ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer （NSCLC） based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/C/EBP homologous protein （CHOP） signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line （A549/cisplatin） were randomly divided into four groups： Blank control group （0.9% sodium chloride）， cisplatin group （5 µg·g^-1cisplatin）， Shenmai injection group （5.2 mg·g^-1 Shenmai injection）， and combination therapy group （5.2 mg·g^-1 Shenmai injection +5 µg·g^-1cisplatin）. The drug intervention lasted for 4 weeks， and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin （HE） staining was performed to observe tumor tissue pathology. Transmission electron microscopy （TEM） was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK， ATF4， and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein （BIP）， PERK， phosphorylated PERK （p-PERK）， eukaryotic translation initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， ATF4， CHOP， B-cell lymphoma -2 （Bcl-2）， and Bcl-2 Associated X protein （Bax）. A549/cis cells were divided into blank group： Blank control group （normal culture medium）， cisplatin group （23.3 µmol·L^-1 cisplatin）， Shenmai Injection group （20 g·L^-1 Shenmai injection）， and combination therapy group （20 g·L^-1 Shenmai injection+23.3 µmol·L^-1 cisplatin）. Cell counting kit-8 （CCK-8） method was used to detect cell viability， TEM was used to observe the morphology of endoplasmic reticulum， and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group， the combination therapy group showed increased body weight （P<0.05）， decreased tumor volume （P<0.05）， and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK， ATF4， and CHOP increased （P<0.05）. Western blot revealed elevated protein expression levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP， and Bax （P<0.05）， while Bcl-2 expression decreased （P<0.05）. As shown in the in vitro experiment， compared with the cisplatin group， the combination therapy group exhibited a reduced cell survival rate （P<0.05）. TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP and Bax （P<0.05）， with decreased Bcl-2 expression （P<0.05）. ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC， which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.

OBJECTIVE To compare the clinical efficacy and safety of remimazolam and propofol in general anesthesia induction and maintenance for elderly patients undergoing thoracoscopic lobectomy. METHODS A total of 86 elderly lung cancer patients who underwent thoracoscopic lobectomy at Chongqing University Three Gorges Hospital from February to July 2024 were selected and divided into the propofol group and the remimazolam group according to the randomized numerical table method， with 43 cases in each group. During anesthesia induction， patients in the propofol group and the remimazolam group were intravenously administered 2 mg/kg of Propofol medium- and long-chain fat emulsion injection or 0.25 mg/kg of Remimazolam tosilate for injection， respectively； during anesthesia maintenance， the two groups received intravenous infusion of 6-10 mg/（kg·h） of Propofol medium- and long- chain fat emulsion injection or 1-3 mg/（kg·h） of Remimazolam tosilate for injection， respectively. The anesthesia effects， anesthesia-related indicators， intraoperative opioid and muscle relaxant dosages， Ramsay sedation score， numerical rating scale （NRS） score， and hemodynamic parameters were compared between the two groups， and the occurrence of adverse drug reactions was recorded. RESULTS A total of 41 patients in the propofol group and 43 patients in the remimazolam group completed the trial. The proportion of patients with grade Ⅰ anesthesia effect in the remimazolam group was significantly higher than that in the propofol group， while the proportion of patients with grade Ⅱ anesthesia effect was significantly lower than that in the propofol group （P＜0.05）. In this group， the disappearance time of eyelash reflex， the time taken for the bispectral index to drop to 60， and the Ramsay sedation scores （2 and 6 hours after operation） were all significantly prolonged or increased， while the recovery time， NRS scores （2 and 6 hours after operation）， and the incidence of intraoperative hypotension were all significantly shortened or reduced； moreover， the improvements of the above sedation/NRS scores exhibited a time-dependent pattern within 2 to 24 hours after operation （P＜0.05）. Compared with before anesthesia induction （T0）， the heart rate [except at 2 min after medication （T1）， 60 min after anesthesia （T4）， and at the end of surgery （T5） in the remimazolam group] and mean arterial pressure [except at T1 in the remimazolam group] of patients in both groups significantly decreased at T1， 5 min after medication （T2）， at the start of surgery （T3）， T4， and T5 （P＜0.05）. Meanwhile， regional cerebral oxygen saturation significantly increased in both groups. Furthermore， the heart rate and mean arterial pressure of patients in the remimazolam group were significantly higher than those in the propofol group at T1， T2 and T4 （P＜0.05）. No statistically significant differences were observed between the two groups in terms of postanesthesia care unit stay time， dosage of opioids and muscle relaxants， regional cerebral oxygen saturation， or peripheral oxygen saturation at various time points （P＞0.05）. CONCLUSIONS Compared to propofol， remimazolam demonstrates superior anesthesia effects when used for the induction and maintenance of general anesthesia in elderly patients undergoing thoracoscopic lobectomy. It not only provides more stable intraoperative hemodynamics and shortens the postoperative recovery time but also effectively reduces the incidence of intraoperative hypotension.

[Purpose]To analyze the disease burden of malignant tumors and its changing trends in Chinese and global non-smoking female population from 1990 to 2021.[Methods]Data of mortality and disability-adjusted life year(DALY)due to malignant tumors for Chinese and global non-smoking female malignant tumors from 1990 to 2021 were extracted from the Global Burden of Disease Study 2021(GBD 2021),and the average annual percentage change(AAPC)were calculated using Joinpoint regression model.[Results]From 1990 to 2021,the number of deaths for malignant tu-mors in Chinese non-smoking female population increased from 13.7 1×104 to 26.8 1×104,with a higher increased trend compared with the global(China:AAPC=2.19％,95％CI:2.06％～2.33％;Global:AAPC=1.92％,95％CI:1.80％～2.04％,P=0.003);the age-standardized mortality rate decreased from 32.42/105 to 24.58/105,with a higher decreased trend compared with the global(China:AAPC=-0.88％,95％CI:-1.00％～-0.76％;Global:AAPC=-0.59％,95％CI:-0.68％～-0.51％,P＜0.001).From 1990 to 2021,the DALY for malignant tumors in Chinese non-smoking female population increased from 412.96×104 to 691.20×104 person-years,with a similar changing trend compared with the global(China:AAPC=1.68％,95％CI:1.56％～1.81％,Global:AAPC=1.63％,95％CI:1.52％～1.75％,P=0.536);the age-standardized DALY rate in Chinese non-smoking female population decreased from 889.58/105 to 642.65/105,with a higher decreased trend compared with the global(China:AAPC=-1.04％,95％CI:-1.15％～-0.92％;Global:AAPC=-0.69％,95％CI:-0.78％～-0.61％,P＜0.001).The top five malignant tumors of high age-standardized mor-tality rate in Chinese non-smoking female population in 2021 were tracheal,bronchus and lung cancer,colon and rectum cancer,cervical cancer,breast cancer,and liver cancer.The top five malignant tumors of high age-standardized mortality rate globally in 2021 were cervical cancer,colon and rectum cancer,breast cancer,tracheal,bronchus and lung cancer,and pancreatic cancer.The age-standardized mortality rate and DALY rate of breast cancer,liver cancer,pan-creatic cancer and corpus cancer showed overall upward trends(all P＜0.05).[Conclusion]From 1990 to 2021,the number of deaths and DALY of malignant tumors in Chinese and global non-smoking female population showed overall increased trends,and age-standardized mortality rate and DALY rate showed overall decreased trends.In future,more targeted cancer prevention measures are needed to reduce the disease burden of malignant tumors in non-smoking female population.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

ObjectiveTo develop a scale for evaluating the syndrome of internal retention of dampness and turbidity in nonalcoholic fatty liver disease （NAFLD） that combines disease and syndrome and has the characteristics of traditional Chinese medicine （TCM）. MethodsAn item pool was established for evaluating the syndrome of internal retention of dampness and turbidity in nonalcoholic fatty liver disease （NAFLD） with reference to the guideline for developing international scales. A clinical survey was conducted among the outpatients and inpatients who were diagnosed with NAFLD and had the syndrome of internal retention of dampness and turbidity in Department of Hepatology and Spleen-Stomach， The First Affiliated Hospital of Henan University of Chinese Medicine， from June to August， 2023， and the items were screened based on the classical test theory and the item response theory. An expert questionnaire was developed， and expert discussions were conducted using the Delphi method to identify the items for evaluating the syndrome of internal retention of dampness and turbidity in NAFLD. Finally， the scale was given scientific scores. ResultsA preliminary item pool was established， with 16 primary items and 22 secondary items， and it was divided into the two dimensions of disease and syndrome type. Clinical pre-survey suggested to retain 9 primary items and 14 secondary items， while the Delphi expert questionnaire recommended to retain 11 primary items and 15 secondary items， and tongue manifestation and pulse manifestation were no longer used for assessing the severity of syndrome. After hierarchical analysis and scientific assignment of scores， the scale for evaluating the syndrome of internal retention of dampness and turbidity in NAFLD had a total score of 123 points and 9 important items， i.e.， discomfort in the hypochondrium， abdominal fullness and distension， obesity， heaviness of the head and body， loose stool， anorexia， coughing up phlegm， nausea with a tendency to vomit， and lethargy. ConclusionA preliminary scale is established for evaluating the syndrome of internal retention of dampness and turbidity in NAFLD， which fills the gap in this research field and provides a basis for further clinical application.

[Purpose]To analyze the disease burden of malignant tumors and its changing trends in Chinese and global non-smoking female population from 1990 to 2021.[Methods]Data of mortality and disability-adjusted life year(DALY)due to malignant tumors for Chinese and global non-smoking female malignant tumors from 1990 to 2021 were extracted from the Global Burden of Disease Study 2021(GBD 2021),and the average annual percentage change(AAPC)were calculated using Joinpoint regression model.[Results]From 1990 to 2021,the number of deaths for malignant tu-mors in Chinese non-smoking female population increased from 13.7 1×104 to 26.8 1×104,with a higher increased trend compared with the global(China:AAPC=2.19％,95％CI:2.06％～2.33％;Global:AAPC=1.92％,95％CI:1.80％～2.04％,P=0.003);the age-standardized mortality rate decreased from 32.42/105 to 24.58/105,with a higher decreased trend compared with the global(China:AAPC=-0.88％,95％CI:-1.00％～-0.76％;Global:AAPC=-0.59％,95％CI:-0.68％～-0.51％,P＜0.001).From 1990 to 2021,the DALY for malignant tumors in Chinese non-smoking female population increased from 412.96×104 to 691.20×104 person-years,with a similar changing trend compared with the global(China:AAPC=1.68％,95％CI:1.56％～1.81％,Global:AAPC=1.63％,95％CI:1.52％～1.75％,P=0.536);the age-standardized DALY rate in Chinese non-smoking female population decreased from 889.58/105 to 642.65/105,with a higher decreased trend compared with the global(China:AAPC=-1.04％,95％CI:-1.15％～-0.92％;Global:AAPC=-0.69％,95％CI:-0.78％～-0.61％,P＜0.001).The top five malignant tumors of high age-standardized mor-tality rate in Chinese non-smoking female population in 2021 were tracheal,bronchus and lung cancer,colon and rectum cancer,cervical cancer,breast cancer,and liver cancer.The top five malignant tumors of high age-standardized mortality rate globally in 2021 were cervical cancer,colon and rectum cancer,breast cancer,tracheal,bronchus and lung cancer,and pancreatic cancer.The age-standardized mortality rate and DALY rate of breast cancer,liver cancer,pan-creatic cancer and corpus cancer showed overall upward trends(all P＜0.05).[Conclusion]From 1990 to 2021,the number of deaths and DALY of malignant tumors in Chinese and global non-smoking female population showed overall increased trends,and age-standardized mortality rate and DALY rate showed overall decreased trends.In future,more targeted cancer prevention measures are needed to reduce the disease burden of malignant tumors in non-smoking female population.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective Investigate the expression level and clinical significance of microRNA-223-3p(miR-223-3p)in the serum of pregnant women with preterm premature rupture of membranes(PPROM).Methods A total of 91 pregnant women who underwent cesarean delivery at the Xuzhou Maternal and Child Health Hospital affiliated with Xuzhou Medical University between April and September 2023 were selected for the study.This included 60 cases of PPROM and 31 cases of term normal pregnant women as the research subjects.The study group was divided based on the pathological results of the membranes into:PPROM group without histological chorioamnionitis(HCA)(PPROM group,n = 37),and PPROM group with HCA(PPROM+HCA group,n = 23).Serum samples from pregnant women were collected before hospital treatment,and the expression level of miR-223-3p in the serum was detected by quantitative real-time PCR(qRT-PCR).The levels of inflammatory factors such as IL-1β,IL-6,IL-8,and TNF-α in the serum were measured by enzyme-linked immunosorbent assay(ELISA).Results The expression level of miR-223-3p in the serum of the PPROM+HCA group was significantly higher than that of the PPROM group and the normal group(P＜0.05).The expression levels of IL-1β,IL-6,IL-8,and TNF-α in the serum of the PPROM+HCA group were also significantly higher than those of the PPROM group and the normal group(P＜0.05).There was a positive correlation between the expression level of miR-223-3p in the serum of the PPROM+HCA group and the expression levels of IL-1β,IL-6,IL-8,and TNF-α(r = 0.553,0.505,0438,0.656,P＜0.05).Conclusion The upregulation of miR-223-3p in the serum of pregnant women with PPROM+HCA is associated with the severity of inflammation in PPROM.

AIM:To investigate the effects of the γ-aminobutyric acid(GABAergic)neural pathway from the anterior cingulate cortex(ACC)to the nucleus accumbens(NAc)on the regulation of irritable bowel syndrome(IBS)and its underlying mechanisms in mice.METHODS:(1)A C57BL/6J mice model of IBS was established by using chronic acute combing stress(CACS).The mice were divided into a normal group and an IBS group(n=8).The presence of IBS-like symptoms was determined through behavioural tests,an intestinal motility test and abdominal withdrawal reflex scores.(2)Fluorescence gold(FG)retrograde tracing and immunohistochemistry were used to investigate the ACC-NAc GABAergic neural pathway and to examine the activation of GABA in the ACC in IBS mice(n=8).(3)A total of 1.5 μL of normal saline(NS),GABAA receptor antagonist bicuculline(BIC)or agonist isoguvacine hydrochloride(Isog)was ad-ministered via a preburied catheter into the NAc of mice in IBS and normal groups.The mice were randomly divided into three groups(n=8):NS group,BIC group and Isog group.IBS-like symptoms were assessed.(4)The mice were prein-jected with AAV2/9-mDlx-iCre-WPRE-pA in the ACC and AAV2/2Retro Plus-hSyn-DIO-hM3D(Gq)-eGFP-WPRE-pA in the NAc and subsequently divided into four groups(n=8):NS(intraperitoneal injection)+NS(NAc microinjection)group,NS+BIC group,clozapine N-oxide(CNO)+NS group and CNO+BIC group.The mice who received AAV2/2Retro-hSyn-DIO-hM4D(Gi)-EGFP-WPRE-pA in the NAc were randomly divided into three groups(n=8):NS+NS group,NS+BIC group and CNO+NS group.Enzyme-linked immunosorbent assay(ELISA)was employed to estimate the expression levels of histamine and 5-hydroxytryptamine(5-HT)in colon tissue,and the effects of GABAergic neural pathways from ACC to NAc on IBS were studied.RESULTS:CACS induced IBS-like symptoms in mice.The results of FG retrograde tracing combined with fluorescence immunohistochemistry showed that GABA neurons of ACC could project to NAc.The injection of BIC in the NAc was found to significantly reduce anxiety-like behaviours,diarrheal symptoms and visceral hy-persensitivity in the IBS mice(P<0.05).Chemogenetic inhibition of the ACC-NAc GABAergic neurons ameliorated IBS-like symptoms in mice(P<0.05).CONCLUSION:The GABAergic pathway of ACC-NAc might be involved in the regu-lation of IBS in mice,which may be related to the release of histamine and 5-HT in colon tissue.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.