OBJECTIVE To observe the effect of the Chinese herbal compound Weidiao No.3 Formula(WD-3)combined with immunotherapy and chemotherapy on survival outcomes in patients with advanced non-small cell lung cancer(NSCLC)with lung-spleen qi dificiency type.METHODS A total of 216 patients with stage Ⅲb-Ⅳ NSCLC without driver gene mutations and with lung-spleen qi vacuity pattern and admitted to the oncology departments of Wuxi Hospital of Traditional Chinese Medicine and Jiangnan Uni-versity Affiliated Hospital between January 1,2020,and March 1,2025,were enrolled.Based on whether they received WD-3 oral treatment(≥3 months),they were divided into a Chinese medicine exposure group(n=98;WD-3+immunotherapy combined with chemo-therapy)and a non-exposure group(n=118;immunotherapy combined with chemotherapy alone).Propensity score matching(PSM)was used to balance baseline characteristics.Overall survival(OS),progression-free survival(PFS),and baseline characteristics were com-pared between the two groups.Cox proportional hazards regression model was used to analyze the association between exposure and outcome,and sensitivity analysis was performed.RESULTS After PSM,there were no statistically significant differences in baseline characteristics between the two groups(P>0.05).After matching,the median OS(32.92 months)and median PFS(9.07 months)in the Chinese medicine exposure group were longer than those in the non-exposure group(23.24 months and 7.89 months,respectively),with statistically significant differences(P<0.05).Multivariate analysis was conducted,incorporating age,PD-L1 expression,KPS score,pathological type,and other factors as covariates to assess the independent association between WD3 exposure and OS and PFS outcomes.The results indicated that WD3 exposure was statistically significant in reducing the risk of death(OS outcome)and disease progression(PFS outcome).Specifically,for the OS outcome,the HR was 0.626,with a 95%CI of 0.438 to 0.894,and P=0.01;for the PFS outcome,the HR was 0.721,with a 95%CI of 0.535 to 0.972,and P=0.032.Sensitivity analysis showed robust results(E-value>2.1).CONCLUSION WD-3 combined with immunotherapy and chemotherapy may prolong OS and PFS and reduce mortality risk in patients with advanced NSCLC without driver gene mutations and with lung-spleen qi dificiency type,achieves adequate therapeutic effects.

OBJECTIVE To observe the effect of the Chinese herbal compound Weidiao No.3 Formula(WD-3)combined with immunotherapy and chemotherapy on survival outcomes in patients with advanced non-small cell lung cancer(NSCLC)with lung-spleen qi dificiency type.METHODS A total of 216 patients with stage Ⅲb-Ⅳ NSCLC without driver gene mutations and with lung-spleen qi vacuity pattern and admitted to the oncology departments of Wuxi Hospital of Traditional Chinese Medicine and Jiangnan Uni-versity Affiliated Hospital between January 1,2020,and March 1,2025,were enrolled.Based on whether they received WD-3 oral treatment(≥3 months),they were divided into a Chinese medicine exposure group(n=98;WD-3+immunotherapy combined with chemo-therapy)and a non-exposure group(n=118;immunotherapy combined with chemotherapy alone).Propensity score matching(PSM)was used to balance baseline characteristics.Overall survival(OS),progression-free survival(PFS),and baseline characteristics were com-pared between the two groups.Cox proportional hazards regression model was used to analyze the association between exposure and outcome,and sensitivity analysis was performed.RESULTS After PSM,there were no statistically significant differences in baseline characteristics between the two groups(P>0.05).After matching,the median OS(32.92 months)and median PFS(9.07 months)in the Chinese medicine exposure group were longer than those in the non-exposure group(23.24 months and 7.89 months,respectively),with statistically significant differences(P<0.05).Multivariate analysis was conducted,incorporating age,PD-L1 expression,KPS score,pathological type,and other factors as covariates to assess the independent association between WD3 exposure and OS and PFS outcomes.The results indicated that WD3 exposure was statistically significant in reducing the risk of death(OS outcome)and disease progression(PFS outcome).Specifically,for the OS outcome,the HR was 0.626,with a 95%CI of 0.438 to 0.894,and P=0.01;for the PFS outcome,the HR was 0.721,with a 95%CI of 0.535 to 0.972,and P=0.032.Sensitivity analysis showed robust results(E-value>2.1).CONCLUSION WD-3 combined with immunotherapy and chemotherapy may prolong OS and PFS and reduce mortality risk in patients with advanced NSCLC without driver gene mutations and with lung-spleen qi dificiency type,achieves adequate therapeutic effects.

Objective:To explore the effect of exosomes released by Mycobacterium tuberculosis ( Mtb) Rv1983-stimulated macrophages on tuberculosis infection and its potential mechanism. Methods:Exosomes (Rv1983-M-Exo) released by macrophages following Mtb Rv1983 stimulation were extracted by hypervelocity centrifugation and then co-cultured with uninfected macrophages. Macrophage activity was detected by prodium iodide (PI) staining. The level of lipid reactive oxygen species (ROS) was detected by lipid peroxidation fluorescence probe. The expression of ferrous ions (Fe 2+ ) and malondialdehyde (MDA) were detected by colorimetry assay. The protein expression of acyl-CoA synthetase long chain family member 4 (ACSL4) in Rv1983-M-Exo was detected by Western blot. Exosomes (Rv1983-M+ siACSL4-Exo) were isolated from Rv1983-stimulated macrophages with interfered ACSL4 expression Rv1983 and co-cultured with uninfected macrophages. The effect of exosomes on the polarization of macrophages was detected by flow cytometry and Western blot. The effects of exosomes on phagocytosis and killing ability of macrophages were analyzed by plate colony assay and BCG-phagocytosis lysosome co-localization assay. Results:Compared with macrophage-derived exosomes (M-Exo), Rv1983-M-Exo promoted ferroptosis in uninfected macrophages, manifested by increased levels of intracellular lipid ROS, MDA and Fe 2+, which were significantly inhibited by ferroptosis inhibitor Fer-1. Rv1983 induced macrophages to release exosomes with high expression of ACSL4. Interfering the expression of ACSL4 in macrophages, the concentration of ACSL4 in the Rv1983-M+ siACSL4-Exo was significantly reduced. When the Rv1983-M+ siACSL4-Exo was co-cultured with uninfected macrophages, the ferroptosis of macrophages was significantly reduced. Rv1983-M-Exo promoted M2 macrophage polarization which showed up-regulation of CD206 and Arg1 expression, and decreased the phagocytosis and killing ability of macrophages, while Rv1983-M+ siACSL4-Exo or Fer-1 in combination with Rv1983-M-Exo reduced the expression of CD206 and Arg1 in macrophages, and promoted the phagocytosis and killing ability. Conclusions:Mtb Rv1983 protein up-regulates the level of ACSL4 in the exosomes secreted by macrophages, thereby inducing ferroptosis in uninfected macrophages, causing M2 polarization of macrophages, weakening phagocytosis and killing ability, and promoting Mtb infection.

Objective:To evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

ObjectiveTo investigate the effects of thyme herbal tea （BLX） on the proliferation of human coronavirus OC43 （HCoV-OC43） in vitro and in vivo. MethodThe chemical composition of BLX was analyzed by UPLC-MS. The cytotoxicity of BLX in HRT-18 cells and the effect of BLX treatment on the proliferation of HCoV-OC43 in cells were analyzed. Copies of viral gene were detected by real-time PCR. The effect of BLX treatment on the life cycle of HCoV-OC43 was detected by time-of-addition assay. The maximum tolerated dose of BLX and the influences of BLX on the body weight and survival time of suckling mice infected with HCoV-OC43 were determined. The expression of viral protein in the brain and lung tissue was analyzed by immunohistochemistry. ResultThere were 11 chemical components identified in BLX by UPLC-MS. BLX showed the 50% cytotoxic concentration （CC₅₀） of （13 859.56±319） mg·L^-1， the median inhibitory concentration （IC₅₀） of （1 439.09±200） mg·L^-1， and the selection index of 8.26-11.44 for HCoV-OC43 in HRT-18 cells. Compared with the cells infected with HCoV-OC43， BLX at the concentrations of 1 500， 1 000， 500 mg·L^-1 inhibited the proliferation of this virus （P<0.05， P<0.01）. BLX exhibited antiviral effect in the early stage of virus infection， and the inhibition role in the attachment stage was more significant than that in the entry stage （P<0.05）. In the suckling mice infected with HCoV-OC43， BLX at 1200 and 600 mg·kg^-1·d^-1 alleviated the symptoms， prolonged the survival period， reduced the death rate， and down-regulated the mRNA level of nucleocapsid protein in the mice. Moreover， BLX at 1 200 mg·kg^-1·d^-1 down-regulated the expression of nucleocapsid protein in the brain （P<0.01） and the lung （P<0.01）. ConclusionBLX contained multiple antiviral ingredients. It inhibited the proliferation of HCoV-OC43 both in vitro and in vivo by interference with viral attachment. This study provides theoretical reference for the treatment of acute respiratory tract infection with HCoV-OC43 and for further development and application of BLX.

Objective:To explore the correlation between functional constipation （FC）and its related factors with acute appendicitis（AA）in children，so as to provide a reference for the prevention and clinical diagnosis and treatment of children with AA. Methods:A case-control study was conducted on 170 children diagnosed with AA in the Department of Pediatrics，the Second Affiliated Hospital of Air Force Military Medical University，from August 2022 to March 2023，and 170 non-AA children during the same period were selected as control objects.The clinical data，incidence of FC，symptoms related to FC，Bristol stool classification，past constipation history and other information were compared between two groups.Results:The incidence of FC in 170 children with AA was 22.9%（39/170），which was significantly higher than 10.6%（18/170）in the non-AA group（ P<0.01）；For children under four years old，the proportion of faecal retention in AA group was higher than that in non-AA group（25.6% vs. 9.3%, P<0.05）；For children ≥ 4 years old，the proportion of faecal retention and dyschezia in AA group were higher than those in non-AA group（28.2% vs. 6.9%，29.0% vs. 16.4%，respectively,all P<0.05）.The proportion of past constipation history in AA group was higher than that in non-AA group（29.4% vs.14.1%）.The duration of constipation in AA group was longer than that in non-AA group [0.00（0.00，1.25）month vs. 0.00（0.00，0.00）month,all P<0.01].The proportion of children with low Bristol stool classification in AA group was higher than that in non-AA group（ P<0.01）.Multivariate Logistic regression analysis showed that faecal retention[ OR=6.186（95% CI 2.336~16.380）] and long constipation time [ OR=1.310（95% CI 1.095~1.567）]were independent risk factors for AA in children（all P<0.05）. Conclusion:The incidence of faecal retention in children with AA is higher than that in children without AA，and the median duration of constipation is longer than that in children without AA.Fecal retention and long-term constipation are independent risk factors for AA in children.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To investigate the efficacy and adverse reactions of whole-lung low-dose radiotherapy (LDRT) in patients with severe/critical coronavirus disease 2019 (COVID-19).Methods:Eight patients with severe/critical COVID-19 treated in the Jiangyin Hospital Affiliated to Nantong University from January to June 2023 who were treated with whole-lung LDRT after deteriorating or failing to improve post-medical treatment were enrolled in this single-arm phase I clinical trial. They received anterior-posterior penetrating radiation in a supine or prone position, with a total dose range from 0.5 to 1.5 Gy and a dose weight ratio of 1∶1. The oxygenation status, inflammatory markers, and imaging changes before and after radiotherapy were analyzed, and patients were followed up for acute radiation-induced adverse reactions.Results:One week after LDRT, the SaO 2/FiO 2 or PaO 2/FiO 2 indices increased in seven patients (87.5%), inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) decreased in seven patients (87.5%), and chest CT/chest radiographs revealed a significant reduction in the extent of pneumonia involvement in 5 patients (62.5%). No evident acute radiation-related adverse reactions were observed. Conclusions:Whole-lung LDRT with a dose range from 0.5 to 1.5 Gy can reduce inflammatory markers, improve clinical symptoms, and promote inflammatory absorption in patients with severe/critical COVID-19 who responded poorly to medical treatment while not inducing acute adverse reactions.

Objective:To explore the effect of exosomes released by Mycobacterium tuberculosis ( Mtb) Rv1983-stimulated macrophages on tuberculosis infection and its potential mechanism. Methods:Exosomes (Rv1983-M-Exo) released by macrophages following Mtb Rv1983 stimulation were extracted by hypervelocity centrifugation and then co-cultured with uninfected macrophages. Macrophage activity was detected by prodium iodide (PI) staining. The level of lipid reactive oxygen species (ROS) was detected by lipid peroxidation fluorescence probe. The expression of ferrous ions (Fe 2+ ) and malondialdehyde (MDA) were detected by colorimetry assay. The protein expression of acyl-CoA synthetase long chain family member 4 (ACSL4) in Rv1983-M-Exo was detected by Western blot. Exosomes (Rv1983-M+ siACSL4-Exo) were isolated from Rv1983-stimulated macrophages with interfered ACSL4 expression Rv1983 and co-cultured with uninfected macrophages. The effect of exosomes on the polarization of macrophages was detected by flow cytometry and Western blot. The effects of exosomes on phagocytosis and killing ability of macrophages were analyzed by plate colony assay and BCG-phagocytosis lysosome co-localization assay. Results:Compared with macrophage-derived exosomes (M-Exo), Rv1983-M-Exo promoted ferroptosis in uninfected macrophages, manifested by increased levels of intracellular lipid ROS, MDA and Fe 2+, which were significantly inhibited by ferroptosis inhibitor Fer-1. Rv1983 induced macrophages to release exosomes with high expression of ACSL4. Interfering the expression of ACSL4 in macrophages, the concentration of ACSL4 in the Rv1983-M+ siACSL4-Exo was significantly reduced. When the Rv1983-M+ siACSL4-Exo was co-cultured with uninfected macrophages, the ferroptosis of macrophages was significantly reduced. Rv1983-M-Exo promoted M2 macrophage polarization which showed up-regulation of CD206 and Arg1 expression, and decreased the phagocytosis and killing ability of macrophages, while Rv1983-M+ siACSL4-Exo or Fer-1 in combination with Rv1983-M-Exo reduced the expression of CD206 and Arg1 in macrophages, and promoted the phagocytosis and killing ability. Conclusions:Mtb Rv1983 protein up-regulates the level of ACSL4 in the exosomes secreted by macrophages, thereby inducing ferroptosis in uninfected macrophages, causing M2 polarization of macrophages, weakening phagocytosis and killing ability, and promoting Mtb infection.

Objective: To explore the direct⁃on⁃target micro⁃droplet growth assay (DOT⁃MGA) for rapid detection of the susceptibility of tigecycline and polymyxin. Methods: A total of 67 strains of Klebsiella pneumoniae were collected for DOT⁃MGA. 6 μl droplets with or without tigecycline or polymyxin (The final drug concentration is 2 μg/ml) were added in triplicate into the wells of the MALDI plate with four incubation time points (3 h ,4 h ,6 h , and 8 h) . The results were classified as susceptible (score < 1. 7) and non⁃susceptible (score≥1 . 7) according to the Bruker Biotype software Results: After incubation for 4 h , the growth efficiency, specificity and positive predictive value of tigecycline and polymyxin were both 100. 00% . The classification consistency rate was 98. 15% and 96. 15% , the sensitivity was 96. 30% and 92. 31% , and the negative predictive value was 96. 45% and 92. 86% , respectively. Conclusion DOT⁃MGA can provide rapid and reliable drug susceptibility diagnosis of tigecycline and polymyxin ,which is of great significance for the clinical anti⁃infective treatment.