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.

Objective To explore the clinical and epidemiological characteristics of fosfomycin(FOS)-resistant hy-pervirulent carbapenem-resistant Klebsiella pneumoniae(hv-CRKP)strains,as well as potential molecular mecha-nisms of FOS resistance,and provide reference for clinical anti-infection treatment decision making.Methods Through antimicrobial susceptibility testing,non-repetitive hv-CRKP strains from a tertiary first-class hospital from January to December 2023 were screened and collected.The clinical characteristics and antimicrobial resistance were analyzed,and the molecular epidemiological characteristics of FOS non-susceptible hv-CRKP was studied by whole genome sequencing.Results A total of 73 hv-CRKP strains were included in the analysis,out of which 34 strains(46.6％)were resistant to FOS.The incidence of diabetes mellitus in patients in the FOS non-susceptible group was higher than that in the FOS susceptible group(P＜0.05).There was no statistically significant difference among other clinical characteristics.Antimicrobial susceptibility results showed that,except for tigecycline,colistin,cefta-zidime/avibactam,and FOS,the resistance rates of hv-CRKP to other common antimicrobial agents were all＞90％.The detection of capsule serotypes and virulence genes showed that all hv-CRKP were Klebsiella pneumoniae car-bapenemase(KPC)-producing ST11 strains,with the main serotypes being KL64(47.9％)and KL25(52.1％).There was no statistically significant difference in distribution of hv-CRKP capsule serotype between the FOS sus-ceptible and FOS non-susceptible groups.Resistance gene detection results showed that the carbapenem-resistance gene blaKPC as well as FOS resistance genes fosA and fos A6 were widely presented in hv-CRKP,with only one strain carrying the fosA3 gene detected in the FOS non-susceptible group.All 73 hv-CRKP strains carried the Leu359Gln mutation modification in murA,and some had mutations in the transport system-related gene glpT.No other FOS modification enzyme resistance genes were detected,such as fosA2,fosA5,fosA10,fosB,fosC,and fosX.Conclusion hv-CRKP has a high resistance rate to FOS.Modification mutations in murA and glpT,as well as the wide presence of FOS resistance genes fosA and fosA6 are the main mechanisms of FOS resistance in this study.It should be noted that fosA gene may be captured by strong promoters-containing high copy plasmids,lead-ing to FOS resistance.

Objective To explore the clinical and epidemiological characteristics of fosfomycin(FOS)-resistant hy-pervirulent carbapenem-resistant Klebsiella pneumoniae(hv-CRKP)strains,as well as potential molecular mecha-nisms of FOS resistance,and provide reference for clinical anti-infection treatment decision making.Methods Through antimicrobial susceptibility testing,non-repetitive hv-CRKP strains from a tertiary first-class hospital from January to December 2023 were screened and collected.The clinical characteristics and antimicrobial resistance were analyzed,and the molecular epidemiological characteristics of FOS non-susceptible hv-CRKP was studied by whole genome sequencing.Results A total of 73 hv-CRKP strains were included in the analysis,out of which 34 strains(46.6％)were resistant to FOS.The incidence of diabetes mellitus in patients in the FOS non-susceptible group was higher than that in the FOS susceptible group(P＜0.05).There was no statistically significant difference among other clinical characteristics.Antimicrobial susceptibility results showed that,except for tigecycline,colistin,cefta-zidime/avibactam,and FOS,the resistance rates of hv-CRKP to other common antimicrobial agents were all＞90％.The detection of capsule serotypes and virulence genes showed that all hv-CRKP were Klebsiella pneumoniae car-bapenemase(KPC)-producing ST11 strains,with the main serotypes being KL64(47.9％)and KL25(52.1％).There was no statistically significant difference in distribution of hv-CRKP capsule serotype between the FOS sus-ceptible and FOS non-susceptible groups.Resistance gene detection results showed that the carbapenem-resistance gene blaKPC as well as FOS resistance genes fosA and fos A6 were widely presented in hv-CRKP,with only one strain carrying the fosA3 gene detected in the FOS non-susceptible group.All 73 hv-CRKP strains carried the Leu359Gln mutation modification in murA,and some had mutations in the transport system-related gene glpT.No other FOS modification enzyme resistance genes were detected,such as fosA2,fosA5,fosA10,fosB,fosC,and fosX.Conclusion hv-CRKP has a high resistance rate to FOS.Modification mutations in murA and glpT,as well as the wide presence of FOS resistance genes fosA and fosA6 are the main mechanisms of FOS resistance in this study.It should be noted that fosA gene may be captured by strong promoters-containing high copy plasmids,lead-ing to FOS resistance.

Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1⁺ SCs). Darbepoetin alpha (a long-acting EPO analog, EPO_anlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin^- Sca-1⁺ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPO_anlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin^- Sca-1⁺ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1⁺ SCs.
Animals ; Mice ; Ventricular Remodeling ; Erythropoietin ; Myocardial Infarction ; Heart ; Stem Cells

Objective: To investigate the diagnosis and treatment of Chiari malformation patients with hoarseness and other otorhinolaryngological symptoms. Methods: The clinical data of 18 patients of Chiari malformation with hoarseness were retrospectively collected, which was composed of 5 men and 13 women, aged 3-71 with median age of 52. All the patients were admitted to the Affiliated Hospital of Qingdao University from January 1989 to January 2020. All patients underwent brain MRI and laryngoscopy. The patient's symptoms and first diagnosis department, diagnosis time, total course of disease, hoarseness course, diagnosis and treatment, and postoperative recovery time were summarized. Follow-up time was 3-16 years, with median follow-up time of 6.5 years. Descriptive methods were used for analysis. Results: The first visit departments of 18 patients included neurology (9 cases), otorhinolaryngology head and neck surgery (5 cases), pediatrics (2 cases), orthopedics (1 case) and respiratory department (1 case). Except for the 7 cases in neurology department, the other 11 patients were not diagnosed in time. The disease duration of 18 patients with Chiari malformation ranged from 2 months to 5 years, and hoarseness was present from 20 days to 5 years. After diagnosis, 9 patients underwent posterior fossa decompression surgery, and 1 of them underwent syrinx drainage at the same time. The symptoms of 8 cases improved significantly after operation, with the improvement time from 1 to 30 days. In addition, 9 patients chose conservative treatment, among whom 8 had no improvement in symptoms and 6 progressed. Conclusions: Posterior fossa decompression is an effective treatment for Chiari malformation, and the prognosis is good. Timely diagnosis and treatment can improve the prognosis of patients.
Male ; Humans ; Female ; Child ; Hoarseness/etiology* ; Retrospective Studies ; Conservative Treatment ; Drainage ; Laryngoscopy

Today, there is greater awareness on the association between oral diseases and respiration diseases after the outbreak of COVID-19. However, confusion regarding the oral health management and medical risk prevention for patients with chronic airway diseases has been remained among dental clinicians. Therefore, the dental experts of the Fifth General Dentistry Special Committee, Chinese Stomatological Association, combined with the experts of respiratory and critical care medicine, undertook the formation of consensus on the oral health management of patients with chronic airway diseases in order to help dental clinicians to evaluate medical risks and make better treatment decision in clinical practice. In the present consensus report, the relationship of oral diseases and chronic airway diseases, the oral health management and the treatment recommendations of patients with chronic airway diseases are provided.
COVID-19 ; Consensus ; Humans ; Oral Health ; Oral Medicine

With the aging process of population in the society, the prevalence of cardiovascular diseases (CVD) in China is increasing continuously and the number of dental patients with CVD is increasing gradually too. Due to the lack of guidelines for dental patients with CVD in our country, how to implement standardized preoperative evaluation and perioperative risk prevention remains a problem to be solved for dentists at present. The present expert consensus was reached by combining the clinical experiences of the expert group of the Fifth General Dentistry Special Committee, Chinese Stomatological Association and respiratory and cardiology experts in diagnosis and treatment for CVD patients, and by systematically summarizing the relevant international guidelines and literature regarding the relationship between CVD and oral diseases and the diagnosis and treatment of dental patients with heart failure, hypertension and antithrombotic therapy. The consensus aims to provide, for the dental clinicians, the criteria on diagnosis and treatment of CVD in dental patients in China so as to reduce the risk and complications, and finally to improve the treatment levels of dental patients with CVD in China.
Cardiovascular Diseases/prevention & control* ; China/epidemiology* ; Consensus ; Dental Care ; Humans ; Oral Medicine

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Prospective Studies ; China ; Ischemia ; Aortic Aneurysm, Abdominal/surgery*

Objective:To explore the effect of placing drainage or not on rapid rehabilitation after total knee arthroplasty (TKA). Methods:From January, 2018 to September, 2020, 80 patients with knee osteoarthritis who underwent primary TKA in our hospital were analyzed retrospectively, and they were divided into groups A and B, with 40 cases in each group. Drainage was placed routinely in group A and not in group B. The postoperative serum inflammatory factors, postoperative pain score, postoperative complication rate, postoperative time out of bed, hospital stay, knee function score, range of motion of knee and World Health Organization Quality Of Life-abbreviated version score (WHOQOL-BREF) were compared between two groups. Results:There was no significant difference in the levels of C-reactive protein between two groups on the 1st to 3rd day after operation (t < 0.410, P > 0.05). There was no significant difference in Visual Analogue Score between two groups from 12 h to 48 h after operation (t < 0.300, P > 0.05). The incidences of postoperative complications were 5.0% in group A and 2.5% in group B, with no significant difference between two groups (χ² = 0.346, P > 0.05). The time of getting out of bed and hospital stay was significantly shorter in group B than in group A (t > 4.863, P < 0.001). The scores of knee joint function, range of motion of knee and WHOQOL-BREF significantly increased after operation in both groups (t > 6.099, P < 0.001), however, there was no significant difference between two groups (P > 0.05). Conclusion:Placement or non-placement of drainage after primary TKA does not affect postoperative complications, knee joint function and quality of life of patients with knee osteoarthritis, however, non-placement of drainage can promote postoperative recovery and discharge.

Objective To observe the skin ultrastructure change of electric shock death rats and to test the expression changes of hypoxia-inducible factor-2α （HIF-2α） and heart type-fatty acid-binding protein （H-FABP） of myocardial cells, in order to provide basis for forensic identification of electric shock death. Methods The electric shock model of rats was established. The 72 rats were randomly divided into control group, electric shock death group and postmortem electric shock group. Each group was divided into three subgroups, immediate （0 min）, 30 min and 60 min after death. The skin changes of rats were observed by HE staining, the changes of skin ultrastructure were observed by scanning electron microscopy, and the expression of HIF-2α and H-FABP in rats myocardium was tested by immunohistochemical staining. Results The skin in the electric shock death group and postmortem electric shock group had no significant difference through the naked eye or by HE staining. Under the scanning electron microscope, a large number of cellular debris, cells with unclear boundaries, withered cracks, circular or elliptical holes scattered on the cell surface and irregular edges were observed. A large number of spherical foreign body particles were observed. Compared with the control group, the expression of HIF-2α in all electric shock death subgroups increased, reaching the peak immediately after death. In the postmortem electric shock group, HIF-2α expression only increased immediately after death, but was lower than that of electric shock death group （P<0.05）. Compared with the control group, the expression of H-FABP in all subgroups of electric shock death group and postmortem electric shock group significantly decreased. The expression of H-FABP in all subgroups of electric shock death group was lower than that of the postmortem electric shock group （P<0.05）. Conclusion Electric shock can increase HIF-2α expression and decrease H-FABP expression in the myocardium, which may be of forensic significance for the determination of electric shock death and identification of antemortem and postmortem electric shock.
Animals ; Autopsy ; Basic Helix-Loop-Helix Transcription Factors/metabolism* ; Fatty Acid Binding Protein 3/metabolism* ; Myocardium/metabolism* ; Myocytes, Cardiac/metabolism* ; Rats ; Skin/ultrastructure*