BACKGROUND:Clinical studies have shown that aerobic exercise is an important supplement to the clinical treatment of patients with pulmonary hypertension,which can alleviate the disease condition,increase exercise tolerance and improve the quality of life.However,it is not clear whether patients at different stages of pulmonary hypertension can benefit equally from exercise training. OBJECTIVE:To compare the intervention effects of early or late aerobic training on right heart failure in rats with pulmonary hypertension and explore its possible mechanism. METHODS:Sixty male Wistar rats were randomly divided into control group,model sedentary group,model early exercise group and model late exercise group,with 15 rats in each group.The model of pulmonary hypertension was established by intraperitoneal injection of monocrotaline(60 mg/kg)in the latter three groups.The model early exercise group was given 8 weeks of treadmill aerobic exercise(60%maximum running speed,60 minutes per day,5 days a week)after modeling,while the model late exercise group was trained for 6 weeks after 2 weeks of modeling.The control and model sedentary groups were fed quietly in the rat cage for 8 weeks.After training,the exercise performance,right ventricular hemodynamics,cardiopulmonary function,cardiopulmonary histopathology,reactive oxygen species level in mitochondria,activity of mitochondrial respiratory chain complex and expressions of myocardial tissue proteins were detected. RESULTS AND CONCLUSION:Compared with the model sedentary group,exercise performance and right ventricular function improved(P<0.05),myocardial collagen content,endothelin-1,tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio decreased(P<0.05),vascular endothelial growth factor and sarcoplasmic reticulum calcium-adenosine triphosphate enzyme expression increased(P<0.05),immunofluorescence intensity of mitochondrial reactive oxygen species and the protein expression of 3-nitrotyrosine decreased(P<0.05),the activities of complex I,II,IV and V increased in the model early exercise and model late exercise groups(P<0.05),but there were no significant changes in right ventricular maximum pressure,pulmonary acceleration time and pulmonary artery wall area/total vascular area ratio(P>0.05).Compared with the model late exercise group,the model early exercise group further improved exercise performance and right ventricular function,and downregulated collagen content,brain natriuretic peptide protein expression,tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio(P<0.05).To conclude,although pulmonary vascular remodeling and right ventricular overload persist in rats with pulmonary hypertension,exercise training at different stages of the disease has a cardioprotective effect.The mechanism is related to the improvement of cardiac remodeling,neurohormone system imbalance,inflammatory response and mitochondrial oxidative stress.Greater benefit is gained from initiating exercise in the early stage of the disease.

Objective To analyze the distribution of carbapenem-resistant strains and the transmission mode of resistance genes in the bacteria strains from urinary system of the individuals outside hospitals,and further explore the impacts of the antibiotics with different antibacterial mechanisms on the conjugation transfer of resistant plasmids.Methods The imipenem-resistant strains from 991 non-re-petitive urine samples of healthy individuals were screened for determining the carbapenem-resistance genotypes.Using the multilocus sequence typing(MLST)method,the main carbapenem-resistant strains were classified to determine the phylogenetic relationship be-tween different sequence types(STs)and reveal the transmission mode of resistance genes in the individuals outside hospitals.The conjugation experiment was used to analyze the effects of different sub-inhibitory concentrations of ampicillin,ciprofloxacin,and genta-micin on the conjugation efficiency of resistant plasmids in the bacteria of donor and/or recipient at different times.Results A total of 18 non-repetitive carbapenem-resistant strains(1.82％,18/991)were detected in healthy individuals outside hospitals,among which Escherichia coli(E.coli)(44.44％,8/18)was the main strain with main genotype being blaKPC-2(7/8).MLST showed that the 7 strains of E.coli with blaKPC-2 genotype belonged to ST-10,ST-101,ST-131,ST-405,ST-410,ST-1193,and ST-2562,respectively.Homologous clustering analysis showed that the type of the 7 E.coli strains exhibited high diversity.The range of joint efficiency was(1.59±0.20)× 10-4 to(4.01±1.31)× 10-4.The highest conjugation efficiency was observed in the donor bacteria treated with 1/8 of MIC of antibiotics for 9 hours,and the conjugation efficiency most significantly increased compared to the group without antibiotic treat-ment.Three antibiotics with different mechanisms of action could all improve conjugation efficiency,among which ampicillin exhibited the most significant improvement.Conclusion In this study,the genotype of carbapenem-resistant Escherichia coli(CREC)was mainly blaKPC-2 with a main mode of horizontal transmission.Antibiotics with sub-inhibitory concentrations could promote the conjugation transfer of the resistant plasmid.There may be significant differences in the effects of antibiotics with different mechanisms of action and different antibiotic stress conditions on the conjugation efficiency.

The incidence and detection rates of benign and low-grade malignant pancreatic tumors have risen yearly.For patients with such tumors,traditional radical resection procedures often result in excessive loss of normal pancreatic parenchyma,leading to complications such as postoperative insufficiency of both exocrine and endocrine functions.Studies have shown that functional-preserving surgeries,such as minimally invasive enucleation or partial resection surgeries,can maximize the protection of patients'pancreatic function and improve long-term quality of life.However,for some tumors deep within the pancreatic parenchyma,accurately locating the tumor and protecting the pancreatic duct pose challenges.Intraoperative ultrasound(IOUS)has become an ideal intraoperative imaging tool,often referred to as the surgeon's"third eye"because of its portability,ability to provide real-time high-resolution information,non-reliance on ionizing radiation,and the fact that it does not require special patient preparation.With advancements in technology,the application scope of IOUS has expanded beyond its initially limited diagnostic role to various surgical applications,including identifying non-palpable lesions,guiding surgical strategies,and staging tumors.In the current era of minimally invasive and precision surgery,the proficiency of surgeons in using IOUS has become an important issue.This article reviews the history of IOUS applications,summarizes the advantages and basic usage methods of robotic IOUS,and shares techniques for applying IOUS in robot-assisted precise resection of pancreatic tumors.

Objective To analyze the relationships of the expression of retinoid X receptor alpha (RXRA) and nuclear receptor interaction protein 1(NRIP1) in colorectal cancer tissues with the features of clinical pathology and prognosis. Methods A total of 106 specimens from colorectal cancer tissues of patients during surgery were included in colorectal cancer group (n=106), and corresponding paracancer tissue specimens were included in paracancer group (n=106). The expressions of RXRA and NRIP1 in colorectal cancer tissues were detected by immunohistochemistry. Multivariate Cox regression analysis was used to investigate th4e effects of RXRA and NRIP1 expressions on the prognosis of patients with colorectal cancer. Results The positive expression rates of RXRA and NRIP1 in colorectal cancer group were 66.04%, 69.81%, which were significantly higher than 33.96% and 30.19% in the para-cancer group (P < 0.05). The positive expression rates of RXRA and NRIP1 in patients with pathological stage Ⅲ, low differentiation, serous infiltration and lymph node metastasis were higher than those in patients with pathological stage Ⅱ, medium and high differentiation, no serous infiltration and lymph node metastasis (P < 0.05). The 3-year overall survival rates of patients with pathological stage Ⅱ, low differentiation, no serous infiltration, no lymph node metastasis, negative RXRA and NRIP1 were higher than those of patients with pathological stage Ⅲ, medium and high differentiation, serous infiltration, lymph node metastasis, positive RXRA and NRIP1 (P < 0.05). Multivariate Cox regression analysis showed serous membrane infiltration (HR=2.687; 95%CI, 1.531 to 3.156), positive RXRA (HR=3.743; 95%CI, 2.217 to 5.992), positive NRIP1 (HR=2.641; 95%CI, 1.124 to 4.757) were influencing factors for prognosis in patients with colorectal cancer (P < 0.05). Conclusion RXRA and NRIP1 are highly expressed in colorectal cancer, which are closely related to pathological stage, differentiation degree and metastasis, which can be used as biomarkers to assist in evaluating the prognosis of patients.

Objective:To evaluate the impact of vocal fold nodules on the quality of life of children, and to compare the efficacy between conservative management（voice hygiene education, etc.） and laryngeal microsurgery. Methods:A retrospective study was performed on 102 children with vocal fold nodules, who received treatment in Children's Hospital of Fudan University during the period from January 2020 to December 2022. According to the regime, the patients were divided into conservative management group and surgical treatment group; Cases are divided into pre-school age group （2-5 years old） and school-age group （6-12 years old） based on age. The pediatric voice-related quality of life （pVRQOL） was used to evaluate the impact of vocal fold nodules on the quality of life of children and differences in efficacy between two treatment regimens. Results:The pVRQOL scores of vocal fold nodule grades 1, 2, and 3 were 91.58±8.17, 78.87±12.49, 72.50±12.08, respectively. There were statistical differences between grade 1 and grade 2, and between grade 2 and grade 3. There were statistical differences between grade 1 grade 2, grade 2 and grade 3 （P<0.001）, suggesting that the higher the rating of vocal cord nodules, the lower the pVRQOL score of patients was. The pVRQOL score of the school-age group was 69.83±11.11, which is lower than that of the preschool group（87.59±8.63）, and the difference was statistically significant （P=0.042）. Vocal fold nodules had a significant impact on the pVRQOL score of school-age children. In the conservative management group, the pVRQOL scores before and after treatment were 83.99±12.66 and 87.26±9.58, respectively, and there was significant difference between the two groups（P=0.046）. Indirect voice therapy such as voice hygiene education could improve children's pVRQOL scores and was more effective for school-age children（P<0.001）. The microsurgical treatment had a more significant improvement in the pVRQOL score of children. Conclusion:The higher the rating of vocal fold nodules, the greater the impact on the quality of life of patients. Vocal fold nodules had a greater impact on the quality of life of school-age children than that of preschool children. Voice hygiene education could improve the quality of life of children, which was more evident in the school-age group. Compared with voice hygiene therapy, laryngeal microsurgery had a more significant effect on improving the pVRQOL score of patients. It is recommended to undergo laryngeal microsurgery for the treatment of vocal fold nodules for the requirement of improving the quality of life related to voice. During the 6-month follow-up period after surgery in this study, the short-term efficacy of laryngeal microsurgery in treating vocal cord nodules in children is clear, but the long-term efficacy needs further research.
Child ; Humans ; Child, Preschool ; Vocal Cords/pathology* ; Quality of Life ; Retrospective Studies ; Voice Quality ; Laryngeal Diseases/surgery* ; Polyps/pathology*

Laryngeal cyst is a cystic lesion occurring in the laryngeal cavity. Large laryngeal cyst in infants and young children can cause laryngeal wheezing and other upper airway obstruction symptoms. In severe cases, it can be even life-threatening and requires timely surgical treatment. Currently, there is a lack of unified clinical treatment strategy for this disease.This article summarizes the surgical methods, the advantages and disadvantages of various surgical methods for laryngeal cysts in recent years. It is recommended that needle aspiration, partial cyst wall resection, radical cyst dissection, transoral robotic surgery or external approach cyst resection should be selected through full communication and evaluation to clarify the extent of the lesion scope and the advantages and disadvantages of surgery.
Infant ; Child ; Humans ; Child, Preschool ; Cysts/diagnosis* ; Laryngeal Diseases/diagnosis* ; Larynx/surgery* ; Robotic Surgical Procedures ; Biopsy, Needle

With the popularity of electronic devices and the increasing environmental light pollution, more attention has been paid to the damage caused by retinal light irradiation and its pathogenic effects in retinal pigment degeneration, age-related macular degeneration and other diseases.The types of light-retinal tissue reaction are mainly photothermal and photochemical, and the photochemical reaction produced by visible light is closely related to retinal diseases.The parameters of light irradiation include wavelength, energy density and duration, etc.The effect of light irradiation on retinal cells can be influenced by many external factors under different parameters.Many in vitro models of light irradiation on retinal cells have been established to study the mechanism of light irradiation, especially blue light on retinal pigment epithelial cells, photoreceptor cells and nerve cells.Light irradiation can cause oxidative stress, endoplasmic reticulum stress and mitochondrial damage in retinal cells, which activates autophagy and regulates apoptosis.Inflammasome activation and exosomes are also involved in the regulation of light-induced damage to retinal pigment epithelial cells.There are also studies on the potential therapeutic effect of different wavelength light sources on cells.This review discusses the differences in cellular and light irradiation parameters between different models with respect to experimental models of retinal light irradiation in terms of types of light-retinal tissue responses, light irradiation parameters commonly used in biological studies, and retinal pigment epithelium light irradiation models, retinal photoreceptor light irradiation models, and retinal ganglion cell light irradiation models.

ObjectiveTo investigate the prevalence of overweight or obesity in community patients with schizophrenia in Shanghai and to explore the related factors. MethodsStratified cluster sampling method was used and the general condition， physical examination and laboratory examination data of patients with schizophrenia who voluntarily participated in 2020 free health examination of National Basic Public Health Service were analyzed. ResultsA total of 3 200 patients were included into the study ，and the prevalence of overweight and obesity was 36.75% and 17.19%， respectively. Multivariate logistic regression analysis indicated that age between 40 and 60 （OR=1.333， 95%CI： 1.030‒1.724）， intake of first-generation antipsychotics （OR=1.413， 95%CI： 1.112‒1.796）， intake of second-generation antipsychotics （OR=1.573， 95%CI： 1.288‒1.921）， high-normal blood pressure （OR=1.549， 95%CI： 1.245‒1.927）， high-abnormal blood pressure （OR=2.824， 95%CI： 2.204‒3.619）， elevated ALT （OR=1.874， 95%CI： 1.386‒2.535）， elevated FBG （OR=1.270， 95%CI： 1.066‒1.513）， and elevated TG （OR=1.652， 95%CI： 1.335‒2.044） were the related factors that associated overweight or obesity in patients with schizophrenia. ConclusionOverweight and obesity are highly prevalent among community patients with schizophrenia in Shanghai. Age between 40 and 60， taking first-generation and second-generation antipsychotics， blood pressure higher than 120/80 mmHg， elevated ALT， elevated FBG， and elevated TG are associated with overweight or obesity in patients with schizophrenia. To provide personalized health guidance， medical staff in primary health care institutions should pay more attention to high-risk groups of overweight and obesity in schizophrenia patients at annual physical examination.

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRAS^G12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFR^L858R and EGFR^Δ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‍‒‍1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‍‒‍2.63; P<0.0001), while classical activating mutations with EGFR^T790M showed no difference compared to classical activating mutations without EGFR^T790M in OS (adjusted HR, 0.96; 95% CI, 0.48‍‒‍1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‍‒‍1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‍‒‍0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‍‒‍0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‍‒‍8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‍‒‍6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRAS^G12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFR^T790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Extracellular Matrix Proteins/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Treatment Outcome

Objective:To investigate the management of patients with intravenous misplacement of nephrostomy tube following percutaneous renal surgery.Methods:The data of 6 patients with intravenous misplacement of nephrostomy tube during percutaneous nephrolithotomy (PCNL) treated in the two hospitals of Chenzhou from January 2006 to December 2020 were retrospectively analyzed. The median age was 41.0(38.5, 53.0) years old. There were 4 males and 2 females. Three patients had undergone contralateral upper urinary tract operation. One patient had undergone ipsilateral upper urinary tract operation. Two patients had not undergone upper urinary tract operation. Two of the 6 patients had a solitary kidney. Two patients were diagnosed with staghorn calculi (combined with mild hydronephrosis in 1 patient, moderate hydronephrosis in 1 patient). Four patients were diagnosed with ureteral calculus (combined with mild hydronephrosis in 2 patients, moderate hydronephrosis in 1 patient, severe hydronephrosis in 1 patient). In all 6 patients, the tract was dilated with fascial dilators. Immediately after dilator removal, brisk venous bleeding was noted. A nephrostomy tube was inserted promptly through the sheath to tamponade the tract and was immediately closed. Five cases were diagnosed by CT after operation, and 1 case was early diagnosed by intraoperative injection of contrast medium through nephrostomy tube. The nephrostomy tube was misplaced in 5 patients with left upper urinary tract calculi, and in 1 patient with right upper urinary tract calculi. The tip of nephrostomy tube was located in ipsilateral renal vein in 3 patients with left upper urinary tract calculus, inferior vena cava in 2 patients with left upper urinary tract calculus, and contralateral renal vein in 1 patient with right upper urinary tract calculus. No venous thrombosis of renal vein or inferior vena cava was founded in the 6 patients. All 6 patients were managed with strict bed rest, intravenous antibiotics, and one-step or two-step tube withdrawal under close monitoring. One step method referred to total removal of nephrostomy tube under ultrasonic monitoring. Two step method referred to retracting the end of nephrostomy tube into the renal sinus under CT monitoring in the first step, then the nephrostomy tube was completely removed under ultrasound monitoring.Results:All 6 patients were successfully managed with strict bed rest, intravenous antibiotics, and one-step or two-step tube withdrawal under close monitoring. The tube was withdrew by one-step method in 1 patient, by two-step method in 5 patients. The original operations were performed successfully under close observation in 4 patients during the same hospitalization and in 1 patient during the next hospitalization. Other type of operation in 1 patient was performed during the next hospitalization. The all 6 patients were discharged uneventfully. The stone was cleared.Conclusions:Intravenous misplacement of a nephrostomy tube is mainly diagnosed by CT. The nephrostomy tube should be sealed immediately after diagnosis. The intravenously misplaced nephrostomy tube can be successfully removed by one-step or two-step withdrawing under close monitoring. Upper urinary tract stones can be successfully treated at the same time or by stages.