Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry / 药物分析学报

Aconitine,a common and main toxic component of Aconitum,is toxic to the central nervous system.However,the mechanism of aconitine neurotoxicity is not yet clear.In this work,we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine.HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system.Meanwhile,to confirm the metabolic mechanism of aconitine toxicity on HT22 cells,the levels of lactate dehydrogenase,intracellular Ca2+,reactive oxygen species,glutathione and superoxide dismutase,and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology.Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid,which was followed by the accumulation of lactic acid and reduction of glucose.The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca2+overload and oxidative stress,and eventually result in cell apoptosis.In general,we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.

Application of endoscopic suturing instrument in laparoscopic gastrojejunostomy / 中华胃肠外科杂志

Objective: To investigate the safety and feasibility of using an endoscopic suturing instrument in laparoscopic gastrojejunostomy. Methods: A descriptive case series study was conducted to retrospectively analyze the clinical data of 5 patients with gastric cancer who underwent laparoscopic distal gastrectomy (Billroth II + Braun anastomosis) at Tangdu Hospital, Air Force Medical University from October 2022 to January 2023. The common opening was closed using an endoscopic suturing instrument. The indications were as follows: (1) patients aged between 18 and 80 years; (2) patients with gastric adenocarcinoma; (3) cTNM between I-III; (4) lower-third gastric cancer and radical gastrectomy is recommended; (5) no history of upper abdominal surgery (except for laparoscopic cholecystectomy). The surgery was performed as follows: A side-to-side gastrojejunostomy was performed with endoscopic linear cutter stapler. Then the common opening was closed with endoscopic suturing instrument. During suturing and closing the common opening, a vertical mattress suture was used to completely invert and close the mucosa-to-mucosa and serosa-to-serosa of the gastric and jejunum walls. After the first layer of suture was completed, the seromuscular layer was sutured from top to bottom to embed the common opening of stomach and jejunum. Results: Laparoscopic closure of the common gastrojejunal opening with endoscopic suturing instrument was successfully completed in all 5 patients. The operative time was (308.6±22.6) minutes, while the time of gastrojejunostomy was (15.4±3.1) minutes. The operative blood loss was (34.0±10.8) ml. No intraoperative or postoperative complications occurred in any of the patients. The first passage of gas occurred at (2.6±0.9) days, and the postoperative hospital stay was (7.0±1.9) days. Conclusion: The application of endoscopic suturing instrument in laparoscopic gastrojejunostomy is safe and feasible.

Clinical characteristics and genetic analysis of a child with Galactosemia due to compound heterozygous variants of GALT gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic basis of a child with Galactosemia.@*METHODS@#A child who had presented at the Children's Hospital Affiliated to Zhengzhou University on November 20, 2019 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variants were validated by Sanger sequencing.@*RESULTS@#Clinical manifestations of the child have included anemia, feeding difficulty, jaundice, hypomyotonia, abnormal liver function and coagulation abnormality. Tandem mass spectrometry showed increased citrulline, methionine, ornithine and tyrosine. Urine organic acid analysis showed increased phenyllactic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvate and N-acetyltyrosine. Genetic testing revealed that the child has harbored compound heterozygous variants of the GALT gene, namely c.627T>A (p.Y209*) and c.370G>C (p.G124R), which were respectively inherited from her healthy parents. Among these, c.627T>A (p.Y209*) was known as a likely pathogenic variant, while c.370G>C (p. G124R) was unreported previously and also predicted as a likely pathogenic variant(PM1+PM2_Supporting+PP3_Moderate+PPR).@*CONCLUSION@#Above discovery has expanded the spectrum of the GALT gene variants underlying Galactosemia. Patients with thrombocytopenia, feeding difficulties, jaundice, abnormal liver function and coagulation abnormality without obvious causes should be analyzed by screening of metabolic diseases in combination with genetic testing.

Analysis of clinical characteristics and ACADM gene variants in four children with Medium chain acyl-CoA dehydrogenase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of four patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD).@*METHODS@#Four children who had presented at the Children's Hospital Affiliated to Zhengzhou University between August 2019 and August 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to whole exome sequencing (WES).@*RESULTS@#All of the four children were diagnosed with MCADD. Blood amino acid and ester acyl carnitine spectrum test showed that the concentration of octanoyl carnitine (C8) was significantly increased. The main clinical manifestations included poor mental response (3 cases), intermittent diarrhea with abdominal pain (1 case), vomiting (1 case), increased transaminase (3 cases), and metabolic acidosis (2 cases). Five variants were identified by genetic testing, among which c.341A>G (p.Y114C) was unreported previously. Three were missense variants, one was frameshift variant and one was splicing variant.@*CONCLUSION@#The clinical heterogeneity of MCADD is obvious, and the severity of the disease may vary. WES can assist with the diagnosis. Delineation of the clinical symptoms and genetic characteristics of the disease can facilitate early diagnosis and treatment of the disease.

Research progress of the regulatory role of autophagy in metabolic liver diseases / 中华肝脏病杂志

Autophagy is one of several hepatic metabolic processes in which starved cells are supplied with glucose, free fatty acids, and amino acids to produce energy and synthesize new macromolecules. Moreover, it regulates the quantity and quality of mitochondria and other organelles. As the liver is a vital metabolic organ, specific forms of autophagy are necessary for maintaining liver homeostasis. Protein, fat, and sugar are the three primary nutrients that can be altered by different metabolic liver diseases. Drugs that have an effect on autophagy can either promote or inhibit autophagy, and as a result, it can either increase or inhibit the three major nutritional metabolisms that are affected by liver disease. Thus, this opens up a novel therapeutic option for liver disease.

Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability.@*METHODS@#Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05).@*CONCLUSION@#Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.

Exploring occupational hazards and protective strategies in power generation enterprises / 中国职业医学

Currently, power generation in China is dominated by thermal power, wind power, nuclear power, and hydropower enterprises. The power source mainly comes from thermal power generation. The occupational hazards in thermal power station are noise, high temperature, power frequency electric fields, dust, and chemical toxins and so on, with noise and dust (silica and coal dust) being the primary factors. The occupational hazards in wind power station are noise, power frequency electric fields, high temperature, low temperature, and chemical toxins (sulfur hexafluoride, toluene, styrene, etc.), with noise and power frequency electric fields being the major concerns. The occupational radiation hazards in nuclear power station are gamma rays, beta rays, X-rays, neutrons, alpha rays, and radioactive aerosols. There is special attention in radiation protection but not enough protection in non-radioactive hazards such as noise, high temperature, and ammonia. The occupational hazards in hydropower station are noise, power frequency electric fields, vibration, radon and its de-composites, and chemical toxins, with noise and power frequency electric fields being the primary hazards. Different categories of power generation enterprises should identify key hazards and work site for occupational disease prevention and control based on the features of occupational hazards. Improving occupational health management and protection levels are essential measures.

Research on the lncRNA MALAT1 promoting the proliferation, migration and angiogenesis of retinal vascular endothelial cells in diabetic retinopathy through the molecular axis of miR-124-3p/SOX7 / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of lncRNA MALAT1 on the proliferation, migration and angiogenesis of retinal vascular endothelial cells and its molecular mechanism.METHODS: The expression levels of lncRNA MALAT1 in plasma of normal control group, diabetic without retinopathy group and diabetic retinopathy group were detected by qPCR and the effect of glucose culture on the expression levels of lncRNA MALAT1 were detected by qPCR too. The expression level of miR-124-3p was detected by qRT-PCR; Western blotting was used to detect the expression level of SOX7; The targeting relationship between lncRNA MALAT1 and miR-124-3p, miR-124-3p and SOX7 were detected by the dual-luciferase reporter system; CCK-8 assay was used to detect cell proliferation activity; Transwell assay was used to detect the migration ability of cells; Angiogenesis of hRMECs cells was measured by in vitro tube formation assay.RESULTS:The expression level of lncRNA MALAT1 in plasma of diabetic retinopathy patients was significantly higher than that of diabetic without retinopathy group and normal control group(P&#x003C;0.001). In vitro glucose culture significantly promoted the expression of lncRNA MALAT1 in hRMECs cells, as well as the proliferation, migration and angiogenesis of hRMECs cells(all P&#x003C;0.05). Knockdown of lncRNA MALAT1 significantly inhibited the proliferation, migration and tubule formation of hRMECs cells(all P&#x003C;0.05). Dual-luciferase reporter gene assay showed that lncRNA MALAT1 targeted with miR-124-3p, and miR-124-3p targeted with SOX7. Overexpression of miR-124-3p significantly inhibited the proliferation, migration and tubule formation of hRMECs cells(all P&#x003C;0.05). Overexpression of lncRNA MALAT1+miR-124-3p, miR-124-3p+SOX7, and knockdown of lncRNA MALAT1+overexpression of SOX7 all significantly eliminated the inhibitory effect of hRMECs cells(all P&#x003C;0.05).CONCLUSION: lncRNA MALAT1 promote the proliferation, migration and angiogenesis of retinal endothelial cells in diabetic retinopathy by down-regulating the negative regulation of miR-124-3p on SOX7. Therefore, abnormal upregulation of lncRNA MALAT1 in patients with diabetic retinopathy is a potential biomarker.

Childhood onset spinocerebellar ataxia type 2: a family report and literature review / 中华神经科杂志

Objective:To investigate the clinical characteristics, genetic characteristics and diagnosis of spinocerebellar ataxia type 2 (SCA2) patients with childhood onset.Methods:The clinical data of a SCA2 pedigree who diagnosed at Neurogenetic Metabolic Disease Clinic of Children′s Hospital Affiliated to Zhengzhou University in July 2019 were collected, and the reported cases of childhood-onset SCA2 were reviewed. The CAG repeat of ATXN2 gene was detected by polymerase chain reaction, capillary gel electrophoresis and Sanger sequencing techniques.Results:A total of 9 people in 4 generations of the family were affected, showing an autosomal dominant inheritance. The proband was a 3 years and 4 months old boy, who showed abnormal symptoms at 9 months which manifested as developmental retardation. At 1 year old, he developed progressive regression which represented neither to be amused, recognize others, stand and walk alone, nor had language development. Meanwhile, he had difficulty swallowing, long-term constipation, and a history of convulsions. His sister and mother were not yet sick. His grandmother could not walk, had slurred speech accompanied by nystagmus, and magnetic resonance imaging showed cerebellar atrophy. His granduncles and grandaunts had unstable walking and dysarthria. His great-grandfather required wheelchair to walk. This pedigree showed an autosomal dominant inheritance. One of the ATXN2 gene alleles of the proband, his sister, mother and grandmother all showed abnormal amplification with 99, 55, 44, and 43 times respectively and no inserting CAA sequence. A total of 14 literatures reported 20 cases of childhood-onset SCA2 patients who were genetically diagnosed. The majorities had onset in infancy, and few can develop into school age. The main clinical manifestations were developmental delay, dystonia or insufficiency, myoclonus or infantile spasms, motor retardation, abnormal eye movement, retinitis pigmentosa and dysphagia, while the classic cerebellar syndrome was only partially present. Abnormal rhythm was found on electroencephalogram, cerebellar atrophy on magnetic resonance imaging or CT of the head.Conclusions:This case is the youngest genetically-confirmed SCA2 patient reported in China. Reported patients usually have onset in infancy with excessive repeat sequence expansion. Their clinical characteristics are different from the classic patients and could only be diagnosed by dynamic mutation detection.

Correlation analysis of Traditional Chinese Medicine physical fitness and cardiovascular health behaviors among college students / 中国学校卫生

Objective@#To analyze the correlation between Traditional Chinese Medicine (TCM) physical fitness and cardiovascular health behaviors among college students and to provide a reference for physical fitness management and primary prevention of cardiovascular diseases for college population.@*Methods@#From August to November 2021, 1 621 college students from three universities in Liaoning Province were selected by clustering random sampling method, and questionnaire survey was conducted using the TCM Physical Fitness Determination Scale and the cardiovascular health behavior index proposed by the American Heart Association to analyze the correlation between TCM physical fitness and cardiovascular health behavior among college students.@*Results@#Cigarette smoking was higher among male students (20.7%) and students majoring arts and sports(27.3%)( χ 2=184.99, 79.43, P < 0.05). Body mass index (BMI) was higher among male students (4.7%) and students majoring medicine(3.6%)( χ 2=64.11, 15.38 , P <0.05). Physical inactivity was more common among female students(39.6%), medical majors(45.2%), and students with a family history of cardiovascular disease(CVD)(33.4%)( χ 2=145.40, 189.91, 15.89, P <0.05). Unhealthy diet was more common among students with medical majors and no family history of CVD(45.8%, 43.1%)( χ 2=33.13, 15.57, P <0.05). Significant differences in TCM body composition were found among college students by gender, major, and family history of CVD( χ 2=101.22, 82.38, 90.42, P <0.01). Healthy diet (ideal) and physical exercise (ideal, average) were negatively associated with Qi deficiency ( OR =0.48, 0.19, 0.63), physical exercise (ideal, average) was negatively associated with Yang deficiency( OR =0.43, 0.68), BMI (ideal) and physical exercise (ideal) were negatively associated with Phlegm dampness( OR =0.21, 0.37), physical exercise (ideal) was negatively correlated with Damp heat and Blood stasis qualities ( OR =0.34, 0.20), and physical exercise (ideal, general) was negatively correlated with Qi yu qualities( OR =0.34, 0.51)( P <0.05).@*Conclusion@#TCM physical fitness is associated with cardiovascular health behavior, with varying effects of each indicator of cardiovascular health behavior on TCM physical fitness. Personalized cardiovascular interventions should be taken according to differential constitutions to provide reference for constitution regulation and cardiovascular disease prevention.

Research progress of obstructive sleep apnea hypopnea syndrome and ocular surface diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Obstructive sleep apnea hypopnea syndrome(OSAHS)is a group of diseases which occurred in the upper respiratory tract with transient, recurrent, partial or complete obstruction during night sleep. It can affect the regulation of hemodynamics, endocrine systems and autonomic nerve, and then result in the reduction of body oxygen saturation, chronic hypoxia and hypercapnia. Beside being an independent risk factor for cardiovascular and cerebrovascular diseases, many studies have shown that it is also associated with ocular surface diseases in OSAHS, such as floppy eyelid syndrome, dry eye, keratoconus, etc., but there is still a lack of perfect systematic analysis. This paper reviews the relationship between OSAHS and relevant ocular surface diseases including pathogenesis,clinical manifestations and treatment progress, in order to reduce the ophthalmic complications of OSAHS patients in clinical diagnosis and treatment,and better improve the quality of life of patients.

FU Wen-bin's experience in treatment of depression complicated with obsessive-compulsive disorder from perspective of heart and gallbladder / 中国针灸

Based on the thinking of integrative and holistic acupuncture and moxibustion, FU Wen -bin proposes to treat depression complicated with obsessive-compulsive disorder from perspective of heart and gallbladder. In clinical practice, the treatment pattern of "acupuncture at the top priority, followed by moxibustion, and consolidation at the end" is applied, acupuncture, refined moxibustion, intradermal needle and other therapies are comprehensively adopted, acupoints on the heart meridian, pericardium meridian and gallbladder meridian are selected or back-shu points and front-mu points of the heart, gallbladder and pericardium are matched, and the acupoints on the conception vessel and governor vessel and with the functions of tonifying kidney and regulating qi are added to calm the heart and tranquilize the mind, so as the symptoms of depression and obsessive-compulsive can be effectively relieved.

Clinical characteristics and literature review of a case of Christianson syndrome caused by SLC9A6 gene variation / 中华神经科杂志

Objective:To retrospectively analyze the clinical data of Christianson syndrome caused by SLC9A6 gene mutation and related literatures.Methods:The clinical data of one Christianson syndrome patient caused by SLC9A6 gene variation in Children′s Hospital of Zhengzhou University were collected, meanwhile the relevant literature was reviewed. The examination of video electroencephalogram, auditory brainstem response, and cranial magnetic resonance imaging (MRI) was performed. Whole exon sequencing and mitochondrial gene detection were performed for 3 persons in the family, and the suspected mutation sites were verified by Sanger sequencing.Results:A boy, 7 years old, presented with epilepsy, language retardation and mental retardation. Now he can only say overlapping words, execute simple instructions, denying family history of genetic disease and genetic metabolic disease. The patient′s uncle had the history of febrile convulsions in childhood. At present, speech and intelligence are impaired, and the left limb movement is slightly limited. The patient′s mother was mildly retarded, without epilepsy. The video- electroencephalogram of the patient was shown below (April 2021): abnormal electroencephalogram; background activity was slightly slow; the bilateral frontotemporal region was dominated by multi-focal spiky wave, spiky slow wave and slow wave in each waking and sleeping stage, which can be generalized and extensive; in the sleeping stage, the discharge index in non-rapid eye movement stage was about 75%. The auditory brainstem response was shown below (October 2021): the left 70 dB Ⅰwave latency was prolonged; the Ⅰwave Ⅴ wave shape was poor; the threshold was 20 dB (the high frequency threshold was normal); the right 70 dB Ⅰwave latency was prolonged; the wave form was poor; the amplitude was lower than that of the contralateral side; Ⅲ wave Ⅴ wave shape was poor; the threshold was 30 dB (the high frequency threshold slightly increased). Brain MRI thin-section scan was shown below (January 2021): subarachnoid space of bilateral temporal poles widened, and no obvious abnormal signal was found in brain parenchyma; sinusitis. Whole exome sequencing of 3 persons in the family indicated that the proband had a hemizygous variant c.616C>T (p.R206 *) in the SLC9A6 gene. Using the SLC9A6 gene and Christianson syndrome as the key words, 94 foreign literatures from January 1989 to January 2022 were researched. Totally, 81 Christianson syndrome patients caused by SLC9A6 gene mutation were reported. The age of onset ranged from neonatal period to adulthood, and the clinical manifestations were heterogeneous. The symptoms of male patients mainly included epilepsy, severe cognitive impairment, ataxia, cerebellar atrophy, and psychomotor retardation. Conclusions:The hemizygous variant of SLC9A6 gene (c.616C>T) is the etiology of this patient. The possibility of Christianson syndrome shall be considered for recurrent epilepsy with poor efficacy of antiepileptic drugs, status epilepticus during slow-wave sleep, and delayed development of motor intelligence. Genetic testing is helpful for definite diagnosis and treatment.

Coactivator p300-induced H3K27 acetylation mediates lipopolysaccharide-induced inflammatory mediator synthesis / 南方医科大学学报

OBJECTIVE@#To investigate the role of acetylated modification induced by coactivator p300 in lipopolysaccharide (LPS)- induced inflammatory mediator synthesis and its molecular mechanism.@*METHODS@#Agilent SurePrint G3 Mouse Gene Expression V2 microarray chip and Western blotting were used to screen the molecules whose expression levels in mouse macrophages (RAW246.7) were correlated with the stimulation intensity of LPS. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (chip-qPCR) were used to verify the binding of the molecules to the promoters of IL-6 and TNF-α genes. The effects of transfection of RAW246.7 cells with overexpression or interfering plasmids on IL-6 and TNF-α synthesis were evaluated with ELISA, and the binding level of the target molecules and acetylation level of H3K27 in the promoter region of IL-6 and TNF-α genes were analyzed by chromatin immunoprecipitation sequencing technique (chip-seq).@*RESULTS@#Gene microarray chip data and Western blotting both confirmed a strong correlation of p300 expression with the stimulation intensity of LPS. Immunocoprecipitation confirmed the binding between p300 and c-myb. The results of EMSA demonstrated that c-myb (P < 0.05), but not p300, could directly bind to the promoter region of IL-6 and TNF-α genes; p300 could bind to the promoters only in the presence of c-myb (P < 0.05). The expressions of p65, p300 and c-myb did not show interactions. Both p300 overexpression and LPS stimulation could increase the level of promoter-binding p300 and H3K27 acetylation level, thus promoting p65 binding and inflammatory gene transcription; such effects were obviously suppressed by interference of c-myb expression (P < 0.05). Interference of p65 resulted in inhibition of p65 binding to the promoters and gene transcription (P < 0.05) without affecting p300 binding or H3K27 acetylation level.@*CONCLUSION@#LPS can stimulate the synthesis of p300, whose binding to the promoter region of inflammatory genes via c-myb facilitates the cohesion of p65 by inducing H3K27 acetylation, thus promoting the expression of the inflammatory genes.

Overlap esophagojejunostomy with multi-mode modifications in totally laparoscopic total gastrectomy: safety and feasibility of 152 cases from a single center / 中华胃肠外科杂志

Objective: Currently, the Overlap anastomosis is one of the most favored reconstruction methods of intracorporeal esophagojejunostomy (EJS). Despite many advantages of the method, it remains some shortcomings to be improved when it comes to the retraction of the esophagus stump, the insertion of the anvil fork of the linear stapler into a "pseudo" lumen, and the closure of the common entry hole. This study aims to investigate the safety and feasibility of a multi-mode modified Overlap anastomosis. Methods: A descriptive case series study was conducted. Medical records of 152 consecutive patients who underwent totally laparoscopic total gastrectomy (TLTG) with our multi-mode modified Overlap EJS method by the same surgical team at our department from February 2017 to June 2020 were retrospectively analyzed. The multi-mode modified Overlap method mainly included (1) After ensuring the safety of tumor resection margin (proximal margin was at least 3 cm from the tumor), the esophagus was partially transected from left to right (with 5-8 mm width esophagus continuation). The specimen was then placed in a plastic bag which was tied up at the mouth using strings with a part of the esophageal wall poking through. Then the plastic bag containing the specimen was transferred to the right lumbar region, while the patient's body position was adjusted so that the abdominal esophagus could be pulled by the gravity of the specimen. (2) Using the "three-direction traction" method. The esophageal lumen was properly exposed, then guided by the gastric tube, the anvil fork was accurately placed into the esophageal lumen for completing the side-to-side EJS. (3) The 3-0 barbed suture was used in the closure of the common entry hole of the stapler from dorsally to ventrally with simple one-layer continuous suture (the stitch going from inside to inside) followed by continuous Lembert's suture (the stitch going from outside to outside). Combined with clinicopathological characteristics, the perioperative outcomes and postoperative complications of the whole group were analyzed and evaluated. Results: The study cohort included 129 men and 23 women, with a mean age of (60.2±9.1) years and a mean body mass index (BMI) of (23.2±3.1) kg/m(2). Of the 152 patients, 23 patients (15.1%) had a history of previous abdominal surgery; dentate line was invaded by tumor in 21 patients (13.8%). The mean length of the proximal resection margin was (3.3±0.3) cm and the postoperative pathological examination indicated negative resection margin tumor. The mean operative time and anastomotic time were (302.1±39.9) minutes and (29.8±5.4) minutes, respectively. The mean estimated blood loss was (87.9±46.4) ml. The mean length of postoperative hospital stay was (12.3±7.3) days. The overall severe postoperative complications (Clavien-Dindo ≥ II) occurred in 22 patients (14.5%). Six cases of pancreatic leakage were successfully recovered by adequate drainage, inhibition of pancreatic exocrine secretion and nutritional support. Ten cases of pneumonia and three cases of abdominal infection were cured with anti-infection and physical therapy. Two patients developed anastomotic leakage postoperatively. One case was caused by excessive tension of the Roux loop of the jejunum and excessive opening on the side of the jejunum after side-to-side anastomosis, and the other case was caused by an accidental intraoperative occurrence of "nasogastric tube stapled to the side-to-side anastomosis". Both of them recovered after conservative treatment including adequate drainage, anti-infection, and adequate nutritional support. One patient underwent immediate open surgery because of Peterson's hernia 7 days after TLTG, and the patient died due to extensive small bowel necrosis. Conclusions: Multi-mode modified overlap method simplifies the operation and reduces the difficulty of EJS. It is a safe and feasible method for EJS.

Technical details of gastrointestinal reconstruction using linear stapler in totally laparoscopic total gastrectomy / 中华胃肠外科杂志

With the development of instrument, equipment and surgical skills, especially the emergence of a series of high-level medical evidence, the laparoscopic techniques in the field of gastric surgery has been further expanded. Totally laparoscopic total gastrectomy (TLTG) has certain technical difficulties, and more challenges are reflected in the digestive tract reconstruction. The use of linear staplers has reduced the difficulty of digestive tract reconstruction to a certain extent and has strongly promoted the transition from laparoscopic-assisted total gastrectomy to TLTG. However, for TLTG, there are still many details that should be carefully concerned, so as to effectively avoid the surgical pitfalls and ensure the fluency and safety of the procedure. In this article, we discuss the surgical details based on our own experiences, including how to obtain surgical field exposure well, how to manage specific accidents when using linear stapler for esophagojejunostomy, how to prevent intra-abdominal hernias and Roux stasis syndrome, and how to prevent the stapled lines of the esophageal or jejunal stumps from direct contact with aorta.

A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data / 中华胃肠外科杂志

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Diterpenoid alkaloids from roots of Aconitum kongboense / 中国中药杂志

The chemical constituents from the roots of Aconitum kongboense were studied. Twenty-five diterpenoid alkaloids were isolated from the 95% methanol extract of the roots of A. kongboense by silica gel, reverse-phase silica gel and basic alumina column chromatography. They included a new aconitine-type diterpenoid alkaloid, named as kongboensenine(1), and twenty-four known ones(2-25), i.e., acotarine F(2), acotarine G(3), 14-acetyltalatisamine(4), talatisamine(5), indaconitine(6), yunaconitine(7), chasmanine(8), 6-epi-foresticine(9), homochasmanine(10), 8-deacetyl-yunaconitine(11), chasmaconitine(12), ajaconine(13), franchetine(14), ezochasmanine(15), crassicautine(16), 14-O-deacylcrassicausine(17), genicunine A(18), falconeridine(19), sachaconitine(20), liljestrandisine(21), 8-methyl-14-acetyltalatisamine(22), kongboendine(23), 14-benzoylchasmanine(24) and pseudaconine(25). Their structures were elucidated by common spectroscopic methods including high-resolution electrospray ionization mass spectrometry(HR-ESI-MS) and nuclear magnetic resonance(NMR) techniques. Compounds 2-4, 10, 13, 15-19 and 21-22 were isolated from this plant for the first time. Experimental results showed that all compounds did not have a significant inhibitory activity against acetylcholinesterase(AChE).

3-Hydroxy-isobutyryl-coenzyme A hydrolase deficiency: a case report and literature review / 中华神经科杂志

Objective:To analyze the characteristics of clinical manifestation, auxiliary examination and gene mutation of 3-hydroxy-isobutyryl-coenzyme A hydrolase (HIBCH) deficiency to better understand this disease.Methods:The clinical manifestations and genetic results of a patient with HIBCH deficiency were analyzed. The clinical features and genetic characteristics of HIBCH deficiency were summarized based on the literature review.Results:The proband, female, one year and four months old, was admitted to Children′s Hospital Affiliated to Zhengzhou University for “vomiting and diarrhea for 15 days, dyspnea and intermittent convulsions for 13 days after digestive tract infection”. The intelligence was normal, however, the motor development was slightly delayed before onset. Physical examination showed light coma, poor response and insensitivity to light. She also had shortness of breath, weak positive three concave signs and coarse breath sound in both lungs with sputum purrs. In addition, the muscle tension of extremities was increased. Bilateral Brudzinski′s sign, Babinski′s sign and Kernig′s sign were negative. Serum hydroxybutyryl carnitine (C4OH) was increased. Cranial magnetic resonance imaging (MRI) showed atrophy in bilateral cerebral hemispheres and abnormal symmetry signals in bilateral globus pallidus and cerebral peduncle. Novel compound heterozygous variants of HIBCH, c.489T>A (p. C163*) and c.740A>G (p. Y247C), were found in the patient, which respectively inherited from her healthy parents. Her symptoms were relieved after“cocktail”therapy and symptomatic treatment. Literature related to HIBCH deficiency published all around the world was reviewed. As a result, 17 articles, including 24 cases, had been reported. The majority of patients presented with poor feeding, dystonia and progressive motor developmental delay in early infancy. Cranial MRI showed lesions in bilateral basal ganglia. Serum C4OH concentration was elevated. And compound heterozygous or homozygous variants of HIBCH gene were found in patients with HIBCH deficiency.Conclusions:The detection of serum amino acids and acylcarnitine profiles on HIBCH deficiency was relatively specific and it was helpful to make a clear diagnosis by combining with cranial MRI and genetic tests. In this study, a case of HIBCH deficiency was confirmed, which expanded the mutation spectrum of HIBCH gene. Meanwhile, summarizing the clinical and genetic characteristics of cases reported improved understanding of HIBCH deficiency.

Advances development of 64CuCl 2 in the diagnosis and treatment of tumor and disease of abnormal copper metabolism / 中华核医学与分子影像杂志

Copper is an essential metal element for human metabolism. Copper homeostasis can lead to inherited disorders of copper metabolism and also play an important role in tumor proliferation. In recent years, great progress has been made in the research and development of radioactive metal nuclide tracers, and molecular imaging quickly becomes a new inspection technology for detecting copper metabolism. 64CuCl 2 carries out PET imaging diagnosis of diseases with abnormal copper metabolism and tumors with high copper metabolism through real-time tracking of changes of copper ions in the body. At the same time, β - decay and electron capture of 64CuCl 2 have a therapeutic effect, and can be directly used for tumor nuclide therapy. Therefore, 64CuCl 2, as an integrated radiopharmaceutical for diagnosis and treatment, is the current research focus of molecular imaging. This article reviews 64CuCl 2 preparation, biological metabolism and its application in the diagnosis and treatment of abnormal copper metabolism diseases and tumors.