OBJECTIVE To elucidate the mechanisms responsible for the inhibitory effects of limonene on the proliferation of non-small cell lung cancer(NSCLC) by non-targeted metabolomics and additional approaches. METHODS The CCK-8 assay was utilized to evaluate the inhibitory effects of limonene on NSCLC A549 cell viability and to ascertain the IC50. In vitro experiments, encompassing colony formation, flow cytometry, iron content assessment, and mitochondrial staining, were conducted to assess the anti-lung cancer and iron-induced cell death effects of limonene. Metabolomic analysis was employed to identify potential pathways influenced by limonene, and Western blotting was carried out to validate pivotal proteins within these pathways. RESULTS In comparison to the control group, the limonene-treated group demonstrated a significant, dose-dependent reduction in A549 cell proliferation and colony formation. Optical microscopy revealed cellular detachment and pronounced changes in cellular morphology following exposure to limonene. Limonene induced apoptosis in A549 cells and arrested them in the G0-G1 phase of the cell cycle. Confocal microscopy unveiled diminished mitochondrial fluorescence and an augmented intracellular iron content, indicative of the classical phenomenon of ferroptosis. Metabolomic investigations unveiled divergent metabolic pathways, including glutathione(GSH) metabolism, arginine biosynthesis, D-glutamine and D-glutamate metabolism, as well as cysteine and methionine metabolism, with many of them intricately linked to intracellular GSH synthesis. Western blotting experiments underscored a marked reduction in the levels of SLC40A1, SLC7A11(xCT), and GPX4 proteins within the cells post-limonene treatment. CONCLUSION Limonene may induce ferroptosis in lung cancer cells by reducing GSH synthesis and increasing Fe2+ levels.

Objective:To identify the dosimetric and radiobiological differences of three radiotherapy techniques of whole breast irradiation with simultaneous integrated boost (WBI-SIB) following breast-conserving surgery for early breast cancer (EBC).Methods:The data of 20 patients with early left-sided breast cancer who received radiotherapy following breast-conserving surgery were retrospectively analyzed. Three radiotherapy techniques, namely hybrid intensity-modulated radiotherapy (HIMRT), intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), were redesigned with the same prescription dose and target conditions. Then, doses to target volume (TV) and organs at risk (OAR), along with the normal tissue complication probability (NTCP) and secondary cancer risk (SCR) for specific organs, were compared.Results:Compared to HIMRT and IMRT, VMAT led to significant decreases in various dosimetric indices of the affected lung and heart and increases in the Dmean doses to the healthy lung and healthy breast and V5 Gy doses to the healthy breast, with the differences being significantly different ( P < 0.05). The average NTCP values of cardiac death, radiation pneumonitis, and pulmonary fibrosis induced by VMAT were 0.41%, 1.62%, and 23.59%, respectively, significantly lower than those caused by other two techniques ( P < 0.05). No statistical differences were found in 10 dosimetric indices of OAR between IMRT and HIMRT, while the NTCP analysis suggested that the risks of cardiac death ( t = 2.70, P < 0.05) and pulmonary fibrosis ( t =4.11, P < 0.05) induced by IMRT were slightly lower than those caused by HIMRT. In addition, the excess absolute risk (EAR) to the healthy lung posed by VMAT was 1.65 and 1.83 times those induced by HIMRT and IMRT, respectively ( z = -3.92, t = -6.43, P < 0.05). In contrast, the EAR to the healthy breast induced by VMAT was 2.79 and 2.65 times those posed by HIMRT and IMRT, respectively ( z = -3.21, -3.70, P < 0.05). Conclusions:Among three intensive-modulated radiotherapy techniques of WBI-SIB for EBC, VMAT provides the optimal protection for the heart and affected lung but leads to the highest SCR to the healthy lung and breast. When VMAT is employed for young EBC patients or those with normal cardiopulmonary function, special attention should be paid to reducing low-dose irradiations to the healthy breast and thereby minimizing SCR. In contrast, VMAT might be more favorable for patients with pronounced cardiopulmonary risks or aged patients.

Objective:To investigate the effects of intra-articular injection of exosomes derived from dental pulp stem cells from hu-man exfoliated deciduous teeth(SHED-EXO)on subchondral bone homeostasis in rat temporomandibular joint osteoarthritis(TMJ OA)process.Methods:36 male SD rats were randomly divided into 3 groups(n=12):control(CON),sodium iodoacetate(MIA)-induced TMJ OA(MIA),and SHED-EXO injection into TMJ OA(SHED-EXO)groups.At 2 and 6 weeks post-treatment,Micro-CT,Double labeling,TRAP staining,and immunohistochemical staining were employed to detect osteoclasts and osteoblasts in the subchondral bone.Additionally,the mRNA expression levels of ADAMTs5,IL-1β,OCN and OPG/RANKL were analyzed by qRT-PCR.Results:The MIA group exhibited significant bone loss and an enlarged bone marrow cavity.In comparison with the CON group,BV/TV and Tb.Th were lower(P＜0.001),while BS/BV,Tb.Sp,and Tb.N were higher(P＜0.01).Additionally,the bone formation rate within 5 days was low-er than that of the control group(P＜0.001).When compared to the MIA group,the SHED-EXO group showed a significant increase in bone morphology and bone mass.BV/TV and Tb.Th were increased(P＜0.01),while BS/BV,Tb.Sp and Tb.N were decreased(P＜0.05).The bone formation rate was higher(P＜0.01).Compared with both the control and treatment groups,the MIA group exhibited a significant increase in the number of osteoclasts in the subchondral bone(P＜0.01),along with a notable decrease in H-type blood vessels and OCN-positive areas(P＜0.01).Conclusion:Intra-articular injection of SHED-EXO can reg-ulate condylar subchondral bone homeostasis in TMJ OA of rats by promoting osteogenesis and inhibiting osteoclasts.

30 patients with chronic periodontitis and Type 2 diabetes mellituse were included.By a split-mouth design,the teeth in the left side were served as the experiment group and given Nd∶YAG and Er∶YAG laser therapy adjunctive to conventional periodontal treatment;the teeth in the right side were served as the control group and given conventional periodontal treatment alone.Before and after treatment perio-dontal and CBCT image indexes were examinde and compare between the 2 groups.Before treatment all the indexes were not statistically dif-ferent between the 2 groups(P＞0.05).3 months after treatment,the bleeding index(BI)and probing depth(PD)of the experimental group were significantly lower than those of the control group(P＜0.05).6 months after treatment,BI,PD and attachment loss(AL)in the experi-mental group were significantly lower than those in the control group,and the surface area and volume of the root in the alveolar bone were significantly higher than those in the control group(P＜0.05).Nd∶YAG and Er∶YAG laser therapy adjunctive to conventional periodontal treatment is more effective than conventional periodontal treatment alone in the treatment of chronic periodontitis with type 2 diabetes melli-tus.

Objective:To explore the effects of teaching with standardized patients and trauma simulators in surgical debridement training.Methods:Forty-two undergraduate medical students were randomly divided into research group ( n=21) and control group ( n=21) during surgical debridement training in clinical skills simulation training courses. The research group received training using standardized patients combined with trauma simulators, while the control group received training using the simulated teaching method. After training, an examination test and a questionnaire survey were conducted to investigate whether the teaching method under study improved students' doctor-patient communication skills, humanistic care skills, and clinical operational skills. SPSS 20.0 was used to perform the t test and chi-square test. Results:The research group had significantly higher scores in debridement procedures [(65.63±2.58) vs. (62.92±3.88)], communication [(18.62±0.67) vs. (12.71±1.89)], and humanistic care [(8.52±0.51) vs. (6.33±1.11)] than the control group (all P<0.05). The survey results showed that medical students were more satisfied with the teaching method with standardized patients and trauma simulators, believing that it could improve doctor-patient communication skills, humanistic care skills, and clinical practice levels ( P<0.05). Conclusion:The teaching method with standardized patients and trauma simulators can improve training effects, which is worth promotion.

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

Objective:To observe the effect of well-designed board sanding training on the upper extremity motor functioning of hemiplegic stroke survivors.Methods:Sixty stroke survivors with hemiplegia were randomly divided into an observation group (30 cases) and a control group (30 cases). All received conventional rehabilitation. The observation group′s training involved intelligent board sanding, while the control group′s training involved traditional sanding.Results:After the treatment, significant improvement was observed in the Fugl-Meyer upper extremity scores, modified Barthel index scores and reported shoulder pain in both groups, with the observation group′s averages significantly better than those of the control group. After the intervention, the average scores of both groups on the modified Ashforth scale had also improved significantly.Conclusions:Supplementing conventional rehabilitation treatment with intelligent board sanding can significantly improve upper extremity motor function and ability in the activities of daily living of stroke survivors with hemiplegia while somewhat relieving shoulder pain. The effect is better than with traditional board sanding.

Objective:To summarize the clinical characteristics, common images, pathogens, and gene mutation types of chronic granulomatosis disease (CGD) in 19 children.Methods:The clinical manifestations, laboratory findings, treatment, and prognosis of 19 patients diagnosed with CGD in Hong Kong University-Shenzhen Hospital from December 2012 to December 2018 were analyzed.Results:The 19 patients were all males and confirmed as CGD by the dihydrorhodamine test and gene sequencing.The age of the first infection was mostly 1 month after birth(13 cases), and the age of clinical diagnosis ranged from 2 months to 10 years.Sixteen mothers were carriers.The patients presented with pulmonary fungal infection (19/19 cases), Bacillus Calmette Guerin (BCG)-osis (14/19 cases), lymphadenitis (14/19 cases), perianal abscess (9/19 cases), skin abscess (5/19 cases) and ulcerative colitis (2/19 cases). There were 59 positive cultures.Pathogens included fungi (9 cases), Klebsiella pneumonia (8 cases), mycobacteria (7 cases), Streptococcus Viridans (5 cases), Escherichia coli (3 cases), gram-positive bacteria (3 cases), Staphylococcus aureus (3 cases), and Burkholderia cenocepacia (2 cases). Gene mutations were found in all 19 patients, including 17 cases of CYBB, 1 case of CYBA and 1 case of NCF2.The type of mutations included nonsense mutations (6 cases), deletion mutations (5 cases, including 2 large fragment deletions), splice mutations (3 cases) and missense mutations (5 cases). Five mutations were novel.Splice mutations in 3 cases often led to skin abscess, perianal abscess and lymphadenitis.Two patients with large deletion mutations had more serious infection than other patients. Conclusions:In China, CGD is characterized with pulmonary infection and disseminated BCG-osis.Mycobacteria are common pathogens of CGD, and fungi are dominant pathogens of CGD.The most common infection is respiratory infection. Klebsiella pneumonia and Escherichia coli often lead to perianal abscess.The relationship between gene mutation types and clinical phenotypes requires further verification by big data.

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.
Acute Disease ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Appendectomy ; Appendicitis ; diagnosis ; therapy ; China ; Female ; Health Care Surveys ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Objective: To explore the clinical efficacy and safety of injecting lobaplatin through hepatic artery puncture combined with percutaneous catheter selective portal vein embolization(SPVCE) in the treatment of primary liver cancer. Methods: A total of 118 patients with advanced primary liver cancer admitted to Binzhou Central Hospital of Shandong Province from August 2015 to January 2017 were selected as in the study, and randomly divided into two groups according to the digital table, namely TACE(hepatic carcinoma arterial perfusion chemoembolization)+ SPVCE group and TACE group, with 59 cases in each group.In the TACE+ SPVCE group, injection lobaplatin was administered with gelatin sponge as the drug-borne embolic agent, superselective hepatic artery chemoembolization(TACE) combined with SPVCE was performed, regional embolization was performed for liver cancer, and only TACE was administered in the TACE group.The curative effect and adverse reactions of the two groups were observed and compared. Results: The short-term objective(CR+ PR) efficiency of the TACE+ SPVCE group was 74.57%(44/59), which was significantly higher than that of the TACE group [54.23% (32/59)], the difference was statistically significant(χ²=5.323, P=0.021). The differences were statistically significant in the main indicators, such as the decrease of tumor lesion volume, the increase of liver volume without cancer, and the decrease of FAP(all P<0.05). The long-term objective efficiency of the TACE+ SPVCE group was 45.76%(27/59), which was also significantly higher than that of the TACE group[32.2%(19/59)], but the difference was no statistically significant(χ²=2.280, P=0.131). The TACE+ SPVCE group extended the median survival time by 3.5 months compared to the TACE group, there was statistically significant difference in median survival between the two groups(t=3.211, P=0.000). Major adverse reactions were compared between the two groups, the patients with decreased albumin in the TACE + SPVCE group was less than the TACE group, but there was no statistically significant difference(χ²=1.156, P=0.282), the patients with bone marrow inhibition in the TACE + SPVCE group decreased significantly compared with the TACE group, the difference was statistically significant(χ²=4.882, P=0.027), patients with severe gastrointestinal tract decreased compared with conventional TACE group, but there was no statistically significant difference(χ²=1.035, P=0.308). Conclusion Injection for drug carrier with lobaplatin with gelatin sponge embolism agent, percutaneous puncture catheter super choice hepatic artery hepatic artery embolism chemotherapy combined with percutaneous puncture catheter SPVCE for primary liver cancer lines of regional embolization, is safe and effective, and can improve the curative effect of conventional TACE, and prolong survival, has important clinical value for advanced liver cancer patients that cannot be surgically removed.