical samples of 48.8%(148/303).Multiple sequence comparisons indicated that the B2L genes of 56 sample isolates shared 96.7%-100.0%DNA and 97.4%-100.0%amino acid sequence identity.Moreover,the F2L genes of 56 sample isolates shared 95.1%-100.0%DNA and 95.0%-100.0%amino acid sequence identity.The genetic evolution tree constructed with the B2L gene DNA sequences indicated sample iso-lates and 21 reference strains located in subgroup 1,and 26 sheep-derived sample isolates and 17 reference strains located in sub-group 2.Among them,the goat-derived sample isolate FY-TYA was located in the same sub-branch as the human-derived reference strain Gansu,whereas the goat-derived sample isolate FY-XQC was located in the same sub-branch as the reference strains China Vaccine and OV-HLJ-04.The genetic evolution tree constructed with the F1L gene DNA sequences showed,the goat sample isolates FY-XQA and FY-XQC were located in the same sub-branch as the sheep-derived reference strain Xinjiang.ORFV infection was rela-tively widespread in the major meat sheep breeding areas of Anhui province,and the DNA and amino acid sequences of the B2L and F1L genes of current circulating ORFV isolates showed different degrees of genetic variation,among which F1L gene had a high de-gree of variation.Furthermore,some goat-derived sample isolates were closely related to human,vaccine,and sheep-derived refer-ence strains.These results may serve as a reference for the prevention and control of ORFV infection in Anhui province.

In the dynamic process of organizational development,organizations tend to exhibit a tendency towards organizational inertia by maintaining its original behavior patterns.It introduces organizational inertia theory into the medical management.Based on the concept of organizational inertia,the concept of organizational inertia in medical quality and safety management was proposed.From the perspective of connotation of organizational inertia in medical quality and safety management,its essence was the failure of medical institutions to implement or achieve continuous improvement in medical standardized behavior.From the perspective of denotation,it includes six categories:structural inertia,institutional inertia,resource inertia,technological inertia,employee inertia,and cultural inertia.In addition,it explored how to overcome organizational inertia in medical quality and safety management,which can provide new ideas for sustainably improvement research and practice in medical quality and safety management.

[Purpose]To analyze the epidemiology and disease burden of gastric cancer in China,Japan and Republic of Korea from 1990 to 2021 and to predict changing trends from 2022 to 2031.[Methods]Data were obtained from the Global Burden of Disease(GBD)database.Age-stan-dardized incidence rate(ASIR),age-standardized mortality rate(ASMR),crude incidence rate(CIR),crude mortality rate(CMR),and disability-adjusted life years(DALY)rate for China,Japan and Republic of Korea from 1990 to 2021 were analyzed.Joinpoint regression software was used to analyze trends and calculate annual percentage changes.The autoregressive integrated moving average(ARIMA)model was applied to predict incidence and mortality from 2022 to 2031.[Results]In 2021,China had 611 799 new gastric cancer cases and 445 013 deaths,with an ASIR of 29.05/105 and an ASMR of 21.51/105,both significantly higher than those in Japan and Republic of Korea.Among men in China,both the ASIR(44.48/105)and ASMR(32.61/105)were the highest among the three countries,exceeding those in Japan(38.77/105,20.26/105)and Re-public of Korea(38.98/105,20.50/105).Among women,China had the highest number of new cases,but its ASIR(15.23/105)was slightly lower than Republic of Korea's(15.57/105)and higher than Japan's(14.66/105).However,China's ASMR among women(12.02/105)remained significantly higher than Japan's(7.64/105)and Republic of Korea's(8.08/105).From 1990 to 2021,ASIR,ASMR and DALY rates for gastric cancer declined in all three countries,but the reduction in China was significantly smaller than that in Japan and Republic of Korea,with Republic of Korea showing the steepest declines across all indicators.ARIMA model predictions indicated significant differences in disease burden among the three countries from 2022 to 2031.ASIR is projected to continue declining in China and Republic of Korea,reaching 22.87/105 and 12.45/105,respectively by 2031,while in Japan it is predicted to rise to 26.55/105.ASMR is projected to decline in all three countries,reaching 13.71/105(China),10.44/105(Japan),and 9.08/105(Republic of Korea)in 2031.[Conclusion]Among China,Japan and Republic of Korea,China had the highest ASIR and ASMR of gastric cancer in 2021.Moreover,from 1990 to 2021,the reductions in ASIR,ASMR and DALY rates for gastric cancer were the smallest in China compared to Japan and Republic of Korea.These findings suggest that the disease burden of gastric cancer remains substantial in China,high-lighting the need for increased efforts in gastric cancer screening and early diagnosis and treatment.

Objective To develop an innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis,and conduct clinical validation.Methods The design concept,technical principles and system composition of the innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis were introduced.A total of 73 patients(146 axillae)with axillary osmidrosis were enrolled as subjects,and underwent surgery using the newly developed surgical system.Clinical validation of the system was performed by evaluating postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Results The study demonstrated favorable clinical outcomes in the following aspects:postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Conclusion The minimally invasive rotary-cutting surgical system for axillary osmidrosis is rationally designed.The rotary-cutting puncture device is safe,effective,minimally invasive,and convenient for axillary osmidrosis surgery,warranting further clinical validation and widespread application.