Bazi Bushen alleviates reproductive aging in aged male mice.

Bazi Bushen (BZBS), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy in testicular dysfunction within D-galactose and NaNO2 mouse models. This study aimed to ascertain if BZBS could also mitigate the decline in testicular function associated with natural aging. Therefore, male aged mice were employed to evaluate the preventive effects of BZBS on male reproductive aging. This was achieved by assessing sex hormone production, testicular histomorphology, and spermatogenesis. Relative to the untreated aged control group, BZBS administration elevated the levels of sex hormones and spermatocyte populations and preserved normal testicular structure in aged mice. Notably, spermatogenesis was maintained. Further analyses, including malondialdehyde (MDA) assays and real-time PCR, indicated that BZBS diminished testicular oxidative stress and the inflammatory burden. Corroborating these findings, mice treated with BZBS exhibited reductions in the populations of senescent and apoptotic cells within the seminiferous tubules, suggesting alleviated cellular damage. In contrast, we observed that rapamycin, a drug known for its longevity benefits, induced excessive testicular apoptosis and did not decrease lipid peroxidation. Collectively, our results highlight BZBS's promising clinical potential in counteracting male reproductive aging, underlining its mechanisms of action.

A Multimode Optical Sensor for Selective and Sensitive Detection of Harmful Heavy Metal Cr(VI) in Fresh Water and Sea Water.

Water pollution originating from heavy metals has shown great impacts on the ecological environment and human health due to their extremely low biodegradability. Hexavalent chromium Cr(VI), as one harmful heavy metal with strong oxidation, high biological permeability, and high carcinogenicity, is becoming an increasingly serious threat to human health. Therefore, conveniently but accurately, monitoring the Cr(VI) level in water to maintain its normal level and ensuring the stability of the ecosystem and human health become very valuable. However, most of these heavy metal sensors reported are turn-off type single-emission sensors. In this work, a ratiometric fluorescence/colorimetry/smartphone triple-mode turn-on optical sensor for Cr(VI) was developed based on a multifunctional metal-organic framework platform. The detection limits for these three mutual verification modes were only 1.28, 4.89, and 68.4 nM, respectively. Additionally, the color changes of the detection system under sunlight can also be observed directly by the naked eye. The accuracy and practicability of this multimode sensor were further proved by the detection of Cr(VI) in actual water and seawater samples, and the recovery rate ranged from 97.308 to 104.041%.

Super enhancer-associated circRNA-circLrch3 regulates hypoxia-induced pulmonary arterial smooth muscle cells pyroptosis by formation of R-loop with host gene.

BACKGROUND: Pulmonary hypertension (PH) is a complex vascular disorder, characterized by pulmonary vessel remodeling and perivascular inflammation. Pulmonary arterial smooth muscle cells (PASMCs) pyroptosis is a novel pathological mechanism implicated of pulmonary vessel remodeling. However, the involvement of circRNAs in the process of pyroptosis and the underlying regulatory mechanisms remain inadequately understood. METHODS: Western blotting, PI staining and LDH release were used to explore the role of circLrch3 in PASMCs pyroptosis. Moreover, S9.6 dot blot and DRIP-PCR were used to assess the formation of R-loop between circLrch3 and its host gene Lrch3. Chip-qPCR were used to evaluate the mechanism of super enhancer-associated circLrh3, which is transcriptionally activated by the transcription factor Tbx2. RESULTS: CircLrch3 was markedly upregulated in hypoxic PASMCs. CircLrch3 knockdown inhibited hypoxia induced PASMCs pyroptosis in vivo and in vitro. Mechanistically, circLrch3 can form R-loop with host gene to upregulate the protein and mRNA expression of Lrch3. Furthermore, super enhancer interacted with the Tbx2 at the Lrch3 promoter locus, mediating the augmented transcription of circLrch3. CONCLUSION: Our findings clarify the role of a super enhancer-associated circLrch3 in the formation of R-loop with the host gene Lrch3 to modulate pyroptosis in PASMCs, ultimately promoting the development of PH.

Biological Control of a Root-Knot Nematode Meloidogyne incognita Infection of Tomato (Solanum lycopersicum L.) by the Oomycete Biocontrol Agent Pythium oligandrum.

The biocontrol agent Pythium oligandrum, which is a member of the phylum Oomycota, can control diseases caused by a taxonomically wide range of plant pathogens, including fungi, bacteria, and oomycetes. However, whether P. oligandrum could control diseases caused by plant root-knot nematodes (RKNs) was unknown. We investigated a recently isolated P. oligandrum strain GAQ1, and the P. oligandrum strain CBS530.74, for the control of an RKN Meloidogyne incognita infection of tomato (Solanum lycopersicum L.). Initially, P. oligandrum culture filtrates were found to be lethal to M. incognita second-stage juveniles (J2s) with up to 84% mortality 24 h after treatment compared to 14% in the control group. Consistent with the lethality to M. incognita J2s, tomato roots treated with P. oligandrum culture filtrates reduced their attraction of nematodes, and the number of nematodes penetrating the roots was reduced by up to 78%. In a greenhouse pot trial, the P. oligandrum GAQ1 inoculation of tomato plants significantly reduced the gall number by 58% in plants infected with M. incognita. Notably, the P. oligandrum GAQ1 mycelial treatment significantly increased tomato plant height (by 36%), weight (by 27%), and root weight (by 48%). A transcriptome analysis of tomato seedling roots inoculated with the P. oligandrum GAQ1 strain identified ~2500 differentially expressed genes. The enriched GO terms and annotations in the up-regulated genes suggested a modulation of the plant hormone-signaling and defense-related pathways in response to P. oligandrum. In conclusion, our results support that P. oligandrum GAQ1 can serve as a potential biocontrol agent for M. incognita control in tomato. Multiple mechanisms appear to contribute to the biocontrol effect, including the direct inhibition of M. incognita, the potential priming of tomato plant defenses, and plant growth promotion.

Bazi Bushen ameliorates age-related energy metabolism dysregulation by targeting the IL-17/TNF inflammatory pathway associated with SASP.

BACKGROUND: Chronic inflammation and metabolic dysfunction are key features of systemic aging, closely associated with the development and progression of age-related metabolic diseases. Bazi Bushen (BZBS), a traditional Chinese medicine used to alleviate frailty, delays biological aging by modulating DNA methylation levels. However, the precise mechanism of its anti-aging effect remains unclear. In this study, we developed the Energy Expenditure Aging Index (EEAI) to estimate biological age. By integrating the EEAI with transcriptome analysis, we aimed to explore the impact of BZBS on age-related metabolic dysregulation and inflammation in naturally aging mice. METHODS: We conducted indirect calorimetry analysis on five groups of mice with different ages and utilized the data to construct EEAI. 12 -month-old C57BL/6 J mice were treated with BZBS or ß-Nicotinamide Mononucleotide (NMN) for 8 months. Micro-CT, Oil Red O staining, indirect calorimetry, RNA sequencing, bioinformatics analysis, and qRT-PCR were performed to investigate the regulatory effects of BZBS on energy metabolism, glycolipid metabolism, and inflammaging. RESULTS: The results revealed that BZBS treatment effectively reversed the age-related decline in energy expenditure and enhanced overall metabolism, as indicated by the aging index of energy expenditure derived from energy metabolism parameters across various ages. Subsequent investigations showed that BZBS reduced age-induced visceral fat accumulation and hepatic lipid droplet aggregation. Transcriptomic analysis of perirenal fat and liver indicated that BZBS effectively enhanced lipid metabolism pathways, such as the PPAR signaling pathway, fatty acid oxidation, and cholesterol metabolism, and improved glycolysis and mitochondrial respiration. Additionally, there was a significant improvement in inhibiting the inflammation-related arachidonic acid-linoleic acid metabolism pathway and restraining the IL-17 and TNF inflammatory pathways activated via senescence associated secretory phenotype (SASP). CONCLUSIONS: BZBS has the potential to alleviate inflammation in metabolic organs of naturally aged mice and maintain metabolic homeostasis. This study presents novel clinical therapeutic approaches for the prevention and treatment of age-related metabolic diseases.

Terpenoids derived from Semen Ziziphi Spinosae oil enhance sleep by modulating neurotransmitter signaling in mice.

Semen Ziziphi Spinosae oil (SZSO) is a natural vegetable oil extracted from Semen Ziziphi Spinosae, a traditional Chinese medicine renowned for its sleep-promoting properties, while the mechanisms are still unclear. Our findings revealed that the terpenoids present in SZSO (T-SZSO) were identified as the active components responsible for promoting sleep. Network pharmacological analysis suggested that T-SZSO targeted different sleep-aid pathways to varying degrees and exhibited potential for preventing central nervous system diseases. Notably, lupeol and betulinicaldehyde exhibited more pronounced effects. Additionally, T-SZSO significantly elevated serotonin levels, enhanced gamma-aminobutyric acid (GABA) synthesis, promoted GABA A receptor expression, and decreased glutamate and norepinephrine expression levels. Moreover, T-SZSO was found to downregulate IL-1ß expression while upregulating superoxide dismutase and inducible nitric oxide synthase levels. In conclusion, this study presents the first investigation into the pharmacological basis of SZSO in promoting sleep and highlights the potential of nature food in improving suboptimal health conditions.

AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies.

Aldo-Keto Reductase Family 1 Member C3 (AKR1C3), also known as type 5 17ß-hydroxysteroid dehydrogenase (17ß-HSD5) or prostaglandin F (PGF) synthase, functions as a pivotal enzyme in androgen biosynthesis. It catalyzes the conversion of weak androgens, estrone (a weak estrogen), and PGD2 into potent androgens (testosterone and 5α-dihydrotestosterone), 17ß-estradiol (a potent estrogen), and 11ß-PGF2α, respectively. Elevated levels of AKR1C3 activate androgen receptor (AR) signaling pathway, contributing to tumor recurrence and imparting resistance to cancer therapies. The overexpression of AKR1C3 serves as an oncogenic factor, promoting carcinoma cell proliferation, invasion, and metastasis, and is correlated with unfavorable prognosis and overall survival in carcinoma patients. Inhibiting AKR1C3 has demonstrated potent efficacy in suppressing tumor progression and overcoming treatment resistance. As a result, the development and design of AKR1C3 inhibitors have garnered increasing interest among researchers, with significant progress witnessed in recent years. Novel AKR1C3 inhibitors, including natural products and analogues of existing drugs designed based on their structures and frameworks, continue to be discovered and developed in laboratories worldwide. The AKR1C3 enzyme has emerged as a key player in carcinoma progression and therapeutic resistance, posing challenges in cancer treatment. This review aims to provide a comprehensive analysis of AKR1C3's role in carcinoma development, its implications in therapeutic resistance, and recent advancements in the development of AKR1C3 inhibitors for tumor therapies.

Existing hip joint disease is associated with an increased incidence of hip fracture in adults: A retrospective survey of 9710 individuals from a single center.

Objective: In hip disease patients, pain and movement restrictions might cause changes in bone strength and increase the likelihood of falls, finally leading to hip fracture. The aim of this study was to identify the incidence of, characteristics of and risk factors for hip fracture in patients with existing hip disease. Methods: This was a retrospective cohort study. Patients with existing hip disease treated at both outpatient and inpatient departments of our institute were identified by searching the electronic medical record system and followed retrospectively for the occurrence of hip fracture. Demographic and clinical characteristics, such as age, sex and kind of primary hip disease, were collected from the electronic medical record system. The incidence and timing of hip fracture were estimated, and a Cox regression model was built to identify the independent risk factors for hip fracture in these patients. Results: A total of 9710 eligible patients were included. After a mean follow-up of 3.97 years, hip fractures were identified in 95 patients, for an estimated incidence of hip fracture of 978.37 per 100,000 patients. The femoral neck was involved in 49 fractures (51.58 %), and the femoral trochanter was involved in 45 fractures (47.37 %). Four independent risk factors and one protective factor for hip fracture in patients with hip diseases were identified: age (HR = 1.116, 95 % CI = 1.094-1.138), the presence of osteonecrosis of the femoral head (HR = 2.201, 95 % CI = 1.217-3.980), a lower Harris hip score (HR = 0.966, 95 % CI = 0.949-0.982), a history of previous hip surgery (HR = 2.126, 95 % CI = 1.304-3.466) and the use of walking aids (HR = 0.588, 95 % CI = 0.354-0.975). A scoring system with a total score of 20 points was built, which included all of the above risk factors. The predictive scores for a low risk (estimated incidence of hip fracture ≤30 %), a moderate risk (estimated incidence of hip fracture 31 %-69 %), and a high risk (estimated incidence of hip fracture ≥70 %) of hip fracture were ≤8.5 points, 9.0-13.0 points and ≥13.5 points, respectively. Conclusion: The incidence of hip fracture in the special population of patients with existing hip disease was determined. Elderly patients, patients with a history of hip surgery, patients with osteonecrosis and patients with poor Harris hip scores were at increased risk of hip fracture. In patients with a predictive score greater than 9 points, indicating a moderate to high risk of hip fracture, the use of a walking aid might reduce the risk of hip fracture.

Angelica keiskei water extract Mitigates Age-Associated Physiological Decline in Mice.

OBJECTIVE: Angelica keiskei is a medicinal and edible plant that has been reported to possess potent antioxidant properties in several in vitro models, but its effectiveness on naturally aging organisms is still lacking. This study explores the antioxidant and health-promoting effects of Angelica keiskei in naturally aging mice. METHODS: We treated 48-week-old mice with Angelica keiskei water extract (AKWE) 30 days, and measured indicators related to aging and antioxidants. In addition, we conducted network pharmacology analysis, component-target molecular docking, real-time PCR, and MTS assays to investigate relevant factors. RESULTS: The results indicated that administration of AKWE to mice led to decrease blood glucose levels, improve muscle fiber structure, muscle strength, gait stability, and increase levels of glutathione and superoxide dismutase in serum. Additionally, it decreased pigmentation of the heart tissues. Angelica keiskei combats oxidative stress by regulating multiple redox signaling pathways, and its ingredients Coumarin and Flavonoids have the potential to bind to SIRT3 and SIRT5. CONCLUSIONS: Our findings indicated the potential of Angelica keiskei as a safe and effective dietary supplement to combat aging and revealed the broad prospects of medicinal and edible plants for addressing aging and age-related chronic diseases.

TRPA1-PI3K/Akt-OPA1-ferroptosis axis in ozone-induced bronchial epithelial cell and lung injury.

BACKGROUND: Transient receptor potential (TRP) ankyrin 1 (TRPA1) could mediate ozone-induced lung injury. Optic Atrophy 1 (OPA1) is one of the significant mitochondrial fusion proteins. Impaired mitochondrial fusion, resulting in mitochondrial dysfunction and ferroptosis, may drive the onset and progression of lung injury. In this study, we examined whether TRPA1 mediated ozone-induced bronchial epithelial cell and lung injury by activating PI3K/Akt with the involvement of OPA1, leading to ferroptosis. METHODS: Wild-type, TRPA1-knockout (KO) mice (C57BL/6 J background) and ferrostatin-1 (Fer-1)-pretreated mice were exposed to 2.5 ppm ozone for 3 h. Human bronchial epithelial (BEAS-2B) cells were treated with 1 ppm ozone for 3 h in the presence of TRPA1 inhibitor A967079 or TRPA1-knockdown (KD) as well as pharmacological modulators of PI3K/Akt-OPA1-ferroptosis. Transcriptome was used to screen and decipher the differential gene expressions and pathways. Oxidative stress, inflammation and ferroptosis were measured together with mitochondrial morphology, function and dynamics. RESULTS: Acute ozone exposure induced airway inflammation and airway hyperresponsiveness (AHR), reduced mitochondrial fusion, and enhanced ferroptosis in mice. Similarly, acute ozone exposure induced inflammatory responses, altered redox responses, abnormal mitochondrial structure and function, reduced mitochondrial fusion and enhanced ferroptosis in BEAS-2B cells. There were increased mitochondrial fusion, reduced inflammatory responses, decreased redox responses and ferroptosis in ozone-exposed TRPA1-KO mice and Fer-1-pretreated ozone-exposed mice. A967079 and TRPA1-KD enhanced OPA1 and prevented ferroptosis through the PI3K/Akt pathway in BEAS-2B cells. These in vitro results were further confirmed in pharmacological modulator experiments. CONCLUSION: Exposure to ozone induces mitochondrial dysfunction in human bronchial epithelial cells and mouse lungs by activating TRPA1, which results in ferroptosis mediated via a PI3K/Akt/OPA1 axis. This supports a potential role of TRPA1 blockade in preventing the deleterious effects of ozone.

Uric Acid Metabolic Disorders in Pituitary-Target Gland Axis.

Uric acid (UA) is the end product of purine metabolism in the human, and the imbalance between production and excretion results in the disturbance of serum uric acid (SUA). There is evidence suggesting that pituitary-target gland hormones can affect UA metabolism through regulating the activity of xanthine oxidase and UA transporters. Related endocrine diseases including thyroid dysfunction, polycystic ovary syndrome, acromegaly and Cushing's syndrome are often accompanied by elevated UA levels. In addition to the direct influence of abnormal hormones, obesity and insulin resistant play a pivotal role. Diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion also present with abnormal SUA levels due to the action of antidiuretic hormone. However, certain evidence within the population is disputed. This review summarized the effects of pituitary-target gland hormones on UA metabolism, and preliminarily described the related mechanisms, offering a theoretical foundation for assessing SUA in endocrine disorders as well as guiding its management.

Role of mitochondrial fusion proteins MFN2 and OPA1 on lung cellular senescence in chronic obstructive pulmonary disease.

BACKGROUND: Mitochondrial dysfunction and lung cellular senescence are significant features involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) stands as the primary contributing factor to COPD. This study examined mitochondrial dynamics, mitophagy and lung cellular senescence in COPD patients and investigated the effects of modulation of mitochondrial fusion [mitofusin2 (MFN2) and Optic atrophy 1 (OPA1)] on CS extract (CSE)-induced lung cellular senescence. METHODS: Senescence-associated secretory phenotype (SASP) component mRNAs (IL-1ß, IL-6, CXCL1 and CXCL8), mitochondrial morphology, mitophagy and mitochondria-related proteins (including phosphorylated-DRP1(p-DRP1), DRP1, MFF, MNF2, OPA1, PINK1, PARK2, SQSTM1/p62 and LC3b) and senescence-related proteins (including P16, H2A.X and Klotho) were measured in lung tissues or primary alveolar type II (ATII) cells of non-smokers, smokers and COPD patients. Alveolar epithelial (A549) cells were exposed to CSE with either pharmacologic inducer (leflunomide and BGP15) or genetic induction of MFN2 and OPA1 respectively. RESULTS: There were increases in mitochondrial number, and decreases in mitochondrial size and activity in lung tissues from COPD patients. SASP-related mRNAs, DRP1 phosphorylation, DRP1, MFF, PARK2, SQSTM1/p62, LC3B II/LC3B I, P16 and H2A.X protein levels were increased, while MFN2, OPA1, PINK1 and Klotho protein levels were decreased in lung tissues from COPD patients. Some similar results were identified in primary ATII cells of COPD patients. CSE induced increases in oxidative stress, SASP-related mRNAs, mitochondrial damage and dysfunction, mitophagy and cellular senescence in A549 cells, which were ameliorated by both pharmacological inducers and genetic overexpression of MFN2 and OPA1. CONCLUSIONS: Impaired mitochondrial fusion, enhanced mitophagy and lung cellular senescence are observed in the lung of COPD patients. Up-regulation of MFN2 and OPA1 attenuates oxidative stress, mitophagy and lung cellular senescence, offering potential innovative therapeutic targets for COPD therapy.

Acupuncture Treatment in a Mouse Model of Chronic Hypoxia-Induced Cognitive Dysfunction.

The treatment of central nervous disorders has consistently posed significant challenges to the medical field. Acupuncture, a non-pharmacological practice rooted in traditional Chinese medicine, entails the insertion of fine needles into precise points on the body and is commonly employed for the management of diverse conditions. Recently, acupuncture has emerged as a promising therapeutic intervention for a range of neurological diseases, including anxiety and respiratory disorders. However, the potential of acupuncture in treating cognitive dysfunction induced by chronic hypoxia has not yet been explored. This paper presents a comprehensive protocol for establishing a mouse model of chronic hypoxia-induced cognitive impairment, administering mild anesthesia, performing acupuncture treatment, and assessing behavioral changes and memory abilities using open field tests and water mazes. The step-by-step protocol provides detailed instructions on accurately locating and positioning acupoints and needles for cognitive improvement. By employing this protocol, researchers can conduct systematic studies to thoroughly evaluate the therapeutic potential of acupuncture for cognitive dysfunction.

Femoral neck fracture patients with ischaemic stroke choose hemiarthroplasty or constrained liner total hip arthroplasty? A retrospective comparative study of 199 cases.

Background: The objective of this study was to assess the long-term survival rate, complications, as well as the clinical and radiological outcomes of hemiarthroplasty and total hip arthroplasty using constrained polyethylene liners in patients with ischemic stroke. Methods: This study was a retrospective cohort study that included patients with ischemic stroke who underwent hip arthroplasty from March 2010 to September 2017. In the Constrained Acetabular Liners (CAL) group, patients received an uncemented acetabular shell with a constrained polyethylene liner. The Dual Mobility (DM) group underwent hemiarthroplasty (HA). Additionally, hip function, range of motion, quality of life, the incidence of clinical complications, and prosthesis stability were investigated. Results: 96 patients with unilateral femoral neck fractures who underwent hip replacement with CAL were included in the CAL group, while 103 patients who underwent hip replacement with a dual mobility head were included in the DM group. VAS, and SF-36 data were available for both CAL and DM groups. At the 1-year postoperative follow-up, the HHS in the CAL group was significantly lower than that in the DM group (80.83 ± 3.91 vs. 83.17 ± 4.15, P < 0.05). The VAS score in the CAL group peaked at the 1-year follow-up (2.07 ± 0.91 vs. 1.49 ± 0.85, P < 0.05). However, there were no significant differences between the two groups in terms of HSS, VAS, and SF-36 at the last follow-up after surgery. Operative time and the amount of bleeding in the DM group were significantly lower than those in the CAL group (105.30 ± 29.68 vs. 94.85 ± 31.07; 355.11 ± 123.95 vs. 302.22 ± 107.68, P < 0.05). Additionally, there was no significant difference in the mean leg length discrepancy between the two groups. Conclusion: The clinical, imaging, and postoperative complications of the CAL and DM groups were analyzed. The prognosis for DM appears to be more beneficial for early patient recovery, but a higher likelihood of recurrent dislocation is observed. CAL offers excellent stability for primary THA in high-risk patients; however, attention should be given to preventing aseptic loosening.

The effect of sodium-glucose cotransporter 2 inhibitors as an adjunct to insulin in patients with type 1 diabetes assessed by continuous glucose monitoring: A systematic review and meta-analysis.

AIMS: Patients undergoing insulin-based therapy for type 1 diabetes often experience poor glycemic control characterized by significant fluctuations. This study was undertaken to analyze the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2Is), as an adjunct to insulin, on time in range (TIR) and glycemic variability in patients with type 1 diabetes, using continuous glucose monitoring (CGM). In addition, we examined which type of SGLT2I yielded a superior effect compared to others. METHODS: We conducted a comprehensive search of PubMed, EMBASE, the Cochrane Library, Web of Science, and clinical trial registry websites, retrieving all eligible randomized clinical trials (RCTs) published up until February 2023. We analyzed the mean TIR, mean amplitude of glucose excursions (MAGE), mean daily glucose (MDG), diabetic ketoacidosis (DKA), standard deviation (SD), total insulin dose, and severe hypoglycemia to evaluate the efficacy and safety of SGLT2Is. A random-effects model was also employed. RESULTS: This study encompassed 15 RCTs. The meta-analysis revealed that the use of SGLT2Is as an adjuvant therapy to insulin led to a significant increase in TIR (MD = 10.78, 95%CI = 9.33-12.23, I2 = 42 %, P < 0.00001) and a decrease in SD (MD = -0.38, 95%CI = -0.50 to -0.26, I2 = 0 %, P < 0.00001), MAGE (MD = -0.92, 95%CI = -1.17 to -0.67, I2 = 19 %, P < 0.00001), MDG(MD = -1.01, 95%CI = -1.32 to -0.70, I2 = 48 %, P < 0.00001), and total insulin dose (MD = -5.81, 95%CI = -7.81 to -3.82, I2 = 32 %, P < 0.00001). No significant increase was observed in the rate of severe hypoglycemia (RR = 1.04, 95 % CI = 0.76-1.43, P = 0.80). However, SGLT2I therapy was associated with increased DKA occurrence (RR = 2.79, 95 % CI = 1.42-5.48; P = 0.003, I2 = 16 %). In addition, the subgroup analyses based on the type of SGLT2Is revealed that dapagliflozin might exhibit greater efficacy compared to other SGLT2Is across most outcomes. CONCLUSIONS: SGLT2Is exhibited a positive effect on improving blood glucose level fluctuations. Subgroup analysis showed that dapagliflozin appeared to have more advantages. However, giving due consideration to preventing adverse effects, particularly DKA, is paramount. REGISTRATION: Prospero CRD42023408276.

Unleashing the efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma: factors, strategies, and ongoing trials.

Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer, representing approximately 85% of cases. The diagnosis is often made in the middle and late stages, necessitating systemic treatment as the primary therapeutic option. Despite sorafenib being the established standard of care for advanced HCC in the past decade, the efficacy of systemic therapy remains unsatisfactory, highlighting the need for novel treatment modalities. Recent breakthroughs in immunotherapy have shown promise in HCC treatment, particularly with immune checkpoint inhibitors (ICIs). However, the response rate to ICIs is currently limited to approximately 15%-20% of HCC patients. Recently, ICIs demonstrated greater efficacy in "hot" tumors, highlighting the urgency to devise more effective approaches to transform "cold" tumors into "hot" tumors, thereby enhancing the therapeutic potential of ICIs. This review presented an updated summary of the factors influencing the effectiveness of immunotherapy in HCC treatment, identified potential combination therapies that may improve patient response rates to ICIs, and offered an overview of ongoing clinical trials focusing on ICI-based combination therapy.

A new joint reconstruction technique in the treatment of giant cell tumors around the knee: Structural allograft and unicompartmental arthroplasty.

OBJECTIVE: The long-term prognosis of patients who underwent unicompartmental knee arthroplasty (UKA) with a structural allograft or hemiarticular allograft transplantation to treat giant cell tumors (GCTs) around the knee and the prosthesis survival rate were analyzed. METHODS: We retrospectively reviewed 73 patients who were diagnosed with GCTs around the knee and underwent surgery to restore joint function from 2000 to 2015. Patients were divided into two groups according to the surgical procedure used for functional knee reconstruction: hemiarticular allograft transplantation or structural allograft and UKA. The Knee Society Score (KSS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used to analyze postoperative knee function between the two groups. The Kellgren-Lawrence (K-L) classification system was used to evaluate the progression of osteoarthritis. The incidence of complications and the prosthesis survival rate were also investigated. RESULTS: Patients who underwent UKA to treat GCT demonstrated significantly improved knee function. The rate of an excellent or good KSS was significantly different between the two groups (p = 0.041 at the 1-year follow-up, p = 0.033 at the last follow-up). The proportion of severe cases according to WOMAC in the two groups was also different (p = 0.030 at the 1-year follow-up, p = 0.021 at the last follow-up). According to the K-L grade of unaffected compartments, UKA better prevented the progression of osteoarthritis (p = 0.034). CONCLUSIONS: Patients with GCTs around the knee could benefit from UKA. In addition to providing better knee function and range of motion, UKA could also slow the progression of osteoarthritis in the knee joint. This new surgical method could meet the needs of patients wishing to preserve joint integrity and favorable joint function.

Attenuation of PM2.5-induced alveolar epithelial cells and lung injury through regulation of mitochondrial fission and fusion.

BACKGROUND: Exposure to particulate matter (PM) with an aerodynamic diameter less than 2.5 µm (PM2.5) is a risk factor for developing pulmonary diseases and the worsening of ongoing disease. Mitochondrial fission and fusion are essential processes underlying mitochondrial homeostasis in health and disease. We examined the role of mitochondrial fission and fusion in PM2.5-induced alveolar epithelial cell damage and lung injury. Key genes in these processes include dystrophin-related protein 1 (DRP1) and optic atrophy 1 (OPA1) respectively. METHODS: Alveolar epithelial (A549) cells were treated with PM2.5 (32 µg/ml) in the presence and absence of Mdivi-1 (10µM, a DRP1 inhibitor) or BGP-15 (10µM, an OPA1 activator). Results were validated using DRP1-knockdown (KD) and OPA1-overexpression (OE). Mice were injected intraperitoneally with Mdivi-1 (20 mg/kg), BGP-15 (20 mg/kg) or distilled water (control) one hour before intranasal instillation of PM2.5 (7.8 mg/kg) or distilled water for two consecutive days. RESULTS: PM2.5 exposure of A549 cells caused oxidative stress, enhanced inflammation, necroptosis, mitophagy and mitochondrial dysfunction indicated by abnormal mitochondrial morphology, decreased mitochondrial membrane potential (ΔΨm), reduced mitochondrial respiration and disrupted mitochondrial fission and fusion. Regulating mitochondrial fission and fusion pharmacologically using Mdivi-1 and BGP-15 and genetically using DRP1-KD and OPA1-OE prevented PM2.5-induced celluar damage in A549 cells. Mdivi-1 and BGP-15 attenuated PM2.5-induced acute lung injury in mice. CONCLUSION: Increased mitochondrial fission and decreased mitochondrial fusion may underlie PM2.5-induced alveolar epithelial cell damage in vitro and lung injury in vivo.

Changes in targeted metabolomics in lung tissue of chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a common chronic lung disease and its incidence is steadily increasing. COPD patients and mouse models of COPD share some similarities in lung pathology and physiology. We performed this study to explore the potential metabolic pathways involved in the pathogenesis of COPD and to discover the COPD-associated biomarkers. Furthermore, we aimed to examine how much the mouse model of COPD was similar and different to human COPD in terms of the altered metabolites and pathways. Methods: Twenty human lung tissue samples (ten COPD and ten controls) and twelve mice lung tissue samples (six COPD and six controls) were analyzed by targeted HM350 metabolomics, and multivariate and pathway analysis were performed by Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results: The counts of many metabolites such as amino acids, carbohydrates and carnitines were changed in both COPD patients and mice compared to controls, respectively. While lipid metabolism was changed only in COPD mice. After KEGG analysis, we found these altered metabolites involved in COPD through aging, apoptosis, oxidative stress and inflammation pathways. Conclusions: The expressions of metabolites changed in both COPD patients and cigarette smoke exposed (CS-exposed) mice. And there were also some differences between COPD patients and mouse models due to the differences between species. Our study suggested the dysregulation in amino acid metabolism, energy production pathway and perhaps lipid metabolism may be significantly related to the pathogenesis of COPD.

The role of 3-dimensional preoperative planning for primary total hip arthroplasty based on artificial intelligence technology to different surgeons: A retrospective cohort study.

Preoperative planning with computed tomography (CT)-based 3-dimensiona (3D) templating has been achieved precise placement of hip components. This study investigated the role of the software (3-dimensional preoperative planning for primary total hip arthroplasty [THA] based on artificial intelligence technology, artificial intelligence hip [AIHIP]) for surgeons with different experience levels in primary THA. In this retrospective cohort study, we included patients, who had undergone THA with the help of the AIHIP, and matched to patients, who had undergone THA without the help of the AIHIP, by age and the doctor who operated on them. The subjects were divided into 4 groups, senior surgeon (Chief of Surgery) with AIHIP group, senior surgeon without AIHIP group, junior surgeon (Associate Chief of Surgery) with AIHIP group and junior surgeon without AIHIP group. The general data, imaging index, clinical outcomes and accuracy of stem size prediction and cup size prediction were retrospectively documented for all patients. There was a significant difference in discrepancy in leg length (P = .010), neck-shaft angle (P = .025) and femoral offset (P = .031) between the healthy side and the affected side, operation duration (P < .001), decrease in hemoglobin (Hb) per 24 hours (P = .046), intraoperative radiation exposure frequency (P < .050) and postoperative complications (overall P = .035) among the patients in junior surgeon group. No significant differences were found between senior surgeon groups with respect to discrepancy in leg length (P = .793), neck-shaft angle (P = .088)and femoral offset (P = .946) between the healthy side and the affected side, operation duration (P = .085), decrease in Hb per 24 hours (P = .952), intraoperative radiation exposure frequency (P = .094) and postoperative complications (overall P = .378). The stem sizes of 95% were accurately estimated to be within 1 stem size, and 97% of the cup size estimates were accurate to within 1 cup size in senior surgeon group with AIHIP. A total of 87% stem sizes were accurately estimated to be within 1 stem size, and 85% cup sizes were accurate to within 1 cup size in junior surgeon group with AIHIP. In conclusion, our study suggests that an AI-based preoperative 3D planning system for THA is a valuable adjunctive tool for junior doctor and should routinely be performed preoperatively.