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.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To investigate and elucidate the effect of trigonelline(TRG)on the ARPE-19 ferroptosis sig-naling pathway under hypoxia conditions.Methods ARPE-19 cells were routinely cultured and intervened with different concentrations of TRG.According to the optimal concentration(40 mg·L-1)of TRG determined for ARPE-19 interven-tion,the cells were divided into an NC group(routinely cultured for 24 h),a CoCl2 group(treated with 150 mmol·L-1 CoCl2 for 24 h),a Fer-1 group(treated at first with 1 μmol·L-1 Fer-1 for 12 h and then with 150 mumol·L-1 CoCl2 for 12 h),and a TRG group(treated at first with 40 mg·L-1 TRG for 24 h and then with 150 mmol·L-1 CoCl2 for 24 h).The levels of glutathione(GSH),malondialdehyde(MDA)and Fe2+ions in each group of cells were evaluated by detectionkits.The levels of reactive oxygen species(ROS)in each group of cells were detected by flow cytometry.Western blot was used to analyze the expression levels of hypoxia-induced factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family member 4(ACSL4)in each group of cells.The expression levels of VEGF and ACSL4 proteins in each group of cells were measured by immunofluorescence staining.Results The ROS levels in TRG and Fer-1 groups were significantly lower than those in the CoCl2 group(t=27.91,31.61;both P＜0.01).The change trend of MDA and Fe2+levels was the same with that of ROS levels in each group.Com-pared with those in the CoCl2 group,the GSH levels were increased significantly(t=15.95,12.76;both P＜0.01)and the relative expression levels of HIF-1α and VEGF proteins were decreased significantly in Fer-1 and TRG groups(all P＜0.01).The CoCl2 group had higher ACSL4 levels and lower GPX4 levels than the NC group(t=31.05,13.18;both P＜0.01).Fer-1 and TRG groups had lower ACSL4 expression levels and higher GPX4 expression levels than the CoCl2 group(all P＜0.01).The results of immunofluorescence staining showed that the expression levels of VEGF and ACSL4 proteins in the CoCl2 group were higher than those in the NC group.The expression levels of VEGF and ACSL4 proteins in Fer-1 and TRG groups were lower than those in the CoCl2 group.Conclusion TRG protects ARPE-19 cells from hypoxia-induced oxidative stress damage by inhibiting ferroptosis.

Objective:To explore the effect of repetitive transcranial magnetic stimulation (rTMS) on the cognition and ability in the activities of daily living (ADL) of persons with cerebral small vessel disease.Methods:A total of 71 patients with cognitive impairment due to cerebral small vessel disease were randomly divided into a control group ( n=35) and a treatment group ( n=36). The treatment group was further divided into a group with mild cognitive impairment (a score of 21 to 26 on the mini-mental state exam, n=23) and a moderate cognitive impairment group (scoring 10 to 20, n=13). The treatment groups received 10Hz rTMS, while the control group received sham rTMS. Before and after 90 days of treatment, all were assessed using the mini-mental state examination (MMSE) and the cognitive subscale of the vascular dementia assessment scale (VaDAS-cog). Ability in the activities of daily living was quantified using the Barthel Index (BI). Results:After treatment, significantly increased MMSE and BI scores, but significantly decreased VaDAS-cog scores were observed in both groups. At that point the treatment group showed a significantly higher average post-treatment MMSE score (25.61±2.94) and BI score (80.00±7.85), but a significantly lower average VaDAS-cog score (44.06±3.41) than the control group. The average MMSE scores were not significantly different between the mild and moderate cognitive impairment subgroups. No severe adverse reactions were observed during the rTMS treatment.Conclusions:The 10Hz rTMS can effectively improve the cognition and daily living ability of persons with cerebral small vessel disease.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective To investigae microbial community structure of lower respiratory tract in severe hospital-acquired pneumonia(SHAP)patients in intensive care unit(ICU)using metagenomic next-generation sequencing(mNGS).Methods mNGS was performed on bronchoalveolar lavage fluid(BALF)of 84 patients with SHAP.Patients were grouped based on age,smoking status,underlying diseases and duration of artificial airway.The differences in α diversity,β diversity,microbial composition and community structure of airway microbiota were compared between different groups.The differential airway microbiota associated with artificial airway were screened,and microbial co-occurrence networks was constructed to observe the interaction in microorganisms.Results Results of α diversity analysis revealed that diversity and evenness of the microbial community were higher in young adults compared to those of middle-aged patients,while microbial diversity and evenness were significantly reduced in patients with comorbid stroke.In the group of artificial airway treatment,the diversity and uniformity of microorganisms decreased as the duration of artificial airway treatment increased.The diversity was the lowest when the artificial airway treatment lasted for more than 3 days.β diversity analysis confirmed that there were significant differences in the distinct microbial community structures between the>3 days support group and the non-intubated and≤3 days support cohorts.Acinetobacter baumannii was dominant in all groups.The bacterial diversity was significantly higher in the middle-aged group,the non-smoking group,the group without artificial airway therapy,the group without diabetes mellitus,the group with artificial airway therapy≥3 days and the group with chronic lung disease than those of other groups.In particular,pseudomonas aeruginosa,corynebacterium striatum and veillonella parvula were enriched in these groups.Difference analysis showed that there were significant differences in pseudomonas aeruginosa and corynebacterium striatum between the group with artificial airway treatment>3 days,the group without artificial airway therapy and the group with artificial airway treatment≤3 days.Network co-occurrence showed that there may be synergistic or antagonistic relationships between some microorganisms.Conclusion The microbial diversity of the lower respiratory tract in patients with SHAP significantly decreases in the elderly,those with concurrent stroke and those receiving artificial airway treatment.For these groups,rational use of antibiotics should be adopted to guide precise anti-infection treatment.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Whole-genome sequencing, serotype typing, MLST typing, population genetic structure analysis, and core-genome single nucleotide polymorphism (cgSNP) analysis were performed on 23 strains of mucoid Haemophilus influenzae collected from the Laboratory Center of Hunan Children′s Hospital from January 2021 to December 2022. Drug susceptibility tests were conducted using the automated microbial identification and susceptibility analysis system AF-600, and virulence genes and drug resistance genes were analyzed based on the whole-genome sequences. Based on the serotype typing of whole-genome sequencing, all 23 strains were Haemophilus influenzae type b (Hib). MLST analysis revealed that the 23 strains belonged to six ST types, among which 10 strains (43.5%) were ST386, 5 strains (21.7%) were ST18, and 2 strains (8.7%) were the newly discovered ST2887. Bayesian population structure analysis (BAPS) showed three distinct populations. The results of the virulence gene analysis showed that the carriage rates of genes encoding capsule-related proteins and those associated with bacterial immune regulation and inflammatory signaling pathways were all 100%. However, the ompP5 gene related to bacterial adhesion, and the hgpC and hxuA genes related to bacterial protein metabolism were all present in the newly discovered ST2887. The in vitro drug susceptibility test results of 23 strains of mucoid Hib showed that the resistance rates to ampicillin, cefuroxime, and Trimethoprim-sulfamethoxazole were 13.0%(3 strains), 13.0%(3 strains), and 87.0%(20 strains), respectively. They were sensitive to other beta-lactam drugs. All the 23 strains of mucoid Haemophilus influenzae infected children were Hib, and the main ST types were ST386 and ST18. It is very important to advocate Hib vaccination.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.