ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

ObjectiveTo explore the clinical characteristics and risk factors for 30-day mortality in hospitalized patients with bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MethodsData were obtained retrospectively from the electronic medical records of inpatients at a tertiary A-grade hospital in Shanghai from January 2016 to December 2023. The collected variables included age, gender, department, surgical treatment, empirical antibiotic therapy, Pitt Bacteremia score (PBS), Charlson comorbidity index (CCI), INCREMENT-CPE score (ICS), length of hospital stay, the time from CRKP-BSI to discharge and, etc. The follow-up period ended upon discharge, with the follow-up outcomes defined as in-hospital mortality or discharge. The endpoint was defined as death within 30 days (including day 30) caused by CRKP-BSI or infection-related complications. Patients who survived within 30 days after CRKP-BSI were classified into the survival group, while those who died within 30 days were classified into the death group. Independent risk factors for 30-day mortality in patients with CRKP-BSI were analyzed using univariate and multivariate Cox regression analysis. ResultsA total of 71 hospitalized patients with CRKP-BSI, comprising 51 males and 20 females, with an average age of (65.12±18.25) years, were included during the study period. The M (P₂₅, P₇₅) of hospital stay were 37.00 (24.00, 56.00) days, and M (P₂₅, P₇₅) of the duration from CRKP-BSI to discharge or death were 18.00 (7.00, 35.00) days. There were 20 deaths (28.17%) in the death group and 51 survivors (71.83%) in the survival group. The results of multivariate Cox regression analysis showed that the ICS as an independent risk factor for 30-day mortality in CRKP-BSI patients (HR=1.379, 95%CI: 1.137‒1.671, P=0.001). Each 1-point increase in the ICS was associated with a 37.9% increase in the risk of mortality. ConclusionThe ICS is found to be a risk factor for 30-day mortality in patients with CRKP-BSI, which may facilitate the prediction for the risk of 30-day mortality and thereby support clinical decision-making for patients with CRKP-BSI.

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Objective:To explore the characteristics and data related to the degradation and biocompatibility of the domestically procuded polyglycolic acid (PGA) nerve conduit.Methods:This study was conducted in the Department of Burns and Plastic Surgery, the Northern Theater General Hospital between January and August 2022. PGA nerve conduits were immersed in 15 ml normal saline for in vitro experiments of degradation. The experimental period was 12 weeks. The pH of the immersion solution were tested weekly and the rates of mass loss were calculated. The in vitro experiments for biocompatibility were conducted in both of the experimental group and the control group. In the experimental group, a DMEM solution containing 10% of fetal bovine serum was used as the extraction medium, and domestically produced PGA nerve conduit was immersed in the extraction medium in the control group. An extraction medium was firstly prepared for a controlled extraction time of 72 hours±2 hours at 37 ℃±1 ℃. The pH of both experimental and control groups were tested at 24, 48 and 72 hours. The 72-hour extracts of both experimental and control groups were used to prepare the single cell suspension. The single cell suspension containing the cultured RSC 96 were separately seeded into 96-well plates for Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, to observe the effect of PGA nerve conduits on the proliferation of RSC 96. Then RSC 96 were incubated for 24 hours with the extracts of both experimental and control groups. The effect of PGA nerve conduits on the migration of RSC 96 was observed with Transwell assay. Twenty-four adult male SD rats were used and divided into experimental group and control group, with 12 rats per group, for the in vivo study of degradation and biocompatibility. Rats in the experimental group were implanted with domestically produced PGA nerve conduits, and Neurotubes, a US made nerve conduit, were implanted in the rats of control group. The PGA nerve conduits were implanted in a bluntly prepared gap between the biceps femoris muscle and the gluteus maximus muscle of the right hind limb of rats for the in vivo degradative experient. The degradation and biocompatibility of the PGA nerve conduit were evaluated by means of gross observation, tests of blood routine, liver and kidney functions and histological examinations at 2, 4, 8 and 12 weeks after implantation. SPSS 19.0 software was used for statistical analysis of the experimental data, and the results were expressed as Mean±SD. T test was used for inter-group comparison and Turkey method was used for intra-group and inter-group comparison. P<0.05 was used to determine whether the difference was statistically significant. Results:The rate of in vitro degradation was found at 1.470%±0.026% in week 4, and thereafter, a gradually accelerated degradation rate was observed and at a 32.180%±0.040% of degradation rate in week 12. The pH of the immersion solution decreased slowly in the first 2 weeks, with the pH at 6.200±0.061 in week 2. The pH then suddenly dropped to 3.930±0.118 in week 3, and then decreased slowly, with a pH 2.560±0.003 in week 12. Both MTT and Transwell experiments showed that the extract of PGA nerve conduits had no effect on the proliferation and migration of RSC 96, nor a significant difference existed in comparison with the corresponding control groups ( P>0.05). The experiments of in vivo degradation of PGA nerve conduits showed that the nerve conduits in both experimental and control groups had good support at week 2 after implantation. At weeks 4-12 after implantation, the nerve conduits in both groups gradually softened and collapsed, but the conduits were in one piece and not broken. The blood routine, liver and kidney functions showed no statistically significant difference between the 2 groups over the same period, and between each time point within the groups and the groups before implantation ( P>0.05). No obvious abnormal appearance of livers and kidneys was found in the rats sacrificed at each observation time point. Also, there was no obvious degeneration and necrosis of the muscle tissue around the conduits in the 2 groups, and no obvious inflammatory cells infiltration was found from the histological examinations. Morphology of the muscle tissue remained normal. Conclusion:Domestically produced PGA nerve conduit is fund good in both of biocompatibility and biodegradability. It is safe and reliable, and it provides a basis for the further experients in repair of nerve defects.

Objectives:To identify the risk factors associated with delirium in intensive care unit (ICU) hospitalization of sepsis patients and construct a clinical prediction model to to provide a reference for the prevention and control of delirium in sepsis patients.Methods:Data were collected of sepsis patients admitted in the Intensive Care Unit in the Second Affiliated Hospital of Soochow University from September 2020 to August 2022.The patients were divided into delirium group and non-delirium group according to whether delirium occurred or not. Comparing of the differences in general and clinical data between the two groups, the independent risk factors for delirium were screened by backward stepwise regression method, and the delirium risk prediction model was constructed and evaluated. An independent risk factor analysis for delirium was conducted using a backward stepwise regression approach to identify significant predictors. A delirium risk prediction model was constructed based on the identified risk factors, followed by a comprehensive evaluation of the model's performance.Results:A total of 381 sepsis patients were included in the study, 114 patients (29.9%) developed delirium during the ICU hospitalization. Univariate analysis revealed statistically significant differences ( P< 0.05) between the delirium and non-delirium groups for several factors including age ≥ 65 years, blood transfusion, use of midazolam, use of adrenaline, APACHEⅡ score>15, SOFA score>4, metabolic acidosis, urea>7.1 mmol/L, coagulation disorders, lactate levels, and platelet count. Multivariate analysis identified age ≥ 65 years, use of midazolam, APACHEⅡ score>15, metabolic acidosis, urea>7.1 mmol/L, and coagulation disorders as independent risk factors for delirium in sepsis patients during ICU hospitalization.The predictive model was evaluated with an area under the ROC curve of 0.813, a non-significant Hosmer-Lemeshow goodness-of-fit test ( P=0.957>0.05), and a Brier score of 0.149 (<0.25), indicating good predictive performance and calibration. Clinical decision and impact curves demonstrated the model's favorable clinical applicability. Conclusions:The occurrence of delirium in ICU sepsis patients closely associate with six factors: age ≥ 65 years, use of midazolam, APACHEⅡ score>15, metabolic acidosis, urea>7.1 mmol/L, and coagulation disorders. This sepsis delirium prediction model has good clinical predictive ability and clinical applicability.

Objective:To summarize the clinical experience of using V-shaped incision to excise scalp subcutaneous tumors.Methods:A retrospective analysis of the clinical data of patients with subcutaneous benign tumors admitted to the Department of Burns and Plastic Surgery of the Northern Theater General Hospital from August 2020 to December 2021 was conducted. The tumors were all above 3 cm in diameter and closely adhered to surrounding tissues, and all were removed using a V-shaped incision. During the operation, the scalp was incised along the design line, the V-shaped skin flap was lifted to affiliate the tumor removed. The incision was closed directly from the tip of "V" until the moderate tension attained. The scalp flap was spread smoothly on the wound surface, and the excess scalp tissue was removed to form a Y-shaped suture. The flap survival, complications, incision scar, hair growth around the incision and tumor recurrence were observed and followed up after operation.Results:A total of 20 cases were included, including 12 males and 8 females, with an average medical history of (3.6±1.9) years and a tumor diameter of (4.1±1.1) cm. There were 8 sebaceous cysts, 5 lipomas, and 7 epidermoid cysts. After operation, 18 flaps survived well, and 2 cases had epidermal necrosis at the tip of the flap, which healed after dressing change. During the follow-up period of 6-12 months, 3 patients experienced local scalp numbness, which improved within 3-6 months. In 20 cases, the scalp was flat, the incision scar was not hyperplastic, the scar was short visually, the surrounding hair grew normally, and no tumor recurrence happened.Conclusion:V-shaped incision is relatively easy to expose the tumor and can accurately remove excess skin. After operation, the scalp has a good flat appearance, so it is an ideal choice for large scalp subcutaneous tumors with close adhesion to the surrounding tissue.

Objective:To summarize the clinical experience of using V-shaped incision to excise scalp subcutaneous tumors.Methods:A retrospective analysis of the clinical data of patients with subcutaneous benign tumors admitted to the Department of Burns and Plastic Surgery of the Northern Theater General Hospital from August 2020 to December 2021 was conducted. The tumors were all above 3 cm in diameter and closely adhered to surrounding tissues, and all were removed using a V-shaped incision. During the operation, the scalp was incised along the design line, the V-shaped skin flap was lifted to affiliate the tumor removed. The incision was closed directly from the tip of "V" until the moderate tension attained. The scalp flap was spread smoothly on the wound surface, and the excess scalp tissue was removed to form a Y-shaped suture. The flap survival, complications, incision scar, hair growth around the incision and tumor recurrence were observed and followed up after operation.Results:A total of 20 cases were included, including 12 males and 8 females, with an average medical history of (3.6±1.9) years and a tumor diameter of (4.1±1.1) cm. There were 8 sebaceous cysts, 5 lipomas, and 7 epidermoid cysts. After operation, 18 flaps survived well, and 2 cases had epidermal necrosis at the tip of the flap, which healed after dressing change. During the follow-up period of 6-12 months, 3 patients experienced local scalp numbness, which improved within 3-6 months. In 20 cases, the scalp was flat, the incision scar was not hyperplastic, the scar was short visually, the surrounding hair grew normally, and no tumor recurrence happened.Conclusion:V-shaped incision is relatively easy to expose the tumor and can accurately remove excess skin. After operation, the scalp has a good flat appearance, so it is an ideal choice for large scalp subcutaneous tumors with close adhesion to the surrounding tissue.

Objective:To investigate the effectiveness, safety, and advantages of modified radical neck dissection by gasless unilateral axillary approach (GUA-MRND) in the surgical management of selected patients with papillary thyroid cancer.Methods:We retrospectively analyzed patients with papillary thyroid cancer who underwent GUA-MRND (endoscopic group, n=16) versus unilateral open modified radical neck dissection (MRND) (open group, n=32) during the period from Jan. 2019 to Jun. 2021, including the differences in surgical efficiency, complication rate, and incisional satisfaction.Results:Compared MRND with GUA-MRND, the patients were younger ( P<0.05) , operative time and postoperative drainage anterior ( P<0.01) were slightly inferior in the latter, but it had obvious advantages in cervical swallowing discomfort and incision satisfaction evaluation ( P<0.05) . There was no significant difference in the incidence of temporary recurrent laryngeal nerve injury, intraoperative and postoperative bleeding, hematoma, infection, lymphatic or chylous leakage and supraclavicular numbness after surgery ( P>0.05) . The number of dissected lymph nodes in area II in the GUA-MRND was lower ( P<0.05) , but it was significantly higher ( P<0.01) in area III. And the average regional cleaning efficiency in the GUA-MRND was level Ⅲ (35.5%) , level Ⅵ (28.59%) , level Ⅳ (23.21%) , level Ⅱ (7.18%) and level Ⅴ (7.12%) , suggested that GUA-MRND had higher efficacy for level III, level Ⅵ and Level IV. Conclusion:GUA-MRND is safe, effective, and has high cosmetic satisfaction in the treatment of selected patients with lateral cervical lymph node metastases from papillary thyroid cancer.

Lung cancer tops the disease list in the world due to the high incidence and mortality， and about 85% of lung cancer cases is non-small cell lung cancer （NSCLC）. Most NSCLC patients are in the advanced stage at the time of diagnosis， with a low 5-year survival. Traditional Chinese medicine （TCM） plays a role in the comprehensive treatment of malignant tumors. Oral Chinese patent medicines， as an important part of TCM， have the advantages of stable preparations， mild taste， simple package， and accurate effective ingredients， which are different from decoctions. They have been widely used in the adjuvant treatment of NSCLC. In clinical practice， the combination of oral Chinese patent medicines with chemotherapy， targeted therapy， or radiotherapy， as well as the application of the oral Chinese patent medicines alone， can increase efficiency， reduce toxicity， prolong the survival time of patients， and improve the quality of life. The mechanisms of oral Chinese patent medicines in the treatment of NSCLC mainly include inhibiting the proliferation， invasion， and metastasis of lung cancer cells， promoting the apoptosis of lung cancer cells， inhibiting tumor neovascularization， reversing multidrug resistance， and regulating the immune functions， which reflects the multi-pathway and multi-target manner of TCM. The oral Chinese patent medicines commonly used in the clinical treatment of NSCLC include Jinfukang oral liquid， Shenyi capsules， Pingxiao capsules， Xiao'aiping tablets， Kanglaite capsules， compound Cantharis capsules， Huisheng oral liquid， Yangzheng Xiaoji capsules， Xihuang pills， Zilongjin tablets， and Cinobufagin capsules. There are many clinical and basic studies about the treatment of NSCLC with these medicines， while a systematic review remains to be carried out. Therefore， we systematically reviewed the mechanisms and clinical application of commonly used oral Chinese patent medicines in the adjuvant treatment of NSCLC， aiming to provide reference for follow-up research and clinical treatment.

Galactinol synthase (GolS) genes play important roles in plant response to abiotic stress. In this research, the plant expression vector of soybean GmGolS2-2 gene was constructed and transformed into tobacco to study the drought tolerance of transgenic tobacco. A GmGolS2-2 gene with 975 bp coding sequence was cloned from soybean leaves by reverse transcription-polymerase chain reaction (RT-PCR). GmGolS2-2 was linked to the plant expression vector pRI101 by restriction enzyme sites Nde Ⅰ and EcoR Ⅰ, and transformed into tobacco by leaf disc method. Genomic DNA PCR and real-time PCR showed that three GmGolS2-2 transgenic tobacco plants were obtained. The growth status of GmGolS2-2 transgenic tobacco under drought stress was better than that of wild-type tobacco. After drought stress treatment, the electrolyte leakage and malondialdehyde content of transgenic tobacco were lower than those of wild-type tobacco, but the proline content and soluble sugar content were higher than those of wild-type tobacco. The results of real-time PCR showed that the heterologous expression of GmGolS2-2 increased the expression of stress-related genes NtERD10C and NtAQP1 in transgenic tobacco. The above results indicated that GmGolS2-2 improved drought resistance of transgenic tobacco.
Drought Resistance ; Tobacco/genetics* ; Soybeans/genetics* ; Plant Proteins/metabolism* ; Plants, Genetically Modified/genetics* ; Stress, Physiological/genetics* ; Droughts ; Gene Expression Regulation, Plant