Objective:To investigate the clinical and genetic characteristics of a Henan Han family with pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), aiming to enhance understanding of this disease.Methods:The proband was first admitted to the Department of Neurology, Henan Provincial People′s Hospital, Fuwai Central China Cardiovascular Hospital in December 2019 due to cerebral infarction and unilateral limb numbness and weakness. Detailed medical history collection, pedigree mapping, whole-exome sequencing screening, and Sanger sequencing validation were performed for the proband and family members. The patients′ clinical manifestations, imaging features, neuropsychological scale assessment results, and pathological changes were summarized, and genetic analysis was conducted on the gene variant site. Relevant literature was reviewed to summarize the characteristics of PADMAL.Results:The proband was a 47-year-old female, with 3 generations of family members affected, including 7 patients, 3 of whom had died. The clinical features of the patients were similar, with the first stroke occurring around the age of 40, without vascular risk factors such as hypertension or diabetes. The main clinical manifestation was unilateral limb numbness and weakness. The proband and her niece sought medical attention due to stroke symptoms. Brain magnetic resonance imaging revealed acute infarct lesions located in the pons, accompanied by multiple oval infarct foci (the "raisin bread sign") and white matter hyperintensity changes. Genetic testing showed that 4 patients carried a heterozygous c. *34GT mutation in the 3′-untranslated region (3′-UTR) of the COL4A1 gene, while the other 4 unaffected family members did not carry this variant, consistent with genotype- phenotype co-segregation in the family. Conclusions:PADMAL is an extremely rare monogenic cerebral small vessel disease caused by pathogenic variants in the 3′-UTR of the COL4A1 gene. The "raisin bread sign" in the pons is a relatively specific imaging feature that distinguishes it from other cerebral small vessel diseases. For patients with this sign, genetic testing for PADMAL should be considered.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective:To investigate the clinical and genetic characteristics of a Henan Han family with pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), aiming to enhance understanding of this disease.Methods:The proband was first admitted to the Department of Neurology, Henan Provincial People′s Hospital, Fuwai Central China Cardiovascular Hospital in December 2019 due to cerebral infarction and unilateral limb numbness and weakness. Detailed medical history collection, pedigree mapping, whole-exome sequencing screening, and Sanger sequencing validation were performed for the proband and family members. The patients′ clinical manifestations, imaging features, neuropsychological scale assessment results, and pathological changes were summarized, and genetic analysis was conducted on the gene variant site. Relevant literature was reviewed to summarize the characteristics of PADMAL.Results:The proband was a 47-year-old female, with 3 generations of family members affected, including 7 patients, 3 of whom had died. The clinical features of the patients were similar, with the first stroke occurring around the age of 40, without vascular risk factors such as hypertension or diabetes. The main clinical manifestation was unilateral limb numbness and weakness. The proband and her niece sought medical attention due to stroke symptoms. Brain magnetic resonance imaging revealed acute infarct lesions located in the pons, accompanied by multiple oval infarct foci (the "raisin bread sign") and white matter hyperintensity changes. Genetic testing showed that 4 patients carried a heterozygous c. *34GT mutation in the 3′-untranslated region (3′-UTR) of the COL4A1 gene, while the other 4 unaffected family members did not carry this variant, consistent with genotype- phenotype co-segregation in the family. Conclusions:PADMAL is an extremely rare monogenic cerebral small vessel disease caused by pathogenic variants in the 3′-UTR of the COL4A1 gene. The "raisin bread sign" in the pons is a relatively specific imaging feature that distinguishes it from other cerebral small vessel diseases. For patients with this sign, genetic testing for PADMAL should be considered.

Objective:This article introduces a novel technique for totally laparoscopic, right thoracic approach, esophagojejunostomy for digestive tract reconstruction.Methods:A retrospective analysis was conducted on the clinical data of patients with adenocarcinoma of the esophagogastric junction who successfully underwent totally laparoscopic esophagojejunostomy via the right thoracic approach at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between February 2022 and March 2022.The surgical procedure was performed as follows:(1)Following total laparoscopic resection of the gastric tumor and lymph node dissection, the specimen was transected distal to the tumor margin. The specimen was then placed into a retrieval bag and extracted through the umbilical observation port.(2)Dissection was continued through the esophageal hiatus to mobilize the esophagus. The tumor-bearing tissue, along with the esophagus, was delivered into the thoracic cavity via the esophageal hiatus.(3)The jejunum was transected 20 cm distal to the ligament of Treitz. The distal Jejunum was mobilized for 15-20 cm and subsequently delivered into the thoracic cavity through the esophageal hiatus.(4)A Roux-en-Y jejunojejunostomy was constructed 45-50 cm distal to the cut end of the distal jejunal limb; the mesenteric defect was closed, and the duodenal stump was reinforced.(5)The patient was repositioned into the left lateral decubitus position. Port placement was established as follows: the observation port at the 7th intercostal space (ICS) in the right midaxillary line, the main operating port at the 4th ICS in the anterior axillary line, and the assistant operating port at the 9th ICS in the scapular line.(6)The main operating port incision was enlarged. Using a purse-string instrument, the esophagus was clamped and transected at least 5 cm proximal to the upper tumor margin, and the specimen was removed. (7)The distal jejunum was delivered into the thoracic cavity via the esophageal hiatus. Under total laparoscopic visualization, esophagojejunostomy was completed.Results:Both patients who underwent totally laparoscopic esophagojejunostomy via the right thoracic cavity successfully completed the procedure without conversion to laparotomy, unplanned reoperation, or any intraoperative/postoperative complications. The patients recovered well postoperatively, with no evidence of abdominal or thoracic hemorrhage. Postoperative computed tomography (CT) scans of the chest and abdomen confirmed the absence of anastomotic leakage or other related complications.Conclusions:The esophagojejunostomy was performed totally laparoscopically via the right thoracic cavity. This approach overcomes the drawback of significant trauma associated with open surgery while ensuring safe esophageal resection margins and thorough lymph node dissection. This technique offers advantages including minimal invasiveness, accelerated postoperative recovery, and a reduced incidence of reflux esophagitis. To our knowledge, no similar method of digestive tract reconstruction has been reported in the literature. Its novelty and clinical potential may offer new therapeutic options for patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG).

Objective:This article introduces a novel technique for totally laparoscopic, right thoracic approach, esophagojejunostomy for digestive tract reconstruction.Methods:A retrospective analysis was conducted on the clinical data of patients with adenocarcinoma of the esophagogastric junction who successfully underwent totally laparoscopic esophagojejunostomy via the right thoracic approach at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between February 2022 and March 2022.The surgical procedure was performed as follows:(1)Following total laparoscopic resection of the gastric tumor and lymph node dissection, the specimen was transected distal to the tumor margin. The specimen was then placed into a retrieval bag and extracted through the umbilical observation port.(2)Dissection was continued through the esophageal hiatus to mobilize the esophagus. The tumor-bearing tissue, along with the esophagus, was delivered into the thoracic cavity via the esophageal hiatus.(3)The jejunum was transected 20 cm distal to the ligament of Treitz. The distal Jejunum was mobilized for 15-20 cm and subsequently delivered into the thoracic cavity through the esophageal hiatus.(4)A Roux-en-Y jejunojejunostomy was constructed 45-50 cm distal to the cut end of the distal jejunal limb; the mesenteric defect was closed, and the duodenal stump was reinforced.(5)The patient was repositioned into the left lateral decubitus position. Port placement was established as follows: the observation port at the 7th intercostal space (ICS) in the right midaxillary line, the main operating port at the 4th ICS in the anterior axillary line, and the assistant operating port at the 9th ICS in the scapular line.(6)The main operating port incision was enlarged. Using a purse-string instrument, the esophagus was clamped and transected at least 5 cm proximal to the upper tumor margin, and the specimen was removed. (7)The distal jejunum was delivered into the thoracic cavity via the esophageal hiatus. Under total laparoscopic visualization, esophagojejunostomy was completed.Results:Both patients who underwent totally laparoscopic esophagojejunostomy via the right thoracic cavity successfully completed the procedure without conversion to laparotomy, unplanned reoperation, or any intraoperative/postoperative complications. The patients recovered well postoperatively, with no evidence of abdominal or thoracic hemorrhage. Postoperative computed tomography (CT) scans of the chest and abdomen confirmed the absence of anastomotic leakage or other related complications.Conclusions:The esophagojejunostomy was performed totally laparoscopically via the right thoracic cavity. This approach overcomes the drawback of significant trauma associated with open surgery while ensuring safe esophageal resection margins and thorough lymph node dissection. This technique offers advantages including minimal invasiveness, accelerated postoperative recovery, and a reduced incidence of reflux esophagitis. To our knowledge, no similar method of digestive tract reconstruction has been reported in the literature. Its novelty and clinical potential may offer new therapeutic options for patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG).

Objective This study aims to assess the role of DNA methylation changes in tongue cancer through a comprehensive analysis of global DNA methylation alterations during experimental lingual carcinogenesis.Methods C57BL/6J mice were subjected to 16-week oral administration of 4-nitroquinoline-1-oxide(4NQO,50 mg/L).Lingual mucosa samples,being representative of normal tissue(week 0)and early(week 12)and advanced(week 28)tumorigen-esis,were harvested for microarray and methylated DNA immunoprecipitation sequencing(MeDIP-Seq).The mRNA and promoter methylation of transforming growth factor-beta-signaling protein 1(SMAD1)were evaluated with real-time quantitative reverse transcription polymerase chain reaction and Massarray in human lingual mucosa and tongue cancer cell lines.Results The cytosine guanine island(CGI)methylation level observed at 28 weeks surpassed that of both 12 weeks and 0 weeks.The promoter methylation level at 12 weeks exceeded that at 0 weeks.Notably,208 differentially expressed genes were negatively correlated to differential methylation in promoters among 0,12,and 28 weeks.The mRNA of SMAD1 was upregulated,con-current with a decrease in promoter methylation levels in cell lines compared to normal mucosa.Conclusion DNA methylation changed during lingual carcinogenesis.Overexpression of SMAD1 was correlated to promoter hypomethyl-ation in tongue cancer cell lines.

Hemophilic arthritis(HA),caused by recurrent bleeding,can seriously affect patient quality of life and consumes extensive social and medical resources.There is thus a need to establish an animal model of HA for research;however,this is limited by ethical requirements.Here we review the recent literature and summarize research progress into animal models of HA at home and abroad,from the aspects of species selection,modeling method,histopathology,and imaging evaluation method.Species selection includes rodents such as mice,New Zealand rabbits,beagles,miniature pigs,and crab-eating macaques.Modeling method comprise gene knockout trauma models,gene knockout spontaneous models,and injection models.Among these,the gene knockout spontaneous model closely mimics the pathological process of spontaneous bleeding and concurrent arthritis in human HA,making it more relevant to human HA.However,due to high modeling costs,phenotypic instability,and low survival rates,this model is not the preferred choice for animal experimental studies.In contrast,gene knockout trauma models exhibit characteristics such as short modeling time,strong stability,and high success rates,thus being widely utilized in animal experimental research.Evaluation of HA models involves various imaging method including MRI,micro-CT,MSKUS/PD,in addition to various gross scoring method.By reviewing the progress of HA model research,more experimental evidence is provided for investigating the pathogenesis and validating the efficacy of HA treatments,thereby compensating for the lack of clinical data,particularly in the field of traditional Chinese medicine therapy.

Objective:To study the application of scenario simulation teaching combined with modular training in nursing education of medical rescue in manned space flight.Methods:Twenty nurses from the medical rescue team of Strategic Support Force Characteristic Medical Center were selected as the research objects. The research objects were randomly divided into the scenario simulation combined with practical training group (practical training group, n=10) and traditional teaching group (control group, n=10). Scenario simulation teaching combined with modular training and traditional teaching were used to carry out nursing training. After the training, theoretical assessment, operation assessment and satisfaction survey were organized. Results:The scenario simulation teaching combined with modular training group was significantly better than the traditional training group in theory assessment, operation assessment and satisfaction survey of nursing staff (all P<0.05). Conclusions:Scenario simulation teaching combined with modular training has obvious teaching effect, which can improve the ability and quality of nursing staff, and help to complete the manned space medical rescue mission efficiently.

Objective:To review the characteristics and coping strategies of the rescue and landing medical support mission of Shenzhou-14 manned spacecraft.Methods:The characteristics of rescue and landing medical support mission of Shenzhou-14 manned spacecraft was analyzed, and the coping strategies and experience were discussed.Results:(1) The characteristics of rescue and landing medical support mission of Shenzhou-14 manned spacecraft included: long time in space station and high-intensity space missions; high-density space medical support mission in short term; special environmental factors in severe cold night; complex terrain of landing site; and the young medical support team. (2) The main coping strategies of rescue and landing medical support mission of Shenzhou-14 manned spacecraft included: strengthened the organization and leadership and improved the training model; reinforcement learning the medical treatment plan and strengthened the medical rescue skills training; optimized the carrying equipment and added the heat preservation and lighting measures; improved the medical rescue process and perfected the emergency plan; emphasized on the scientific research as important as mission; and strengthened the physical exercise and cold resistance exercise.Conclusions:The characteristics and coping strategies of rescue and landing medical support mission of Shenzhou-14 manned spacecraft are summarized to provide the experience for space medical rescue and offer the support for China's manned space industry.

Objective:To compare perioperative differences between posterior lumbar interbody fusion(PLIF)by a posterior median approach or open transforaminal lumbar interbody fusion(TLIF)and minimally invasive surgery TLIF(MIS-TLIF)by a paravertebral approach for lumbar spondylolisthesis(Ⅰ~Ⅱ°)in elderly patients.Methods:A retrospective study was conducted to analyze clinical data of patients aged 60 years and over with lumbar spondylolisthesis(n=68)who underwent PLIF or MIS-TLIF from January 2014 to December 2017.Patients were divided into the PLIF group(n=40, 12 males and 28 females)and the MIS-TLIF group(n=28, 6 males and 22 females)according to the type of surgery.Differences in operating time, blood loss, exposure frequency, postoperative drainage volume, indwelling duration, hospital stay length and complications were compared between the groups.Results:There was no significant difference in operative time between the PLIF group and the MIS-TLIF group(156±51)min vs.(153±38)min( P=0.77). There were significant differences in intraoperative blood loss and radiation exposure frequency between the PLIF group and the MIS-TLIF group(458±272)ml vs.(157±104)ml( P<0.001); (6.7±1.5)times vs.(30.6±6.9)times( P<0.01). There was no significant difference in intraoperative complications between the PLIF group and the MIS-TLIF group(25% or 10/40 vs.7.1% or 2/28, P=0.057). There were more postoperative drainage, longer indwelling time and hospitalization in the PLIF group than in the MIS-TLIF group(664±351)ml vs.(210±127)ml( P<0.001); (3.7±2.9)d vs.(2.2±0.8)d( P=0.002); (9.2±3.6)d vs.(6.9±1.7)d( P=0.001). The incidence of postoperative neurological complications was not significantly different between the PLIF group and the MIS-TLIF group(7.5% or 3/40 vs.14.3% or 4/28, P=0.365). The incidence of postoperative non-neurological complications was higher in the PLIF group than in the MIS-TLIF group(27.5% or 11/40 vs.7.1% or 2/28, P=0.036). Conclusions:Compared with PLIF, MIS-TLIF has the advantages of less intraoperative bleeding and postoperative drainage, shorter indwelling duration of urinary catheters, shorter hospital stays and fewer complications of non-neurological complications in treating Ⅰ-Ⅱ degree lumbar spondylolisthesis in the elderly, but it requires more radiation exposure.