BACKGROUND: Neoadjuvant therapy enhances the possibility of achieving radical resection and improves the prognosis for locally advanced gastric cancer (GC). However, there is a lack of evidence regarding the optimal extent of resection for locally advanced proximal GC after neoadjuvant therapy. METHODS: In this study, 330 patients underwent resection in Peking University Cancer Hospital, with curative intent after neoadjuvant therapy for histologically confirmed proximal GC from January 2009 to December 2022. RESULTS: In this study, 45 patients underwent proximal gastrectomy (PG), while 285 underwent total gastrectomy (TG). After propensity-score matching, 110 patients (71 TG and 39 PG) were included in the analysis. No significant differences between PG and TG regarding short-term outcomes and long-term prognosis were found. Specifically, PG demonstrated comparable overall survival to TG ( P = 0.47). Subgroup analysis revealed that although not statistically significant, PG showed a potential advantage over TG in overall survival for patients with tumor-long diameters less than 4 cm ( P  = 0.31). However, for those with a long diameter larger than 4 cm, TG had a better survival probability ( P  = 0.81). No substantial differences were observed in baseline characteristics, surgical safety, postoperative recovery, and postoperative complications. CONCLUSION For locally advanced proximal GC with objective response to neoadjuvant therapy (long diameter <4 cm), PG is an alternative surgical procedure.
Humans ; Stomach Neoplasms/drug therapy* ; Gastrectomy/methods* ; Neoadjuvant Therapy/methods* ; Male ; Female ; Middle Aged ; Propensity Score ; Aged ; Adult ; Retrospective Studies

Objective To investigate the protective effect of PF-562271,a FAK inhibitor,against aging platelet-induced injury in human umbilical vein endothelial cells(HUVECs).Methods Cultured HUVECs were treated with vehicle,lipopolysaccharide(LPS),LPS+aging platelets,or LPS+aging platelets+PF-562271.The changes in protein expressions of FAK,pFAK and PECAM-1 in the treated cells were detected using Western blotting and immunofluorescence assay,and the level of reactive oxygen species(ROS)was detected with flow cytometry.The changes of barrier function of the cells were assessed with cell permeability test and transendothelial cell resistance test.RT-qPCR was used to analyze mRNA expressions of inflammatory factors,and pro-inflammatory cytokine levels in the culture supernatants was determined with enzyme-linked immunosorbent assay.Immunofluorescence assay was used to examine the effect of the ROS inhibitor vitamin C on PECAM-1 expression in the cells with different treatments.Results Treatment of HUVECs with LPS and aging platelets significantly increased cellular protein expressions of FAK,pFAK and PECAM-1,which were effectively lowered by addition of PF-562271(P<0.05).LPS and aged platelets obviously enhanced ROS production in the cells,which was inhibited by the addition of PF-562271(P<0.001).PF-562271 significantly alleviated the damage of endothelial cell barrier function of the cells caused by LPS and aging platelets(P<0.01).The expressions of TNF-α,IL-6 and IL-8 in HUVECs increased significantly after exposure to LPS and aging platelets,and were obviously lowered after treatment with PF-562271(P<0.05).Treatment with vitamin C significantly decreased the expression of PECAM-1 protein in the cells(P<0.01).Conclusion The FAK inhibitor PF-562271 alleviates endothelial cell damage induced by LPS and aging platelets by lowering cellular oxidative stress levels and reducing inflammatory responses.

Objective To investigate the protective effect of PF-562271,a FAK inhibitor,against aging platelet-induced injury in human umbilical vein endothelial cells(HUVECs).Methods Cultured HUVECs were treated with vehicle,lipopolysaccharide(LPS),LPS+aging platelets,or LPS+aging platelets+PF-562271.The changes in protein expressions of FAK,pFAK and PECAM-1 in the treated cells were detected using Western blotting and immunofluorescence assay,and the level of reactive oxygen species(ROS)was detected with flow cytometry.The changes of barrier function of the cells were assessed with cell permeability test and transendothelial cell resistance test.RT-qPCR was used to analyze mRNA expressions of inflammatory factors,and pro-inflammatory cytokine levels in the culture supernatants was determined with enzyme-linked immunosorbent assay.Immunofluorescence assay was used to examine the effect of the ROS inhibitor vitamin C on PECAM-1 expression in the cells with different treatments.Results Treatment of HUVECs with LPS and aging platelets significantly increased cellular protein expressions of FAK,pFAK and PECAM-1,which were effectively lowered by addition of PF-562271(P<0.05).LPS and aged platelets obviously enhanced ROS production in the cells,which was inhibited by the addition of PF-562271(P<0.001).PF-562271 significantly alleviated the damage of endothelial cell barrier function of the cells caused by LPS and aging platelets(P<0.01).The expressions of TNF-α,IL-6 and IL-8 in HUVECs increased significantly after exposure to LPS and aging platelets,and were obviously lowered after treatment with PF-562271(P<0.05).Treatment with vitamin C significantly decreased the expression of PECAM-1 protein in the cells(P<0.01).Conclusion The FAK inhibitor PF-562271 alleviates endothelial cell damage induced by LPS and aging platelets by lowering cellular oxidative stress levels and reducing inflammatory responses.

Objective:To evaluate the efficacy of dexmedetomidine for patient-controlled sleep regulation in improving postoperative sleep disorders in patients with gastrointestinal tumors.Methods:One hundred and fifty American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, regardless of gender, aged 40-80 yr, with a preoperative Pittsburgh Sleep Quality Index (PSQI) score of ≤7 and a PSQI score of >7 on the 1st day after surgery, undergoing elective laparoscopic resection of gastrointestinal tumors from May 2023 to December 2023 in the Affiliated Changzhou No. 2 People′s Hospital of Nanjing Medical University, were divided into 3 groups ( n=50 each) using a random number table method: normal saline group and dexmedetomidine via different routes of administration groups (DEX1 group, DEX2 group). After the routine use of 48 h postoperative analgesia, dexmedetomidine 400 μg and atropine 1 mg in 100 ml of normal saline were added to the analgesic pump in DEX1 and DEX2 groups, DEX1 group received a background infusion at a rate of 2.5 ml/h, and after an initial dose of 6 ml, the patient-controlled analgesia (PCA) pump was programmed to deliver 4 ml with a lockout interval of 10 min and background infusion at 0.5 ml/h in DEX2 group. In NS group, normal saline was added to the PCA pump, and the methed of petient-controlled administration was the same as those previously described in DEX2 group. PSQI scores were recorded at days 1, 3 and 7 and 1 month postoperatively, and visual analogue scale scores were recorded on postoperative days 1, 3 and 7. Personal Health Questionnaire Depression Scale scores were assessed and the polysomnogram was monitored on the preoperative day 1, and 15-item Quality of Recovery (QoR-15) scale scores were assessed on postoperative day 7. The duration of PACU stay, consumption of anesthetic drugs, the total pressing times of PCA within 48 h, consumption of analgesic drugs and lenth of hospital stay were recorded. Results:Compared with NS group, the sleep stage N1 ratio and arousal index were significantly decreased and the sleep stage N2 ratio and sleep efficiency were increased on postoperative days 3 and 7, PSQI scores at days 3 and 7 and 1 month after operation and VAS score at postoperative day 7 were decreased, the length of hospital stay was shortened in DEX1 and DEX2 groups, and QoR-15 scale scores were significantly increased in DEX2 group ( P<0.05). Compared with DEX1 group, the sleep stage N3 ratio was significantly increased, PSQI scores were decreased on postoperative days 3 and 7, and QoR-15 scale scores were increased in DEX2 group ( P<0.05). Multivariate logistic regression analysis showed that dexmedetomidine for patient-controlled sleep regulation was a protective factor against postoperative sleep disturbances ( P<0.05). Conclusions:For the patients with postoperative sleep disorders following surgery for gastrointestinal tumors, self-controlled administration of dexmedetomidine for 3 consecutive days after surgery improves the sleep structure, raises the subjective sleep quality and promotes the postoperative recovery.

Objective:To observe the effects of ointment and massage on inflammation, oxidative stress and angiogenesis after skeletal muscle trauma, and to explore their mechanisms.Methods:Forty-two adult male Sprague-Dawley rats were randomly divided into a blank group ( n=6), an ointment and massage (O&M) group ( n=18) and a model group ( n=18). The blunt contusion model of gastrocnemius malformation was established in both the O&M and model groups using self-made percussion instruments. Two hours after successful modeling, the anti-inflammatory pain-relieving cream was applied to the injured area, and massaged evenly and gently for 5 minutes. That was repeated with an interval of 12 hours. No treatment was given to the model and blank groups. On the 1st, 3rd and 7th days after modeling, injured gastrocnemius muscles were resected after collecting abdominal blood. Hematoxylin-eosin (HE) staining and immunofluorescent (CD34) staining were applied, and serum superoxide dismutase (SOD) and malondialdehyde (MDA) contents were detected. Results:HE staining showed that at each time point the gastrocnemius muscle fibers of the model group were significantly more swollen and deformed, collapsed and dissolved than those of the blank group, with a large number of inflamed cells. The O&M group had better recovery, with more newly-generated muscle cells, less inflammatory infiltration and more normal cell shapes than the model group. Fluorescence was stronger in the O&M and model groups than in the blank group at each time point, with that of the O&M group significantly stronger than in the model group. The average SOD and MDA levels in the model and O&M groups were significantly higher than in the blank group, and on the 1st and 3rd days the O&M group′s average SOD level was significantly higher than the model group′s average, though by the 7th day there was no significant difference. The average MDA content of the O&M group was significantly lower than the model group′s average at each time point.Conclusion:Ointment and massage can effectively reduce the local inflammatory response and oxidative stress after a skeletal muscle injury. They can accelerate local angiogenesis, promoting the repair of damaged tissues.

As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.

Objective:To understand the current situation about pre-registered medical practitioner's ineligible practice from a legal point of view and provides references forthe Law of Medical Practitioners.Methods:The sur-vey is based on cluster sampling method which centralized the selected large clinical teaching hospitals which have launched the standardized residents training.The research is focused in Beijing and involves three kinds of people in-cluding the pre-registered medical practitioners, clinical teaching teachers and health administrators.The descriptive statistics and the Comparison rates between groups by chi-square test rates were adopted.Meanwhile, the 764 medi-cal malpractice cases from the past three years were analyzed in the Courts of the People of Haidian and the Beijing Chaoyang Districts.Results:The clinical trainees“pre-registration” made illegal situations such as independent vis-its, finding a single worker on duty, independent patient disposal, invasive technology's independent operation, inde-pendently writing the medical records, and the absence of tutors on the supervision sites.All of these mischiefs en-hanced the occurrence of medical disputes.Suggestions: Based on the current situation, it is necessary to establish the legal qualifications for the“pre-registered” trainees engaged in the accredited clinical work legislation, physician qualification examination, and in so many angles.Proposing solutions based on legal issues about “the practitioner guidance” should also be efficient.

Objective To evaluate the effect of the hyperbaric oxygenation therapy on the apoptosis of the hippocampal neuron and the impairment of cognitive function of the newborn rats suffering from bilirubin encephalopathy. Methods One hundred and forty-five five-day-old SD rats of both sex were randomly divided into 3 groups,control group,bilirubin encephalopathy group and hyperbaric oxygenation treated group. Bilirubin ( 10 mg/ml) was injected into the cerebellomedullary cistern to establish experiment model,and normal sodium was injected for control. The expression of cytochrome C and Caspase-3 in the hippocampus neurons were detected by immunohistochemistry and immunofluorescence,respectively,at the time of 6 h,1,3,5 d and 7 d after intra-cisternal injection. Neuronal apoptosis was checked by TUNEL method. The cognitive function was tested by Morris experiment. Results The expressions of the cytochrome C and Caspase-3 in hyperbaric oxygenation treated group were lower than those in bilirubin encephalopathy group,but higher than control group at abovementioned time points ( P

A reference system for the completed blood count (CBC) have been established in National Center for Clinical Laboratory (NCCL) according to the standards published by International Council for Standardization in Hematology (ICSH) and International Organization for Standardization (ISO) in order to calibrate hematology analyzer.The contents of our study mainly include:(1)Establishment of calibration laboratory for CBC, which is the first calibration laboratory accepted by China National Accreditation Board for Laboratories in all medical laboratories.(2)We firstly set up the reference method for CBC in China. In addition, the data between NCCL and a foreign reference laboratory have been compared. (3)We have calibrated some instruments from routine laboratories by the fresh blood or calibrator valuated by the reference system, which acts as a new way to calibrate hematology analyzer.(4) A secondary standard assay system has been established and the data between it and the foreign reference laboratory have been compared chronically. The experience has been introduced to local laboratories in 26 provinces.(5) We have drafted out several documents about technical standard for laboratory medicine. The main institution of applications includes: local center for clinical laboratory, clinical laboratories for routine examination, institutions for identification to instruments and reagents, centers for disease control and prevention, and so on.