Objectives:To investigate the incidence of tyrosine kinase inhibitor (TKI) withdrawal syndrome and psychological issues, and their associated factors, in patients with chronic-phase chronic myeloid leukemia (CML-CP) after TKI discontinuation.Methods:We retrospectively analyzed the clinical data of CML-CP patients who discontinued TKI therapy at Peking University People's Hospital after September 2012. Logistic regression models were used to identify independent factors associated with the occurrence of TKI withdrawal syndrome and psychological issues.Results:A total of 158 patients were included, of whom 92 (58%) were female. The median age at discontinuation was 50 ( IQR, 35-60) years. With a median follow-up of 25 ( IQR, 11-49) months, the 4-year rate of sustained major molecular response (MMR) was 60% (95% CI: 51%-70%) . Fifty-one (32%) patients experienced TKI withdrawal syndrome at a median of 1.3 ( IQR, 0.5-2.0) months after TKI discontinuation. Fifty-one (32%) patients reported psychological issues such as anxiety. These concerns stemmed from fears of fluctuating BCR::ABL1 levels or disease relapse, and, for those who discontinued TKI for pregnancy, worries about adverse fetal effects and/or the fetus inheriting CML. Multivariable analyses revealed that older age at discontinuation [ P=0.003 when adjusting for TKI therapy duration; P=0.002 when adjusting for deep molecular response (DMR) duration], longer TKI therapy duration ( P=0.010) , and longer DMR duration before discontinuation ( P=0.005) were significantly associated with a higher risk of TKI withdrawal syndrome; a university degree or higher ( P=0.010) and TKI discontinuation due to pregnancy or adverse events ( P=0.001) were significantly associated with psychological issues after discontinuation. The occurrence of TKI withdrawal syndrome or psychological issues had no impact on the probability of major molecular response loss after discontinuation. Conclusion:TKI withdrawal syndrome and psychological issues are common in CML patients who discontinue TKI therapy. Older age at discontinuation and longer TKI therapy duration or DMR duration are significantly associated with TKI withdrawal syndrome. Higher education level and TKI discontinuation due to pregnancy or adverse events are significantly associated with psychological issues.

Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.

Objective:To explore the genetic etiology of a child with Renpenning syndrome (RS), and review the literature on the clinical characteristics and gene mutations of RS.Methods:A child with RS (patient 1) who was diagnosed and treated in the Pediatric Intensive Care Unit of the Third Affiliated Hospital of Zhengzhou University in November 2023 was selected as the research object. The medical history, family history, physical examination, cerebrospinal fluid examination, echocardiography, brain magnetic resonance imaging (MRI), brain magnetic resonance angiography, cardiac coronary CT angiography and intelligence quotient (IQ) score of child 1 were retrospectively collected. Peripheral venous blood samples were collected from patient 1, his parents, sister and brother, respectively. Genomic DNA was extracted from the child and his family members, and three-whole exome sequencing (Trios-WES) was performed. Sanger sequencing was used to verify the pedigree. Bioinformatics softwares (Mutation Taster, REVEL, SIFT, PolyPhen-2, GERP+ +, SWISS-MODEL) were applied. The pathogenicity of the detected variants was rated according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Classification of Genetic Variants (hereinafter referred to as the ACMG Guidelines). " PQBP1 gene" " Renpenning syndrome" " PQBP1 gene" " Renpenning syndrome" were used as keywords in Chinese and English, respectively. Case reports of patients with RS caused by PQBP1 gene variants were retrieved from Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed database. The clinical features and gene variants of RS caused by PQBP1 gene variants were summarized and analyzed. This study was reviewed by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Approval No. 2024-334-01). Results:The patient 1, a 12-year-old boy, was admitted to the hospital due to fever and disturbance of consciousness. Cerebrospinal fluid test showed viral encephalitis caused by human herpesvirus 7 infection. The main clinical manifestations were unusual facies (microcephaly, long narrow face, microphthalmos, superior oblique palpebral fissure, hypertelorism of inner canthus, bulbous nasal columella) and mental retardation. Auxiliary examination showed than patient 1 had atrial septal defect, nodular heterotopia in the posterior horn of the left ventricle, angiodysplasia, and low IQ. The disease began in infancy, and there was no family history of related diseases. A hemizygous deletion, c. 459_462del (p.Arg153SerfsTer41), was identified in exon 5 of the PQBP1 gene in patient 1, which was inherited from his mother by Sanger sequencing. The results of bioinformatics analysis showed that the mutation was harmful. This variant was rated as pathogenic (PVS1+ PS4+ PM2_Supporting+ PP3) according to ACMG Guidelines. According to the literature search strategy set in this study, a total of 13 cases of RS were retrieved, involving 16 cases of RS patient caused by PQBP1 gene mutation (patients 2-17), including patient 1, a total of 17 cases of RS. Among the 17 patients, 16 male patients had hemizygous mutations in the X chromosome PQBP1 gene, and 1 female patient had heterozygous mutations, including 12 deletion frameshift nonsense mutations, 3 point missense mutations, and 2 duplication mutations. Except for two fetuses, all patients had special facial features and low IQ to varying degrees. Ten patients had abnormal development of one or more organs such as eyes, heart, brain, etc. Conclusion:The main clinical manifestations of RS are developmental delay, long narrow face, bulbous nose, microcephaly, and may be accompanied by heterotopia of gray matter of ventricle and congenital heart disease. The c. 459_462del (p.Arg153SerfsTer41) variant of the PQBP1 gene is the genetic basis of patient 1 in this study.

OBJECTIVE: To explore the genetic etiology of a child with Renpenning syndrome (RS), and review the literature on the clinical characteristics and gene mutations of RS. METHODS: A child with RS (patient 1) who was diagnosed and treated in the Pediatric Intensive Care Unit of the Third Affiliated Hospital of Zhengzhou University in November 2023 was selected as the research object. The medical history, family history, physical examination, cerebrospinal fluid examination, echocardiography, brain magnetic resonance imaging (MRI), brain magnetic resonance angiography, cardiac coronary CT angiography and intelligence quotient (IQ) score of child 1 were retrospectively collected. Peripheral venous blood samples were collected from patient 1, his parents, sister and brother, respectively. Genomic DNA was extracted from the child and his family members, and Trios-whole exome sequencing (Trios-WES) was performed. Sanger sequencing was used to verify the pedigree. Bioinformatics softwares (Mutation Taster, REVEL, SIFT, PolyPhen-2, GERP++, SWISS-MODEL) were applied. The pathogenicity of the detected variants was rated according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Classification of Genetic Variants (hereinafter referred to as the ACMG Guidelines). "PQBP1 gene" "Renpenning syndrome" "PQBP1 gene" "Renpenning syndrome" were used as keywords in Chinese and English, respectively. Case reports of patients with RS caused by PQBP1 gene variants were retrieved from Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed database. The clinical features and gene variants of RS caused by PQBP1 gene variants were summarized and analyzed. This study was reviewed by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Approval No. 2024-334-01). RESULTS The patient 1, a 12-year-old boy, was admitted to the hospital due to fever and disturbance of consciousness. Cerebrospinal fluid test showed viral encephalitis caused by human herpesvirus 7 infection. The main clinical manifestations were unusual facies (microcephaly, long narrow face, microphthalmos, superior oblique palpebral fissure, hypertelorism of inner canthus, bulbous nasal columella) and mental retardation. Auxiliary examination showed than patient 1 had atrial septal defect, nodular heterotopia in the posterior horn of the left ventricle, angiodysplasia, and low IQ. The disease began in infancy, and there was no family history of related diseases. A hemizygous deletion, c.459_462del (p.Arg153SerfsTer41), was identified in exon 5 of the PQBP1 gene in patient 1, which was inherited from his mother by Sanger sequencing. The results of bioinformatics analysis showed that the mutation was harmful. This variant was rated as pathogenic (PVS1+PS4+PM2_Supporting+PP3) according to ACMG Guidelines. According to the literature search strategy set in this study, a total of 13 cases of RS were retrieved, involving 16 cases of RS patient caused by PQBP1 gene mutation (patients 2-17), including patient 1, a total of 17 cases of RS. Among the 17 patients, 16 male patients had hemizygous mutations in the X chromosome PQBP1 gene, and 1 female patient had heterozygous mutations, including 12 deletion frameshift nonsense mutations, 3 point missense mutations, and 2 duplication mutations. Except for two fetuses, all patients had special facial features and low IQ to varying degrees. Ten patients had abnormal development of one or more organs such as eyes, heart, brain, etc. CONCLUSION: The main clinical manifestations of RS are developmental delay, long narrow face, bulbous nose, microcephaly, and may be accompanied by heterotopia of gray matter of ventricle and congenital heart disease. The c.459_462del (p.Arg153SerfsTer41) variant of the PQBP1 gene is the genetic basis of patient 1 in this study.
Humans ; Male ; Mutation ; Pedigree ; Child ; DNA-Binding Proteins/genetics* ; Nuclear Proteins/genetics* ; Female ; Exome Sequencing

Objective To investigae microbial community structure of lower respiratory tract in severe hospital-acquired pneumonia(SHAP)patients in intensive care unit(ICU)using metagenomic next-generation sequencing(mNGS).Methods mNGS was performed on bronchoalveolar lavage fluid(BALF)of 84 patients with SHAP.Patients were grouped based on age,smoking status,underlying diseases and duration of artificial airway.The differences in α diversity,β diversity,microbial composition and community structure of airway microbiota were compared between different groups.The differential airway microbiota associated with artificial airway were screened,and microbial co-occurrence networks was constructed to observe the interaction in microorganisms.Results Results of α diversity analysis revealed that diversity and evenness of the microbial community were higher in young adults compared to those of middle-aged patients,while microbial diversity and evenness were significantly reduced in patients with comorbid stroke.In the group of artificial airway treatment,the diversity and uniformity of microorganisms decreased as the duration of artificial airway treatment increased.The diversity was the lowest when the artificial airway treatment lasted for more than 3 days.β diversity analysis confirmed that there were significant differences in the distinct microbial community structures between the>3 days support group and the non-intubated and≤3 days support cohorts.Acinetobacter baumannii was dominant in all groups.The bacterial diversity was significantly higher in the middle-aged group,the non-smoking group,the group without artificial airway therapy,the group without diabetes mellitus,the group with artificial airway therapy≥3 days and the group with chronic lung disease than those of other groups.In particular,pseudomonas aeruginosa,corynebacterium striatum and veillonella parvula were enriched in these groups.Difference analysis showed that there were significant differences in pseudomonas aeruginosa and corynebacterium striatum between the group with artificial airway treatment>3 days,the group without artificial airway therapy and the group with artificial airway treatment≤3 days.Network co-occurrence showed that there may be synergistic or antagonistic relationships between some microorganisms.Conclusion The microbial diversity of the lower respiratory tract in patients with SHAP significantly decreases in the elderly,those with concurrent stroke and those receiving artificial airway treatment.For these groups,rational use of antibiotics should be adopted to guide precise anti-infection treatment.

Objective To investigae microbial community structure of lower respiratory tract in severe hospital-acquired pneumonia(SHAP)patients in intensive care unit(ICU)using metagenomic next-generation sequencing(mNGS).Methods mNGS was performed on bronchoalveolar lavage fluid(BALF)of 84 patients with SHAP.Patients were grouped based on age,smoking status,underlying diseases and duration of artificial airway.The differences in α diversity,β diversity,microbial composition and community structure of airway microbiota were compared between different groups.The differential airway microbiota associated with artificial airway were screened,and microbial co-occurrence networks was constructed to observe the interaction in microorganisms.Results Results of α diversity analysis revealed that diversity and evenness of the microbial community were higher in young adults compared to those of middle-aged patients,while microbial diversity and evenness were significantly reduced in patients with comorbid stroke.In the group of artificial airway treatment,the diversity and uniformity of microorganisms decreased as the duration of artificial airway treatment increased.The diversity was the lowest when the artificial airway treatment lasted for more than 3 days.β diversity analysis confirmed that there were significant differences in the distinct microbial community structures between the>3 days support group and the non-intubated and≤3 days support cohorts.Acinetobacter baumannii was dominant in all groups.The bacterial diversity was significantly higher in the middle-aged group,the non-smoking group,the group without artificial airway therapy,the group without diabetes mellitus,the group with artificial airway therapy≥3 days and the group with chronic lung disease than those of other groups.In particular,pseudomonas aeruginosa,corynebacterium striatum and veillonella parvula were enriched in these groups.Difference analysis showed that there were significant differences in pseudomonas aeruginosa and corynebacterium striatum between the group with artificial airway treatment>3 days,the group without artificial airway therapy and the group with artificial airway treatment≤3 days.Network co-occurrence showed that there may be synergistic or antagonistic relationships between some microorganisms.Conclusion The microbial diversity of the lower respiratory tract in patients with SHAP significantly decreases in the elderly,those with concurrent stroke and those receiving artificial airway treatment.For these groups,rational use of antibiotics should be adopted to guide precise anti-infection treatment.

Objective:To explore the genetic etiology of a child with Renpenning syndrome (RS), and review the literature on the clinical characteristics and gene mutations of RS.Methods:A child with RS (patient 1) who was diagnosed and treated in the Pediatric Intensive Care Unit of the Third Affiliated Hospital of Zhengzhou University in November 2023 was selected as the research object. The medical history, family history, physical examination, cerebrospinal fluid examination, echocardiography, brain magnetic resonance imaging (MRI), brain magnetic resonance angiography, cardiac coronary CT angiography and intelligence quotient (IQ) score of child 1 were retrospectively collected. Peripheral venous blood samples were collected from patient 1, his parents, sister and brother, respectively. Genomic DNA was extracted from the child and his family members, and three-whole exome sequencing (Trios-WES) was performed. Sanger sequencing was used to verify the pedigree. Bioinformatics softwares (Mutation Taster, REVEL, SIFT, PolyPhen-2, GERP+ +, SWISS-MODEL) were applied. The pathogenicity of the detected variants was rated according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Classification of Genetic Variants (hereinafter referred to as the ACMG Guidelines). " PQBP1 gene" " Renpenning syndrome" " PQBP1 gene" " Renpenning syndrome" were used as keywords in Chinese and English, respectively. Case reports of patients with RS caused by PQBP1 gene variants were retrieved from Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed database. The clinical features and gene variants of RS caused by PQBP1 gene variants were summarized and analyzed. This study was reviewed by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Approval No. 2024-334-01). Results:The patient 1, a 12-year-old boy, was admitted to the hospital due to fever and disturbance of consciousness. Cerebrospinal fluid test showed viral encephalitis caused by human herpesvirus 7 infection. The main clinical manifestations were unusual facies (microcephaly, long narrow face, microphthalmos, superior oblique palpebral fissure, hypertelorism of inner canthus, bulbous nasal columella) and mental retardation. Auxiliary examination showed than patient 1 had atrial septal defect, nodular heterotopia in the posterior horn of the left ventricle, angiodysplasia, and low IQ. The disease began in infancy, and there was no family history of related diseases. A hemizygous deletion, c. 459_462del (p.Arg153SerfsTer41), was identified in exon 5 of the PQBP1 gene in patient 1, which was inherited from his mother by Sanger sequencing. The results of bioinformatics analysis showed that the mutation was harmful. This variant was rated as pathogenic (PVS1+ PS4+ PM2_Supporting+ PP3) according to ACMG Guidelines. According to the literature search strategy set in this study, a total of 13 cases of RS were retrieved, involving 16 cases of RS patient caused by PQBP1 gene mutation (patients 2-17), including patient 1, a total of 17 cases of RS. Among the 17 patients, 16 male patients had hemizygous mutations in the X chromosome PQBP1 gene, and 1 female patient had heterozygous mutations, including 12 deletion frameshift nonsense mutations, 3 point missense mutations, and 2 duplication mutations. Except for two fetuses, all patients had special facial features and low IQ to varying degrees. Ten patients had abnormal development of one or more organs such as eyes, heart, brain, etc. Conclusion:The main clinical manifestations of RS are developmental delay, long narrow face, bulbous nose, microcephaly, and may be accompanied by heterotopia of gray matter of ventricle and congenital heart disease. The c. 459_462del (p.Arg153SerfsTer41) variant of the PQBP1 gene is the genetic basis of patient 1 in this study.

Objectives:To investigate the incidence of tyrosine kinase inhibitor (TKI) withdrawal syndrome and psychological issues, and their associated factors, in patients with chronic-phase chronic myeloid leukemia (CML-CP) after TKI discontinuation.Methods:We retrospectively analyzed the clinical data of CML-CP patients who discontinued TKI therapy at Peking University People's Hospital after September 2012. Logistic regression models were used to identify independent factors associated with the occurrence of TKI withdrawal syndrome and psychological issues.Results:A total of 158 patients were included, of whom 92 (58%) were female. The median age at discontinuation was 50 ( IQR, 35-60) years. With a median follow-up of 25 ( IQR, 11-49) months, the 4-year rate of sustained major molecular response (MMR) was 60% (95% CI: 51%-70%) . Fifty-one (32%) patients experienced TKI withdrawal syndrome at a median of 1.3 ( IQR, 0.5-2.0) months after TKI discontinuation. Fifty-one (32%) patients reported psychological issues such as anxiety. These concerns stemmed from fears of fluctuating BCR::ABL1 levels or disease relapse, and, for those who discontinued TKI for pregnancy, worries about adverse fetal effects and/or the fetus inheriting CML. Multivariable analyses revealed that older age at discontinuation [ P=0.003 when adjusting for TKI therapy duration; P=0.002 when adjusting for deep molecular response (DMR) duration], longer TKI therapy duration ( P=0.010) , and longer DMR duration before discontinuation ( P=0.005) were significantly associated with a higher risk of TKI withdrawal syndrome; a university degree or higher ( P=0.010) and TKI discontinuation due to pregnancy or adverse events ( P=0.001) were significantly associated with psychological issues after discontinuation. The occurrence of TKI withdrawal syndrome or psychological issues had no impact on the probability of major molecular response loss after discontinuation. Conclusion:TKI withdrawal syndrome and psychological issues are common in CML patients who discontinue TKI therapy. Older age at discontinuation and longer TKI therapy duration or DMR duration are significantly associated with TKI withdrawal syndrome. Higher education level and TKI discontinuation due to pregnancy or adverse events are significantly associated with psychological issues.

Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.

AIM:To investigate the effects of saponin from Panax japonicus IVa(SPJ IVa)on acute lung inju-ry in rats and to explore its possible protective mechanism.METHODS:Sixty SD rats were randomly divided into four groups,15 rats in each group:the control group,model group,low-dose SPJ IVa group,and high-dose SPJ IVa group.A rat model of ALI was established via intratracheal instillation of lipopolysaccharide(LPS,2 mg/kg).Rats in the low-and high-dose SPJ IVa groups were intraperitoneally injected with 15 and 45 mg/kg SPJ IVa,respectively,30 min after model-ing.Serum,bronchoalveolar lavage fluid(BALF),and lungs were collected 24 h after modeling.Pathomorphological changes in lung tissues were assessed using HE staining.The wet weight/dry weight ratio of lung tissues was measured us-ing the weighing method,whereas ELISA was used to measure the levels of interleukin-1β(IL-1β),IL-6,and tumor ne-crosis factor-α(TNF-α)in the serum and BALF.The levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione(GSH)were assessed using the kit method.Cell apoptosis in lung tissues was evaluated by immunohisto-chemical staining of cleaved caspase-3 and TUNEL.Western blot was used to measure the expression of nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),nuclear factor-κB(NF-κB)p65,and Toll-like receptor 4(TLR4)in lung tissues.RESULTS:Compared with control group,the lung tissues of the model group were significantly damaged,and the lung injury scores(0.21±0.22 vs 2.98±0.46)and lung wet/dry weight ratios(3.09±0.41 vs 6.36±0.61)were significantly increased(P<0.01).Compared with model group,the lung injury scores(1.80±0.31 and 1.05±0.25 vs 2.98±0.46)and lung wet/dry weight ratios(5.25±0.44 and 3.89±0.35 vs 6.36±0.61)in low-and high-dose SPJ IVa groups were significantly reduced(P<0.01).The administration of LPS resulted in elevated levels of pro-inflammatory cy-tokines(IL-1β,IL-6,and TNF-α)as well as the oxidative marker MDA in both serum and BALF(P<0.01).Additional-ly,it led to a decrease in antioxidant markers SOD and GSH(P<0.01).However,treatment with both low and high doses of SPJ IVa effectively attenuated the LPS-induced production of pro-inflammatory factors and oxidative markers MDA(P<0.01),while also increasing SOD and GSH levels(P<0.05 or P<0.01).In the model group,evident apoptosis was ob-served in lung tissues,whereas treatment with low and high doses of SPJ IVa significantly suppressed TUNEL-positive cells and the expression of cleaved caspase-3(P<0.01).The expression levels of Nrf2,HO-1,NF-κB p65,and TLR4 in lung tissues were significantly higher in the model group than in the control group(P<0.01);in turn,after treatment with low and high doses of SPJ IVa,Nrf2 and HO-1 were further upregulated(P<0.01),whereas NF-κB p65 and TLR4 were downregulated(P<0.01).CONCLUSION:The inhibitory effect of SPJ IVa on LPS-induced ALI in rats may be attribut-ed to its ability to suppress the TLR4/NF-κB-and Nrf2/HO-1-mediated inflammatory response and oxidative stress.