Review: Mechanism, effectiveness, and the prospects of medicinal plants and their bioactive compounds in lowering ruminants' enteric methane emission.

Animal nutritionists continue to investigate new strategies to combat the challenge of methane emissions from ruminants. Medicinal plants (MPs) are known to be beneficial to animal health and exert functional roles in livestock due to their phytogenic compounds with antimicrobial, immunostimulatory, antioxidative, and anti-inflammatory activities. Some MP has been reported to be anti-methanogenic and can effectively lower ruminants' enteric methane emissions. This review overviews trends in MP utilization in ruminants, their bioactivity and their effectiveness in lowering enteric methane production. It highlights the MP regulatory mechanism and the gaps that must be critically addressed to improve its efficacy. MP could reduce enteric methane production by up to 8-50% by regulating the rumen fermentation pathway, directing hydrogen toward propionogenesis, and modifying rumen diversity, structure, and population of the methanogens and protozoa. Yet, factors such as palatability, extraction techniques, and economic implications must be further considered to exploit their potential fully.

[Thinking on ideological and political education in Medical Parasitology teaching].

With the deepening reform of ideological and political education, Medical Parasitology teaching needs to update the teaching concept, change the teaching ideas, as well as keep trying to combine ideological and political education with the curriculum content closely. In addition to teaching students' basic knowledge and practical skills, teachers are needed to cultivate their moral literacy and political awareness through course teaching, so as to provide the basis for students' subsequent adaptations to social environments and jobs. Currently, the study of ideological and political education in Medical Parasitology teaching is still in the exploratory stage. Therefore, colleges and universities need to carry out effective construction of ideological and political education in Medical Parasitology teaching, in order to achieve good teaching outcomes and provide insights into ideological and political education in teaching.

Heralded Three-Photon Entanglement from a Single-Photon Source on a Photonic Chip.

In the quest to build general-purpose photonic quantum computers, fusion-based quantum computation has risen to prominence as a promising strategy. This model allows a ballistic construction of large cluster states which are universal for quantum computation, in a scalable and loss-tolerant way without feed forward, by fusing many small n-photon entangled resource states. However, a key obstacle to this architecture lies in efficiently generating the required essential resource states on photonic chips. One such critical seed state that has not yet been achieved is the heralded three-photon Greenberger-Horne-Zeilinger (3-GHZ) state. Here, we address this elementary resource gap, by reporting the first experimental realization of a heralded 3-GHZ state. Our implementation employs a low-loss and fully programmable photonic chip that manipulates six indistinguishable single photons of wavelengths in the telecommunication regime. Conditional on the heralding detection, we obtain the desired 3-GHZ state with a fidelity 0.573±0.024. Our Letter marks an important step for the future fault-tolerant photonic quantum computing, leading to the acceleration of building a large-scale optical quantum computer.

[Expression and prognostic significance of KAP1 gene in malignant pleural mesothelioma].

Objective: To explore the expression of KAP1 (KRAB-associated protein 1, KAP1) in Malignant pleural mesothelioma (MPM) based on the cancer genome atlas (TCGA) and clinical trials. And elucidate the correlation between the expression of KAP1 and the clinical pathological parameters of patients with MPM and its prognosis. Methods: In April 2022, Based on the second generation KAP1mRNA sequencing data and clinicopathological data of MPM patients downloaded from TCGA database, the correlation between KAP1mRNA expression and clinical parameters was analyzed, and the correlation between KAP1 protein expression and clinicopathological parameters and its prognostic value were analyzed based on Chuxiong data set cohort clinical samples. The expression of KAP1 mRNA in MPM samples and matched normal tumor adjacent tissues was detected by qRT-PCR, and the expression of KAP1 protein in MPM and normal pleural tissues was detected by immunohistochemistry and Westernblotting. To construct a Kaplan-Meier model to explore the effect of KAP1 expression on the prognosis of MPM patients, and to analyze the prognostic factors of MPM patients by Cox regression. Results: qRT-PCR and Western blotting detection showed that the expression levels of KAP1 gene in four different MPM cells (NCI-H28, NCI-H2052, NCI-H2452, and MTSO-211H) were significantly higher than those in normal pleural mesothelial cells Met-5A. qRT-PCR, Western blotting and IHC results demonstrated that the mRNA and protein expression levels of KAP1 in MPM tissues was significantly higher than that in matching normal mesothelial tissues, and the expression level of KAP1 protein was correlated with TP 53 protein expression levels and serum CEA levels (P<0.05) . The mRNA expression level was significantly correlated with the prognosis, The overall survival time of mesothelioma patients with high KAP1mRNA expression was significantly shorter (HR=3.7, Logrank P<0.001) . Tumor type, age and the mRNA expression were related to the prognosis of MPM patients (P<0.05) . Multivariate analysis showed that tumor type and KAP1 mRNA expression level were independent prognostic factors of MPM patients (P<0.05) . Conclusion: In this study, TCGA database and Chuxiong cohort experiment samples were used to collect the relevant information of KAP1 expression in malignant melanoma tissues. It was confirmed that KAP1 is highly expressed in MPM tissues. The mRNA expression level and pathological type are correlated with the prognosis of patients.

[Parecoxib sodium down-regulates CXCL8-CXCR1/2 to improve inflammatory microenvironment and promote patient recovery following laparoscopic radical resection of rectal cancer].

OBJECTIVE: To study the effect of parecoxib sodium on tumor microenvironment in patients undergoing laparoscopic radical resection of rectal cancer. METHODS: Sixty patients undergoing laparoscopic surgery for radical rectal cancer resection were randomized into test group and control group (n=30). The patients in test control group received intravenous injections of 40 mg parecoxib sodium at the time of anesthesia induction, immediately after and at 12 h after the surgery, and those in the control group were injected with an equal volume of physiological saline at the same time points. Plasma levels of IL-6, TNF-α, and CXCL8 of the patients were measured using ELISA, and expressions of CXCL8, CXCR1, and CXCR2 in the peripheral blood mononuclear cells (PBMCs) were detected with Western blotting. Postoperative VAS scores and gastrointestinal reactions and disease regression at 6 months after the operation were recorded. RESULTS: Compared with the control patients, the patients in the test group showed significantly reduced plasma levels of IL-6, TNF-α, and CXCL8 (P < 0.05) and milder elevations of CXCL8, CXCR1, and CXCR2 proteins in PBMCs (P < 0.05) with significantly lower VAS scores at 12 h and 24 h after the operation (P < 0.05) and lower postoperative incidence of adverse gastrointestinal reactions (P < 0.05). At 6 months after the operation, the number of patients with metastasis or tumor recurrence was significantly smaller in the test group than in the control group (P>0.05). CONCLUSION: Parecoxib sodium can improve the inflammatory microenvironment to promote patient recovery after laparoscopic radical resection of rectal cancer possibly through a mechanism that down-regulates CXCL8-CXCR1/2 expressions in the PBMCs.

[Multicenter retrospect analysis of early clinical features and analysis of risk factors on prognosis of elderly patients with severe burns].

Objective: To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis. Methods: This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results: Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions: The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

[Different methods in predicting mortality of pediatric intensive care units sepsis in Southwest China].

Objective: To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China. Methods: This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis. Results: Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) (Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS (Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion: Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

[Efficacy and safety of first-line treatment with anti-CD38 monoclonal antibody-based regimen for primary plasma cell leukemia].

Objective: To analyze the efficacy and safety of first-line treatment with an anti-CD38 monoclonal antibody regimen for primary plasma cell leukemia (pPCL). Methods: Patients diagnosed with pPCL from December 1st, 2018 to July 26th, 2023, receiving first-line treatment of anti-CD38 monoclonal antibody-based regimens across multiple centers including Peking University People's Hospital, Fuxing Hospital of Capital Medical University, Qingdao Municipal Hospital, Shengjing Hospital of China Medical University, Handan Central Hospital, the First Affiliated Hospital of Harbin Medical University, the Fourth Hospital of Hebei Medical University and General Hospital of Ningxia Medical University were consecutively included. A total of 24 pPCL patients were included with thirteen being male and eleven being female. The median age [M(Q1, Q3)] was 60 (57, 70) years. Patients were grouped according to peripheral blood plasma cell (PBPC) percentage [5%-19% (n=14) vs ≥20% (n=10)]. Last follow-up date was September 26th, 2023. The median follow-up period was 9.1 (4.2, 15.5) months. Patients' data related with clinical baseline characteristics, efficacy, survival and safety were retrospectively collected. Cox proportional hazards regression model was used to analyze risk factors associated with survival. Results: Among 24 pPCL patients, 16 (66.7%) patients had anemia at diagnosis, 13(54.2%) patients had thrombocytopenia, 8 (33.3%) patients had a baseline estimated glomerular filtration rate (eGFR)<40 ml·min-1·(1.73m2)-1, 13 (54.2%) patients had elevated lactate dehydrogenase (LDH) levels. The median PBPC percentage was 16% (8%, 26%) . Fluorescence in situ hybridization testing indicated that patients harboring 17p deletion, t(4;14) or t(14;16) were 6 (25.0%), 4 (16.7%) and 4 (16.7%), respectively. The overall response rate was 83.3% (20/24). The median progression-free survival (PFS) was 20.5 (95%CI: 15.8-25.2) months, and the median overall survival (OS) was not reached. Estimated 1-year and 2-year PFS and OS rates were 75.0% and 89.1%, 37.5% and 53.4%, respectively. The median PFS and OS for patients with PBPC percentages 5%-19% and≥20% were not reached and 20.5 (95%CI:15.7-25.3) months, 17.8 months and not reached, respectively. There was no significant statistical difference of PFS and OS between two groups (all P>0.05). Multivariate Cox regression analysis showed that 1p32 deletion was the risk factor associated with PFS (HR=7.7, 95%CI: 1.1-54.9, P=0.043). Seventeen patients (70.8%) developed grade 3-4 hematologic toxicities. Twelve patients (50.0%) developed grade 3-4 thrombocytopenia. Sixteen patients (66.7%) developed infection. All hematologic toxicities and infections were improved after supportive treatment. Conclusion: First-line treatment with anti-CD38 monoclonal antibody-based therapy for pPCL is effective and safe.

Delphi consensus statement for understanding and managing the subcostal hernia: subcostal hernias collaborative report (scholar study).

INTRODUCTION: Subcostal hernias are categorized as L1 based on the European Hernia Society (EHS) classification and frequently involve M1, M2, and L2 sites. These are common after hepatopancreatic and biliary surgeries. The literature on subcostal hernias mostly comprises of retrospective reviews of small heterogenous cohorts, unsurprisingly leading to no consensus or guidelines. Given the limited literature and lack of consensus or guidelines for dealing with these hernias, we planned for a Delphi consensus to aid in decision making to repair subcostal hernias. METHODS: We adopted a modified Delphi technique to establish consensus regarding the definition, characteristics, and surgical aspects of managing subcostal hernias (SCH). It was a four-phase Delphi study reflecting the widely accepted model, consisting of: 1. Creating a query. 2. Building an expert panel. 3. Executing the Delphi rounds. 4. Analysing, presenting, and reporting the Delphi results. More than 70% of agreement was defined as a consensus statement. RESULTS: The 22 experts who agreed to participate in this Delphi process for Subcostal Hernias (SCH) comprised 7 UK surgeons, 6 mainland European surgeons, 4 Indians, 3 from the USA, and 2 from Southeast Asia. This Delphi study on subcostal hernias achieved consensus on the following areas-use of mesh in elective cases; the retromuscular position with strong discouragement for onlay mesh; use of macroporous medium-weight polypropylene mesh; use of the subcostal incision over midline incision if there is no previous midline incision; TAR over ACST; defect closure where MAS is used; transverse suturing over vertical suturing for closure of circular defects; and use of peritoneal flap when necessary. CONCLUSION: This Delphi consensus defines subcostal hernias and gives insight into the consensus for incision, dissection plane, mesh placement, mesh type, and mesh fixation for these hernias.

[Evaluation of the efficacy of urine-based lipoarabinomannan antigen test in the diagnosis of pulmonary tuberculosis].

Objective: To analyze the diagnostic efficacy of urinary lipoarabinomannan (LAM) antigen detection method in tuberculosis patients, and to provide an experimental basis for the clinical application of urinary LAM kit in China. Methods: From March to May 2023, 228 patients with lung diseases [134 male, 94 female, age 20-82 (44.8±16.7) years] were prospectively collected in Beijing Chest Hospital, Capital Medical University, including 143 pulmonary tuberculosis patients and 85 non-tuberculosis patients. Urine and sputum samples from patients were collected for traditional etiological detection and urinary LAM antigen detection. The screening results of each positive detection combination were analyzed, and the difference analysis and regression analysis were performed. Results: The detection sensitivity and specificity of the urinary LAM kit were 46.2% (95%CI: 37.9%-54.7%) and 96.5% (95%CI: 89.3%-99.1%), respectively, with an overall coincidence rate of 64.9%. The detection rate of LAM antigen detection and GeneXpert MTB/RIF (Xpert) combined (60.8%, 87/143) was significantly higher than that of Xpert alone (49.7%, 71/143), and the difference was statistically significant (P<0.05). The results of risk factor analysis showed that the risk of negative urinary LAM antigen test results increased significantly as the bacterial load decreased. Conclusions: Urine LAM antigen detection method has a high specificity and can be combined with traditional methods to effectively improve the detection rate. Urinary LAM antigen detection method still has limitations, such as the influence of bacterial load and the inability to distinguish nontuberculosis mycobacteria samples, which needs further experimental verification.

The relationship and diagnostic efficacy of N-terminal propeptide type III collagen in pathological changes associated with non-alcoholic steatohepatitis.

OBJECTIVE: This study delves into the role of N-terminal propeptide type III collagen (PIIINP) in the diagnosis and management of liver pathological changes associated with non-alcoholic steatohepatitis (NASH). PATIENTS AND METHODS: We collected baseline information, pathological data, and serum PIIINP levels of 168 patients diagnosed with non-alcoholic fatty liver disease (NAFLD) via ultrasound imaging in our hospital. Based on the non-alcoholic fatty liver disease activity score (NAS), patients with different NAFLD patterns were divided into a Definite NASH group and a Not/borderline group. Differences in PIIINP levels and pathological features between the two groups were compared and analyzed. The diagnostic value of PIIINP for NASH was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: Patients with NASH exhibited significantly higher values of homeostatic model assessment for insulin resistance (HOMA-IR), fibrosis biomarker fibrosis-4 (FIB-4), aminotransferase-to-platelet ratio index (APRI), and serum PIIINP levels than those classified as Not/borderline. A marked increase in the serum concentrations of PIIINP was observed with the severity of fatty degeneration, lobular inflammation, and hepatocellular ballooning. The AUC of PIIINP for diagnosing definite NASH was 0.766 (95% CI: 0.694, 0.839), APRI was 0.634 (95% CI: 0.549, 0.718), and FIB-4 was 0.621 (95% CI: 0.534, 0.708). The AUC of PIIINP for diagnosing definite NASH was significantly higher than that of APRI and FIB-4 (all p<0.05). Utilizing the predetermined threshold values for diagnostic parameters, the PIIINP measure demonstrated a sensitivity of 71.6% and a specificity of 73.6% in diagnosing definitive NASH when its value exceeded 7.72 ng/dL. This yielded a Youden index of 0.45. Similarly, when the APRI measure exceeded 0.21, it exhibited a sensitivity of 60.5% and a specificity of 63.2%, resulting in a Youden index of 0.24. Moreover, when the FIB-4 index surpassed 0.26, it showed a sensitivity of 46.9% and a specificity of 79.3%, culminating in a Youden index of 0.26. CONCLUSIONS: NASH patients in this study exhibited significantly elevated PIIINP serum levels, which were closely associated with hepatocyte pathological changes. PIIINP demonstrated superior competence in diagnosing NASH than APRI and FIB-4 and thus offers a viable alternative for the clinical diagnosis of NASH.

Association of anatomical features of the petrotympanic fissure and presence of foramen of Huschke with otalgia and tinnitus.

The petrotympanic fissure (PTF) and foramen of Huschke (FH) are anatomical structures in the temporal bone that can connect the temporomandibular joint (TMJ) and the ear. The purpose of this retrospective study was to investigate the association between PTF morphology and otalgia and tinnitus, as well as the prevalence of the FH and otological symptoms, using cone beam computed tomography (CBCT). CBCT images from 114 patients presenting with symptoms of a temporomandibular disorder were examined retrospectively. The PTF was classified into three subtypes (open, semi-open, closed) and the presence of the FH was identified. Symptoms of otalgia and tinnitus were obtained from the patient files. The FH was observed in 12.3% of patients examined, and in 12.0% of those with otalgia and 18.9% of those with tinnitus. There was no significant association between the PTF subtypes or the presence of the FH and otalgia or tinnitus (all P > 0.05). The PTF subtype and presence of the FH alone do not appear to contribute to otalgia or tinnitus in patients with temporomandibular disorders.

[Alteration and significance of serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma: a retrospective study based on LEGEND-2].

Objective: To explore the dynamic changes in serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma (R/R MM) based on LEGEND-2. Methods: The data of patients with R/R MM who underwent BCMA-CAR-T therapy at our hospital between March 30, 2016, and February 6, 2018, were retrospectively collected. Serum lipid levels, controlled nutritional status (CONUT) score, and other clinical indicators at different time points before and after CAR-T-cell infusion were compared and analyzed. The best cut-off value was determined by using the receiver operator characteristic (ROC) curve. The patients were divided into high-CONUT score (>6.5 points, malnutrition group) and low-CONUT score groups (≤6.5 points, good nutrition group), comparing the progression-free survival (PFS) and total survival (OS) of the two groups using Kaplan-Meier survival analysis. Results: Before the infusion of CAR-T-cells, excluding triglycerides (TG), patients' serum lipid levels were lower than normal on average. At 8-14 d after CAR-T-cell infusion, serum albumin (ALB), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and apolipoprotein A1 (Apo A1) levels dropped to the minimum, whereas CONUT scores reached the maximum. In addition to TG, apolipoprotein B (Apo B) levels increased compared with baseline. After CAR-T-cell therapy, the patients' serum lipid levels significantly increased with well-improved nutritional status. Spearman's related analysis showed that TC, HDL, and ApoA1 levels after CAR-T-cell injection were significantly negatively correlated with the grade of cytokine-release syndrome (CRS) (r=-0.548, P=0.003; r=-0.444, P=0.020; r=-0.589, P=0.001). Furthermore, survival analysis indicated that the CONUT score was unrelated to PFS, and the median OS of patients with R/R MM in the high-CONUT score group was shorter than that in the low-CONUT score group (P=0.046) . Conclusions: During CAR-T-cell therapy, hypolipidemia and poor nutritional status were aggravated, which is possibly related to CRS. The patients' serum lipid levels and nutritional status were significantly improved after CAR-T-cell treatment. The CONUT score affected the median OS in patients treated with CAR-T-cells. Therefore, specific screening and intervention for nutritional status in patients receiving CAR-T-cell therapy are required.

Alcohol dehydrogenase-1B represses the proliferation, invasion and migration of breast cancer cells by inactivating the mitogen-activated protein kinase signalling pathway.

Breast cancer (BRCA) is a serious life-threatening cancer, especially triple-negative breast cancer (TNBC). Alcohol dehydrogenase-1B (ADH1B) has recently been revealed to be associated with poor prognosis of BRCA patients. This study identified the exact function of ADH1B on the progression of BRCA and TNBC. ADH1B effect on the prognosis of BRCA and TNBC patients was researched based on online databases and clinical samples. The function of ADH1B on the proliferation, invasion and migration, and growth of BRCA and TNBC cells was investigated by cell counting kit-8, Transwell, and in vivo assays. Western blot was utilized to determine the effect of ADH1B on the mitogen-activated protein kinase (MAPK) signalling pathway activity. As a result, ADH1B was down-regulated in BRCA and TNBC patients and cells, predicting unfavorable prognosis (P<0.05). ADH1B overexpression suppressed the proliferation, invasion and migration, and inactivated the MAPK signalling pathway in BRCA and TNBC cells (P<0.01). ADH1B synergized with Selumetinib (inhibitor of the MAPK signalling pathway) to attenuate the proliferation, invasion and migration of BRCA and TNBC cells (P<0.001). Conversely, Vacquinol-1 (activator of the MAPK signalling pathway) abolished the suppression of ADH1B on the proliferation, invasion and migration of BRCA and TNBC cells (P<0.05). ADH1B suppressed in vivo growth of TNBC cells (P<0.001). Thus, ADH1B may inhibit the proliferation, invasion and migration of BRCA and TNBC cells by inactivating the MAPK signalling pathway. It may be a promising target for the clinical treatment of BRCA and TNBC.

[Treatment of anterior megalophthalmos cataract with reverse optic capture intraocular lens implantation: a case report].

A 56-year-old male patient sought medical attention due to a gradual decline in bilateral visual acuity, which had been ongoing for a year and had rapidly worsened over the past three months. He received an initial diagnosis of bilateral concurrent cataracts and bilateral anterior megalophthalmos. Subsequently, cataract removal surgery was performed. During the surgery, it was observed that the patient had lax and fragile zonules of the crystalline lens. To address this issue, the surgical team employed reverse optic capture technique for the implantation of a three-piece intraocular lens. Following the surgery, the patient experienced a substantial improvement in uncorrected visual acuity. Remarkably, the patient remained free from adverse reactions, such as elevated intraocular pressure, during a follow-up period extending to 11 years.

[Sevoflurane alleviates ventilator-induced lung injury in rats by down-regulating the TRPV4/C-PLA2 signaling pathway].

OBJECTIVE: To explore the mechanism underlying the protective effect of sevoflurane against ventilator-induced lung injury (VILI). METHODS: Thirty-two SD rats were randomized into mechanical ventilation (MV) group, MV+sevoflurane group (MS group), MV+sevoflurane+transient receptor potential vanillate subtype 4 (TRPV4) agonist group (MST group) and MV+ sevoflurane + vehicle group (MSV group). Arachidonic acid (AA) in the lung tissues was quantified with ELISA. TRPV4, cytoplasmic phospholipase A2 (C-PLA2) and myosin light chain kinase (MLCK) protein expressions were detected by Western blotting. Lung injury in the rats was evaluated by assessing MLCK protein expression level, pulmonary permeability index, lung wet/dry ratio, leukocyte count in the bronchoalveolar lavage fluid (BALF), myeloperoxidase content in lung tissue, and histological score of the lungs. RESULTS: The rats in MV group showed significantly increased TRPV4 and C-PLA2 expression levels in the lung tissues with increased lung permeability and obvious lung inflammation compared with those in the other 3 groups (P < 0.05). No significant differences were found in the parameters associated with lung injuries between MS group and MSV group. Compared with those in MST group, the rats in MS group and MSV group showed significantly reduced AA production and TRPV4 and C-PLA2 expressions in the lungs (P < 0.05) with alleviated lung hyper-permeability and inflammation (P < 0.05). CONCLUSION: Sevoflurane protects against VILI in rats by down-regulating the TRPV4/C-PLA2 signaling pathway.

[The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study].

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

Investigating the prognostic value of constructing disulfidptosis-related gene models for lung adenocarcinoma patients.

OBJECTIVE: Disulfidptosis is a novel mode of cell death, a programmed mode of intracellular disulfide accumulation due to solute carrier family 7 member 11 (SLC7A11)-mediated abnormalities in the cell membrane cystine transport system. Numerous studies have confirmed the prominent role played by SLC7A11 in tumors, but the involvement of SLC7A11 as an important mediator of disulfidptosis in the death process of lung adenocarcinoma cells remains unclear. MATERIALS AND METHODS: We obtained 4,107 SLC7A11-related genes and analyzed them using a total of 1,040 lung adenocarcinoma transcriptome sequencing data from The Cancer Genome Atlas (TCGA) cohort and GEO (Gene Expression Omnibus) cohort and 991 relevant clinical data. First, we screened for differential genes and identified molecular subtypes for assessing characteristic differences between lung adenocarcinoma subtypes under the influence of SLC7A11-associated genes. Then, risk score models were constructed to assess the prognosis, immune infiltration, tumor microenvironment, and drug treatment effects in lung adenocarcinoma patients. Finally, we also analyzed the distribution of cell types and expression of characteristic genes within the tumor using a single-cell database. In addition, relevant drug sensitivities were predicted. RESULTS: We screened 956 genes with significant differences and identified 2 molecular subtypes and found significant differences in their prognosis and that subtype B had a significantly better survival prognosis than subtype A. In addition, we found that pathways associated with cell proliferation division and DNA repair were enriched in the high-risk type A samples. Finally, we constructed a robust risk-scoring system, and our risk analysis revealed a general reduction of various immune cell components and tumor stromal components in the immune microenvironment of high-risk lung adenocarcinoma and a distinct immune infiltration pattern of immune cells, which was associated with a lower survival rate. CONCLUSIONS: Our comprehensive analysis of SLC7A11-related genes suggests that disulfidptosis has a potential value in the tumor microenvironment, immunity, clinical outcome, and prognosis of lung adenocarcinoma. These findings may increase our understanding of disulfidptosis as a novel cell death paradigm and provide ideas for assessing the prognosis of lung adenocarcinoma and developing new diagnostic and therapeutic strategies.

[GPR109A partly mediates inhibitory effects of ß-hydroxybutyric acid on lung adenocarcinoma cell proliferation, migration and invasion].

OBJECTIVE: To explore the mechanism that mediates the inhibitory effects of ß-hydroxybutyrate (BHB) on lung adenocarcinoma cells. METHODS: A549 and LLC cell lines treated with 5 or 10 mmol/L BHB were examined for changes in cell viability, proliferation, migration, and invasion using CCK-8 assay, EdU staining, scratch assay, and Transwell assay. The differential expression of GPR109A in lung adenocarcinoma and normal lung tissue was analyzed using GEPIA database. GPR109A expressions in BHB-treated lung adenocarcinoma cells were determined using RT-PCR and Western blotting. The changes in IC50 of BHB were examined in A549 and LLC cells with GPR109A knockdown. The effect of BHB administered via gavage for 21 days on tumor growth was evaluated in nude mouse and Balb/c mouse models bearing xenografts derived A549 and LLC cells with or without GPR109A knockdown. RESULTS: Treatment with BHB concentration-dependently repressed the viability, proliferation, migration and invasion of A549 and LLC cells. GPR109A expression was significantly decreased in lung adenocarcinoma tissues and A549 and LLC cell lines (P<0.05). Loss of function experiments showed that the inhibitory effects of BHB on A549 and LLC cells were partly mediated by GPR109A, and in the tumor-bearing mouse models, BHB significantly inhibited tumor growth partly by regulating GPR109A expression (P<0.05). CONCLUSION: BHB can repress the malignant behaviors of A549 and LLC cells and inhibit tumor growth in mice, and these effects are mediated partly by regulating GPR109A expression.

[A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors].

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.