Recent studies have identified that metabolic reprogramming in lung adenocarcinoma cells,particularly lactate metabolism disorders,plays a crucial role in tumor development and immune therapy response.The accumulation of lactic acid not only provides energy support for the proliferation of tumor cells but also affects the function of immune cells by changing the tumor microenvironment,thereby promoting immune escape.Immunotherapy,especially the application of immune checkpoint inhibitors,has become an important strategy for treating lung adenocarcinoma.However,lactate metabolism disorders might affect the efficacy of immunotherapy,leading to resistance in some patients.Therefore,a thorough understanding of the mechanisms of lactic acid metabolism in lung adenocarcinoma and its impact on the response to immu-notherapy is essential for developing new therapeutic strategies and improving the efficacy of immunoth-erapy.This review summarizes the role of lactate metabolism disorders in the development and immun-otherapy of lung adenocarcinoma,discusses the potential role of lactic acid metabolism-related genes and pathways in lung adenocarcinoma,and explores the progress in therapeutic strategies targeting lactic acid metabolism regulation.This work aims to provide new insights for the treatment of lung adenocarcinoma.

Background::Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown.Methods::A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen’s kappa test was used to assess the agreement between physicians and PLWH.Results::The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60-75.04%), and it is significantly different from the expected rate of 80% ( P <0.001). Similarly, the concordance rate for the evaluation of anxiety issues is 71.74% (95% CI: 70.47-72.97%), which is significantly different from the expected rate of 80% as per the null hypothesis ( P <0.001). The overestimation rate by physicians on depressive issues is 12.20% (95% CI: 11.32-13.14%), and for anxiety issues is 12.76% (95% CI: 11.86-13.71%). The mismatch rate for depressive issues is 26.16% (95% CI: 24.96-27.40%), and for anxiety issues is 28.26% (95% CI: 27.02-29.53%). The underestimation rate by physicians on depressive issues is 13.96% (95% CI: 13.03-14.95%), and for anxiety issues is 15.50% (95% CI: 14.52-16.53%). For the treatment regiments, PLWH sustained on innovative treatment regimen (IR) related to a lower prevalence of depressive issues (odds ratio [OR] = 0.71, 95% CI: 0.59-0.87, P = 0.003) and a lower prevalence of anxiety issues (OR = 0.63, 95% CI: 0.52-0.76, P <0.001). PLWH switch from conventional treatment regimen (CR) to IR also related to a lower prevalence of depressive issues (OR = 0.79, 95% CI: 0.64-0.98) and a lower prevalence of anxiety issues (OR = 0.81, 95% CI: 0.67-0.99). Conclusion::Nearly one in three PLWH had their condition misjudged by their physicians. The findings underscore the need for improved communication and standardized assessment protocols in the care of PLWH, especially during the acute phase of HIV infection.

Objective:To explore the risk factors of recurrence after resection of thigh soft tissue malignant tumors and the evaluation of the postoperative lower limb function.Methods:A total of 211 patients who underwent thigh soft tissue malignant tumor resection in the Department of Orthopaedics of the second affiliated Hospital of Medical College of Zhejiang University from May 2011 to May 2021 were retrospectively analyzed, including 117 males and 94 females, aged 53 (43, 65) years. There were 59 cases of atypical/well-differentiated liposarcoma, 30 cases of other types of liposarcoma, 33 cases of malignant fibrous histiocytoma, 19 cases of fibrosarcoma, 12 cases of rhabdomyosarcoma, 12 cases of leiomyosarcoma, 9 cases of synovial sarcoma, and 37 cases of others. The tumor involvement of muscle, bone, blood vessel, nerve tissue and intermuscular compartment, postoperative Musculoskeletal Tumor Society (MSTS) functional score and recurrence were recorded. The relationship between anatomical structure and postoperative recurrence was analyzed by Cox logistic regression to determine risk factors; the cumulative recurrence rate of different compartment groups (medial compartment, anterior compartment, and posterior compartment) were compared; The Box plot was used to compare the postoperative function of patients with resection of different anatomical structures (e.g., vastus lateralis, biceps femoris, femur, etc.).Results:A total of 34 out of 211 patients relapsed, with a recurrence rate of 16.1%. The recurrence time ranged from 2.6 months to 91.6 months after operation, with a median recurrence time of 37.0 (18.2, 52.8) months. Three independent risk factors were found to be associated with recurrence, namely: pathological grade [ HR=3.86, 95% CI(1.75, 8.51)], involvement of vastus intermedius [ HR=3.05, 95% CI(1.53, 6.06)], and involvement of vastus medialis [ HR=3.17, 95% CI(1.56, 6.41)]. The recurrence rate of patients with anterior chamber tumor resection was 35.3%, which was higher than that of patients without tumor resection (16.2%), and the difference was statistically significant ( P=0.020). There was no significant difference in recurrence rate between patients with medial chamber tumor resection and patients without tumor resection ( P>0.05). The recurrence rate of patients with posterior compartment tumor resection was 12.3%, which was lower than that of unresectable patients (37.6%), and the difference was statistically significant ( P=0.002).The postoperative MSTS score of 167 patients averaged 26±3.2 points (9-30 points). After intraoperative resection of part of the femur, vastus intermedius, vastus medialis, and rectus femoris, the patient's function was relatively poor [corresponding median MSTS score: 25 (23, 28), 26 (24 28), 26 (24,28), 26(24, 27)]. Conclusion:The risk factors for local recurrence after resection of thigh soft tissue malignant tumors include: pathological grade of the tumor, and whether the vastus intermedius or vastus medialis is involved. Anterior compartment tumors have a higher recurrence rate after surgery. If the tumor involves the above-mentioned anatomical structures, more attention should be paid to the risk of local recurrence after surgery.

[Abstract] Objective: To screen candidate epitopes of breast cancer HLA-A2 restrictive neoantigen and to identify high frequency mutation sites in breast cancer neoantigen by using bioinformatics method. Methods: NCBI and GDC databases were used to search missense mutation sites formed by single nucleotide mutation in breast cancer among reported literatures and sequencing data. The new antigen epitopes were predicted by HLA-A2 antigen epitope prediction website BIMAS, SYFPEITHI and artificial neural networkbased NetMHC4.0, and the epitopes with TAP binding power less than Intermediate were eliminated. The candidate epitopes were prioritized by mutation frequency and prediction results. Results: A total of 17 high-frequency mutation genes, including BTLA, ERBB2 and NBPF12 etc, were screened by the above-mentioned methods, and a total of 26 neoantigen epitopes were identified. The binding power of epitopes predicted using BIMAS and SYFPEITHI showed great difference (P<0.05), epitopes in high priority as GSTP1 (A114V , mutation frequency of 5.94%) and BRCA2 (N991H, mutation frequency of 5.40%) etc, were expected to be candidate neo-antigen epitopes; however, their mutation frequency was relatively too low to achieve“universal use” . The possibility of these epitopes used as general breast cancer neo-antigen epitopes is less likely. Conclusion: The common mutation frequency of breast cancer is lower than that of other tumors; it ’s difficult to find“universal”new antigen epitopes of breast cancer; the individualized neoantigen vaccine may be of more promise, which needs further research.

Objective: To investigate the efficacy and adverse effects of sustained lung inflation (SLI) combined with pulmonary surfactant (PS) in the treatment of neonatal respiratory distress syndrome (NRDS). Methods: This prospective randomized controlled trial included 124 premature infants (gestational age <34 weeks and birth weight <2 000 g) diagnosed with NRDS and in need of PS treatment in Shenzhen Maternity & Child Healthcare Hospital affiliated to Southern Medical University from July 1, 2016 to October 31, 2018. They were randomly divided into experimental or control group, with 62 cases in each. Infants in the experimental group were treated with SLI using T-piece and intratracheal PS, while those in the control group were given PS only. Blood gas analysis and measurement of fraction of inspiration O₂ (FiO₂) and ratio of partial pressure of oxygen (PO₂) over FiO₂ were performed before and 1 h after PS injection. Results of the treatments and incidence of complications were compared. Paired samples t-test, two independent samples t-test, rank-sum test and Chi-square test were used for statistical analysis. Results: There were 56 participants in the experimental group and 54 in the control group who were eventually analyzed. In the experimental group, the pH value, partial pressure of carbon dioxide (PCO₂), FiO₂ and PO₂/FiO₂ at 1 h after PS injection were all improved compared with those before treatment [pH value: 7.26±0.09 vs 7.19±0.09, t=3.814; PCO₂: (51.5±12.6) vs (59.8±16.3) mmHg (1 mmHg=0.133 kPa), t=2.610; FiO₂: 26.0 (21.0-31.5)% vs 40.5 (38.5-51.5)%, U=392.000; PO₂/FiO₂: (284.6±117.9) vs (173.4±59.7) mmHg, t=6.427; all P<0.05]. The overall decrement of FiO₂ after PS injection in the experimental group was more significant than that in the control group [-10.0 (-15.0 to -5.0)% vs -5.0 (-8.0 to 0.0)%, U=706.500, P<0.001]. The experimental group had a higher rate of extubation within 24 h than the control group [80% (45/56) vs 71% (32/54), χ²=5.830, P=0.016]. However, no significant differences were shown in total mechanical ventilation time, non-invasive/high-flow nasal cannula ventilation time, the ratio of re-intubation within 72 h, or the incidence of air leak, bronchopulmonary dysplasia, periventricular-intraventricular hemorrhage, necrotizing enterocolitis or patent ductus arteriosus between the two groups (all P>0.05). Conclusions SLI combined with PS for NRDS babies can increase the rate of extubation within 24 h and promote the down-regulation of FiO₂ without causing significant complications.

Objective To evaluate the effects of ganglioside GM1 on hypoxic ischemic brain damage (HIBD) in neonatal rats and on the expression of potassium-chloride cotransporter 2 (KCC2) in hippocampus.Methods Seven-day-old Sprague-Dawley (SD) rats (n=72) were randomly divided into a sham group,an HIBD group and a ganglioside GM1 group.Each group was further divided into a 3 d subgroup and a 21 d subgroup according to the different detection index (n=12).Rat HIBD models were prepared according the Rice-Vannucci method.After HIBD,the ganglioside GM1 group was given ganglioside GM1 20 mg/ (kg ·d) by intraperitoneal injection for 3 d continuously.2-,3-,5-triphenyltetrazolium chloride (TTC) was preformed to evaluate the area of cerebral infarction of HIBD in each 3 d subgroup.Spontaneous activity recorder was used to observe the locomotor activity of the rats in the 21 d subgroups.Morris water maze test was conducted for assessment of rats' learning and memory abilities in the 21 d subgroups.Western blot analysis was employed to determine the alterations in KCC2 expression in hippocampus in all the 3 d and 21 d subgroups.Results Compared with the HIBD group (28.6％±5.2％),the ratio of cerebral infarction volume in the ganglioside GM1 group (11.3％±2.4％) was significantly reduced (P＜0.05).Compared with the HIBD group (289.6±61.3),the number of locomotor activities within 2 h in the ganglioside GM1 group (412.1±66.8) was significantly increased (P＜0.05).Compared with the HIBD group,the escape latency was significantly reduced,but the percentage time of target quadrant and the number of crossing the platform were significantly increased in the ganglioside GM1 group (P＜0.05).Three days and 21 days after HIBD,the expression of KCC2 in the ganglioside GM1 group was significantly higher than that in the HIBD group (P＜0.05).Conclusion Ganglioside GM1 may have a significant protective effect on HIBD in neonatal rats,and its mechanism may be related to regulation of the expression of KCC2 in hippocampus.

Objective To evaluate the value of monitoring non-invasive cardiac output parameters in medical treatment of patent ductus arteriosus (PDA) in premature infants.Method Premature infants with PDA diagnosed three days after birth (gestational age:28 ～ 31 weeks or birth weight of 1 000 ～ 1 799 g) admitted to the neonatal intensive care unit (NICU) of our Hospital from February 2016 to August 2016 were enrolled in the study.These premature infants were assigned into treated PDA group (the treatment group) and untreated PDA group (the observation group) based on results of non-invasive cardiac output parameters CI and MD,with aorta CI ≥2.95 L/(min · m2),MD ≥21.50 m/min and pulmonary artery CI ≥4.55 L/(min · m2),MD ≥26.50 m/min as cut-off values.Statistical analysis was carried out using t test,x2 test.The closure rate of arterial duct of two groups and changes in non-invasive cardiac output parameters before and after the closure of arterial duct in the treatment group were compared.Result The overall closure rate of arterial duct was 85.1％ (57/67).The closure rate of arterial duct of the treatment group was 70.8％ (17/24),that of the observation group was 93.0％ (40/43),and the difference had statistical significance (P ＜ 0.05);Comparing the following parameters before and after ductal closure in the treatment group,the difference of pulmonary artery flow time (FT),aorta stroke volume index (SVI) and the integral of the flow profile (Vti) had statistical significance (P ＜ 0.05) [(217.6±19.3) ms vs.(235.8 ±21.4) ms,(22.4±6.0)ml/m2 vs.(25.2 ±7.7)ml/m2,(15.1 ± 4.1) cm vs.(17.2 ±5.3) cm].In the treatment group,after arterial duct was closed,aorta and pulmonary artery CI,MD decreased to some degree,but the difference had no statistical significance (P ＞ 0.05).Conclusion Non-invasive cardiac output parameters including aorta and pulmonary artery CI,MD have certain guiding significance for PDA drug treatment among premature infants;after PDA drug treatment,arterial duct closure condition cannot be judged simply by the changes of aorta and pulmonary artery CI,MD,ultrasonic cardiogram examination results should also be considered.

OBJECTIVETo explore the surgical techniques and feasibility of robotic surgery for carcinoma in the remnant stomach(CRS).

METHODSClinicopathological data of 20 CRS patients undergoing robotic surgery at the Minimally Invasive Center for Gastrointestinal Surgery, Army Medical University Southwest Hospital from November 2012 to October 2017 were retrospectively collected. The surgical methods, procedures, main difficulties, and key techniques were analyzed, and the clinical efficacy was evaluated.

RESULTSAmong 20 CRS patients, 14 were male and 6 were female with mean age of 59.9 years and mean BMI of 19.7 kg/m. For the primary diseases, 17 patients underwent laparotomy, 3 underwent laparoscopic radical resection of gastric cancer; 18 cases received distal subtotal gastrectomy plus Billroth II( anastomosis, 2 received distal subtotal gastrectomy plus Billroth I( anastomosis. CRS located in anastomotic stoma in 15 cases and in the gastric fundus and cardiac part in 5 cases. Preoperative staging revealed 2 cases of T2NxM0, 1 of T3NxM0, 2 of TxNxM0 and 15 of T4aNxM0. Sixteen patients received robotic surgery with Roux-en-Y reconstruction successfully, and 4 patients were converted to laparotomy for palliative total gastrectomy, including 1 case with diaphragm invasion, 1 case with transverse colon invasion, and 2 cases with tight adhesions. The mean surgery time was (255±35) minutes, mean blood loss was (230±50) ml, mean number of dissected lymph nodes was 19.5±3.0, mean recovery time to gastrointestinal function was (2.3±1.0) days, mean time to feeding was (2.3±1.0) days, and mean time to ambulatory activity was (2.5±0.5) days. Pathological examinations revealed 12 patients with poorly differentiated adenocarcinoma, 6 patients with moderately differentiated adenocarcinoma, and 2 patients with mucinous adenocarcinoma. Postoperative pTNM staging was identified as follows: stage I(B for 1 patient, stage II(A for 2 patients, stage II(B for 5 patients, stage III(A for 5 patients, stage III(B for 4 patients, and stage III(C for 3 patients. One patient died 2 weeks after operation due to multiple organ failure. One patient received another hemostasis operation due to hemorrhage of splenic artery and recovered postoperatively. Two patients experienced anastomotic leakage, 1 patient developed duodenal stump fistula and 1 patient experienced incision site infection postoperatively, and all of them recovered after conservative treatment. During 5-60 months follow-up, 10 cases died and 10 cases survived, including 1 case for 6 years.

CONCLUSIONSRobotic surgery for CRS is feasible with satisfactory short-term efficacy. However, the long-term efficacy requires further study.

Female ; Gastrectomy ; Gastric Stump ; surgery ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Robotic Surgical Procedures ; Stomach Neoplasms ; surgery

Objective To investigate the post-mortem brain histopathology in patients with systemic lupus erythematosus (SLE).Methods The medical records and cerebral autopsy tissue of nine patients with SLE autopsied during 1956--2000 in Peking Union Medical College Hospital were collected and reviewed.Results Nine patients were all female and the average age was (29±11) years.Eight out of nine patients clinically presented with neurological manifestations.Brain histopathology changes were identified as follow:brain parenchyma change was shown in eight cases (8/9),cerebral hernia in six cases (6/9),cerebral hemorrhage in four cases (4/9),infarction in three cases (3/9),ventricular dilation in three cases (3/9),meningitis in two cases (2/9) and vasculopathy in one case (1/9).Vasculitis was not shown in any patients.Conclusion The brain histopathology in SLE includes vasculopathy,infarction,hemorrhage,infection,meningitis,ventricular dilation,cerebral hernia,brain parenchyma change,etc.Among the above changes,brain parenchyma changes,cerebral hernia and hemorrhage are the most commonly shown,while vasculitis is uncommonly presented.SLE patients with brain histopathology changes may even without clinically manifestation.All patients with SLE should be alert to neurological involvement.

Objective To investigate the preventive and adverse effects of postnatal inhalation of Budesonide in early stage on bronchopulmonary dysplasia (BPD) in very low birth weight infants.Methods A total of 105 cases of high risk premature infants with BPD,who were born in the Neonatal Intensive Care Unit (NICU) from Shenzhen Maternity and Child Healthcare Hospital from July 15,2015 to December 25,2016,and their gestational age ≥ 27 weeks and ＜ 32 weeks or birth weight ≥ 1 000 g and ＜ 1 500 g were collected for a prospective randomized controlled trial,and were randomly divided into 3 groups:early inhalation group(34 cases),late inhalation group(34 cases) and non-inhalation group(37 cases).The oxygen time,and the incidence of BPD,periventricular-intraventricular hemorrhage (IVH),retinopathy of prematurity (ROP),necrotizing enterocolitis of the newborns (NEC),patent ductus arteriosus in preterm infants (PDA),sepsis and hyperglycemia of infants in 3 groups were compared.Results The average oxygen time in early inhalation group was 9 days,while in late inhalation group and the non-inhalation group was 15 days and 18 days,respectively.The average oxygen time in early inhalation group was significantly lower than that in the late inhalation group and the non-inhalation group,with the difference being statistically significant (H =6.09,P ＜ 0.05).The noninvasive ventilation time in early inhalation group was 3 days,while both the late inhalation group and non-inhalation group were 6 days.The noninvasive ventilation time in early inhalation group was significantly lower than that in the late inhalation group and non-inhalation group,with the difference being statistically significant (H =6.17,P ＜0.05).The incidence of BPD in the early inhalation group,late inhalation group and non-inhalation group were 14.7％ (5/34 cases),20.6％ (7/34 cases) and 37.8％ (14/37 cases),respectively.The incidence of BPD in non-inhalation group was significantly higher than that in the early inhalation group and late inhalation group,with the difference being statistically significant (x2 =12.017,P ＜ 0.05).There were no significant differences in IVH,ROP,NEC,PDA,sepsis and hyperglycemia among the 3 groups (all P ＞ 0.05).Conclusions Postnatal inhalation of Budesonide in early stage in high risk very low birth weight infants can reduce the incidence of BPD and the oxygen time,and the adverse reactions are not obvious.