Therapeutic drug monitoring of linezolid in Chinese premature neonates: a population pharmacokinetic analysis and dosage optimization.

This study aimed to develop a pharmacokinetic model of linezolid in premature neonates and evaluate and optimize the administration regimen. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect the blood concentration data of 54 premature neonates after intravenous administration of linezolid, and the relevant clinical data were collected. The population pharmacokinetic (PPK) model was established by nonlinear mixed effects modeling. Based on the final model parameters, the optimal administration regimen of linezolid in premature neonates with different body surface areas (BSA) was simulated and evaluated. The pharmacokinetic properties of linezolid in premature neonates are best described by a single-compartment model with primary elimination. The population typical values for apparent volume of distribution and clearance were 0.783 L and 0.154 L/h, respectively. BSA was a statistically significant covariate with clearance (CL) and volume of distribution (Vd). Monte Carlo simulations showed that the optimal administration regimen for linezolid in premature neonates was 6 mg/kg q8h for BSA 0.11 m2, 7 mg/kg q8h for BSA 0.13 m2, and 9 mg/kg q8h for BSA 0.15 m2 with minimum inhibitory concentration (MIC) ≤1 mg/L, 7 mg/kg q8h for BSA 0.11 m2, 8 mg/kg q8h for BSA 0.13 m2, and 10 mg/kg q8h for BSA 0.15 m2 with MIC = 2 mg/L. A pharmacokinetic model was developed to predict the blood concentration on linezolid in premature neonates. Based on this model, the optimal administration regimen of linezolid in premature neonates needs to be individualized according to different BSA levels.

Recent Progress of CircRNAs in Hematological Malignancies.

Circular RNAs (circRNAs) are now recognized as key regulators in the epigenetic control of genetic expression, being involved in a wide range of cellular activities such as proliferation, differentiation, and apoptosis. Their unique closed-loop structure endows them with stability and resistance to exonuclease degradation, making them not only key regulatory molecules within the cell but also promising biomarkers for disease diagnosis and prognosis, particularly in hematological malignancies. This review comprehensively explores the role of circRNAs in the pathogenesis, progression, and therapeutic resistance of common hematological malignancies. Furthermore, the review delves into the prognostic significance of circRNAs, underscoring their potential in predicting disease outcomes and treatment response. Given their extensive involvement in cancer biology, circRNAs present a frontier for novel therapeutic strategies.

High levels of mitochondrial dynamics, autophagy, and apoptosis contribute to stable testicular status in hibernating Daurian ground squirrels.

Daurian ground squirrels (Spermophilus dauricus) experience various stress states during winter hibernation, but the impact on testicular function remains unclear. This study focused on the effects of changes in testicular autophagy, apoptosis, and mitochondrial homeostasis signaling pathways at various stages on the testes of Daurian ground squirrels. Results indicated that: (1) During winter hibernation, there was a significant increase in seminiferous tubule diameter and seminiferous epithelium thickness compared to summer. Spermatogonia number and testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were higher during inter-bout arousal, suggesting that the testes remained stable during hibernation. (2) An increased number of mitochondria with intact morphology were observed during hibernation, indicating that mitochondrial homeostasis may contribute to testicular stability. (3) DNA fragmentation was evident in the testes during the hibernation and inter-bout arousal stages, with the highest level of caspase3 enzyme activity detected during inter-bout arousal, together with elevated levels of Bax/Bcl-2 and Lc3 II/Lc3 I, indicating an up-regulation of apoptosis and autophagy signaling pathways during hibernation. (4) The abundance of DRP1, MFF, OPA1, and MFN2 proteins was increased, suggesting an up-regulation of mitochondrial dynamics-related pathways. Overall, testicular autophagy, apoptosis, and mitochondrial homeostasis-related signaling pathways were notably active in the extreme winter environment. The well-maintained mitochondrial morphology may favor the production of reproductive hormones and support stable testicular morphology.

Apoptosis, Mitochondrial Autophagy, Fission, and Fusion Maintain Mitochondrial Homeostasis in Mouse Liver Under Tail Suspension Conditions.

Microgravity can induce alterations in liver morphology, structure, and function, with mitochondria playing an important role in these changes. Tail suspension (TS) is a well-established model for simulating the effects of microgravity on muscles and bones, but its impact on liver function remains unclear. In the current study, we explored the regulatory mechanisms of apoptosis, autophagy, fission, and fusion in maintaining liver mitochondrial homeostasis in mice subjected to TS for 2 or 4 weeks (TS2 and TS4). The results showed the following: (1) No significant differences were observed in nuclear ultrastructure or DNA fragmentation between the control and TS-treated groups. (2) No significant differences were detected in the mitochondrial area ratio among the three groups. (3) Cysteine aspartic acid-specific protease 3 (Caspase3) activity and the Bcl-2-associated X protein (bax)/B-cell lymphoma-2 (bcl2) ratio were not higher in the TS2 and TS4 groups compared to the control group. (4) dynamin-related protein 1 (DRP1) protein expression was increased, while mitochondrial fission factor (MFF) protein levels were decreased in the TS2 and TS4 groups compared to the control, suggesting stable mitochondrial fission. (5) No significant differences were observed in the optic atrophy 1 (OPA1), mitofusin 1 and 2 (MFN1 and MFN2) protein expression levels across the three groups. (6) Mitochondrial autophagy vesicles were present in the TS2 and TS4 groups, with a significant increase in Parkin phosphorylation corresponding to the duration of the TS treatment. (7) ATP synthase and citrate synthase activities were significantly elevated in the TS2 group compared to the control group but were significantly reduced in the TS4 group compared to the TS2 group. In summary, the coordinated regulation of apoptosis, mitochondrial fission and fusion, and particularly mitochondrial autophagy preserved mitochondrial morphology and contributed to the restoration of the activities of these two key mitochondrial enzymes, thereby maintaining liver mitochondrial homeostasis in mice under TS conditions.

Loss and recovery of myocardial mitochondria in mice under different tail suspension time: Apoptosis and mitochondrial fission, fusion and autophagy.

Long-term weightlessness in animals can cause changes in myocardial structure and function, in which mitochondria play an important role. Here, a tail suspension (TS) Kunming mouse (Mus musculus) model was used to simulate the effects of weightlessness on the heart. We investigated the effects of 2 and 4 weeks of TS (TS2 and TS4) on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling. Our study revealed significant changes in the ultrastructural features of cardiomyocytes in response to TS. The results showed: (1) mitochondrial swelling and disruption of cristae in TS2, but mitochondrial recovery and denser cristae in TS4; (2) an increase in the total number of mitochondria and number of sub-mitochondria in TS4; (3) no significant changes in the nuclear ultrastructure or DNA fragmentation among the two TS groups and the control group; (4) an increase in the bax/bcl-2 protein levels in the two TS groups, indicating increased activation of the bax-mediated apoptosis pathway; (5) no change in the phosphorylation ratio of dynamin-related protein 1 in the two TS groups; (6) an increase in the protein levels of optic atrophy 1 and mitofusin 2 in the two TS groups; and (7) in comparison to the TS2 group, an increase in the phosphorylation ratio of parkin and the ratio of LC3II to LC3I in TS4, suggesting an increase in autophagy. Taken together, these findings suggest that mitochondrial autophagy and fusion levels increased after 4 weeks of TS, leading to a restoration of the bax-mediated myocardial apoptosis pathway observed after 2 weeks of TS. NEW FINDINGS: What is the central question of this study? What are the effects of 2 and 4 weeks of tail suspension on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling? What is the main finding and its importance? Increased mitochondrial autophagy and fusion levels after 4 weeks of tail suspension help to reshape the morphology and increase the number of myocardial mitochondria.

[Association of maternal isolated thyroid peroxidase antibody positive in the first trimester with fetal growth].

OBJECTIVE: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. METHODS: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. RESULTS: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (ß=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (ß=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (ß=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (ß=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. CONCLUSION: The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.

Effects of short daylight and mild low temperature on mitochondrial degeneration in the testis of Cricetulus barabensis.

In this study, we investigated the mitochondrial energy supply capacity and molecular mechanisms of apoptosis, mitochondrial fission, and mitophagy in regulating mitochondrial degeneration in testis of striped dwarf hamsters (Cricetulus barabensis) under mild low temperature (15°C) and short daylight (10 h:14 h) conditions. Results showed that under moderate daylight and mild low temperature (ML), short daylight and moderate temperature (SM), short daylight and mild low temperature (SL) conditions, the mitochondria were swollen and cristae were disrupted. Compared with the moderate daylight & moderate temperature group (MM; 12 h:12 h, 22°C), the number of mitochondria was significantly decreased in the SM and SL groups. Both short daylight and mild low temperature reduced the protein expression of citrate synthase, thus the energy supply capacity of mitochondria may be weakened. Compared with the MM group, bax/bcl2 protein expression was higher in three treatment groups, and caspase3 activity increased in SM and SL groups, suggesting that short daylight can induce apoptosis. DRP1 protein expression showed no difference in four groups, while the FIS1 protein expression was significantly decreased in three treatment groups, this indicates that short daylight and mild low temperature can increase mitochondrial fission level. PINK1 protein expression was significantly increased in ML and SL groups, indicates that mild low temperature will lead to increased mitophagy level. Generally, short daylight induced degeneration of mitochondria in the testis of hamsters mainly by increasing apoptosis, while under mild low temperature, balanced regulation of mitophagy and mitochondrial fission appear to contribute to the protection of mitochondria.

Hippocampal µ-opioid receptors on GABAergic neurons mediate stress-induced impairment of memory retrieval.

Stressful life events induce abnormalities in emotional and cognitive behaviour. The endogenous opioid system plays an essential role in stress adaptation and coping strategies. In particular, the µ-opioid receptor (µR), one of the major opioid receptors, strongly influences memory processing in that alterations in µR signalling are associated with various neuropsychiatric disorders. However, it remains unclear whether µR signalling contributes to memory impairments induced by acute stress. Here, we utilized pharmacological methods and cell-type-selective/non-cell-type-selective µR depletion approaches combined with behavioural tests, biochemical analyses, and in vitro electrophysiological recordings to investigate the role of hippocampal µR signalling in memory-retrieval impairment induced by acute elevated platform (EP) stress in mice. Biochemical and molecular analyses revealed that hippocampal µRs were significantly activated during acute stress. Blockage of hippocampal µRs, non-selective deletion of µRs or selective deletion of µRs on GABAergic neurons (µRGABA) reversed EP-stress-induced impairment of memory retrieval, with no effect on the elevation of serum corticosterone after stress. Electrophysiological results demonstrated that stress depressed hippocampal GABAergic synaptic transmission to CA1 pyramidal neurons, thereby leading to excitation/inhibition (E/I) imbalance in a µRGABA-dependent manner. Pharmaceutically enhancing hippocampal GABAA receptor-mediated inhibitory currents in stressed mice restored their memory retrieval, whereas inhibiting those currents in the unstressed mice mimicked the stress-induced impairment of memory retrieval. Our findings reveal a novel pathway in which endogenous opioids recruited by acute stress predominantly activate µRGABA to depress GABAergic inhibitory effects on CA1 pyramidal neurons, which subsequently alters the E/I balance in the hippocampus and results in impairment of memory retrieval.

Estrogen receptor 2 mediates intraspecific aggressive behaviors of the female Cricetulus barabensis in the estrous cycle.

The social behavior mechanisms have not been thoroughly reported in the solitary female striped dwarf hamster (Cricetulus barabensis). In this study, the handling bag test and neutral arena measurements were used to detect the changes of aggression in the face of rivals of different genders of wild striped dwarf hamsters. We found that female hamsters had the highest aggressive performance in proestrus, followed by estrus, and the lowest in metestrus and the dioestrus, and the increased aggression during the proestrus or estrus period was low-intensity aggression such as intimidation, shock, boxing and counterattack, or even ritualized non-harmful behaviors to drive away opponents. When confronted with male individuals, aggression in females decreased significantly during estrus. The concentration of plasma estradiol was the highest in estrus and the lowest in metestrus and dioestrus. In contrast, estrogen receptor 2 relative expression in the hypothalamus is the lowest in proestrus and highest in metestrus and dioestrus. Besides, both estradiol levels in plasma and estrogen receptor 2 mRNA in the hypothalamus were associated with aggression. These results will broaden our understanding of the molecular mechanism of how breeding phenotype is an essential driver in changing the social behavior of female Cricetulus barabensis.

c-Myc controls the fate of neural progenitor cells during cerebral cortex development.

The anatomical structure of the mammalian cerebral cortex is the essential foundation for its complex neural activity. This structure is developed by proliferation, differentiation, and migration of neural progenitor cells (NPCs), the fate of which is spatially and temporally regulated by the proper gene. This study was used in utero electroporation and found that the well-known oncogene c-Myc mainly promoted NPCs' proliferation and their transformation into intermediate precursor cells. Furthermore, the obtained results also showed that c-Myc blocked the differentiation of NPCs to postmitotic neurons, and the expression of telomere reverse transcriptase was controlled by c-Myc in the neocortex. These findings indicated c-Myc as a key regulator of the fate of NPCs during the development of the cerebral cortex.

Novel ultrastructural findings on cardiac mitochondria of huddling Brandt's voles in mild cold environment.

Reduced ambient temperature has a damaging effect on mammalian myocardium. Huddling as a cooperative behavior has evolved in social mammals as a strategy to maximize adaptation to environmental cooling. Here, we studied the effects of huddling behavior on mitochondrial morphology, number, and function in the myocardia of Brandt's voles (Lasiopodomys brandtii) under cool environmental temperatures (15 °C). Results showed (1) mitochondrial swelling and cristae disruption in the cool huddling group (CH) and cool separated group (CS). Compared to the control group (CON, 22 °C), damaged mitochondria in the cool huddling and separated groups reached >90%; however, total number of mitochondria in the CH group was similar to that in the CON group. (2) ATP synthase activity was lowest in the CS group, whereas citrate synthetase activity was maintained among the three treatment groups. (3) Bax/bcl2 protein expression in the CH and CS groups was higher than that in the CON group, whereas DNA fragmentation, nuclear number, and caspase3 activity showed no significant differences among the three groups. (4) The protein expression levels of dynamin-related protein1 and mitochondrial fission factor were highest in the CH group. (5) Both protein expression of PINK1 and phosphorylation ratio of Parkin showed the pattern CS > CH > CON. (6) Total number of mitochondria was higher in males than in females. In general, the increased mitochondrial fission level observed in huddling voles partially counteracted the decrease in myocardial mitochondria caused by the increase in autophagy.

Calcium/calmodulin-dependent protein kinase II regulates mammalian axon growth by affecting F-actin length in growth cone.

While axon regeneration is a key determinant of functional recovery of the nervous system after injury, it is often poor in the mature nervous system. Influx of extracellular calcium (Ca2+ ) is one of the first phenomena that occur following axonal injury, and calcium/calmodulin-dependent protein kinase II (CaMKII), a target substrate for calcium ions, regulates the status of cytoskeletal proteins such as F-actin. Herein, we found that peripheral axotomy activates CaMKII in dorsal root ganglion (DRG) sensory neurons, and inhibition of CaMKII impairs axon outgrowth in both the peripheral and central nervous systems (PNS and CNS, respectively). Most importantly, we also found that the activation of CaMKII promotes PNS and CNS axon growth, and regulatory effects of CaMKII on axon growth occur via affecting the length of the F-actin. Thus, we believe our findings provide clear evidence that CaMKII is a critical modulator of mammalian axon regeneration.

Regulation of adult mammalian intrinsic axonal regeneration by NF-κB/STAT3 signaling cascade.

The inflammatory response is a critical regulator for the regeneration of axon following nervous system injury. Nuclear factor-kappa B (NF-κB) is characteristically known for its ubiquitous role in the inflammatory response. However, its functional role in adult mammalian axon growth remains elusive. Here, we found that the NF-κB signaling pathway is activated in adult sensory neurons through peripheral axotomy. Furthermore, inhibition of NF-κB in peripheral sensory neurons attenuated their axon growth in vitro and in vivo. Our results also showed that NF-κB modulated axon growth by repressing the phosphorylation of STAT3. Furthermore, activation of STAT3 significantly promoted adult optic nerve regeneration. Taken together, the findings of our study indicated that NF-κB/STAT3 cascade is a critical regulator of intrinsic axon growth capability in the adult nervous system.

Visible-Light-Driven Alkyne Hydro-/Carbocarboxylation Using CO2 via Iridium/Cobalt Dual Catalysis for Divergent Heterocycle Synthesis.

We present herein the first visible-light-driven hydrocarboxylation as well as carbocarboxylation of alkynes using CO2 via an iridium/cobalt dual catalysis. Such transformations provide access to various pharmaceutically important heterocycles in a one-pot procedure from readily available alkynes. Coumarins, 2-quinolones, and 2-benzoxepinones were directly accessed through a one-pot alkyne hydrocarboxylation/alkene isomerization/cyclization sequence in which the Ir photocatalyst serves a dual role to promote single-electron transfer in alkyne hydrocarboxylation and energy transfer in the subsequent alkene isomerization. Moreover, an unprecedented cobalt carboxylation/acyl migration cascade enables alkyne difunctionalization to introduce γ-hydroxybutenolides with high efficiency. We expect that this cascade strategy will inspire new perspectives for alkyne and alkene difunctionalization.

Visible-Light-Mediated Metal-Free Difunctionalization of Alkenes with CO2 and Silanes or C(sp3 )-H Alkanes.

Catalytic alkene difunctionalization via Si-H and C-H activations represents an ideal atom- and step-economic pathway for quick assembly of molecular complexity. We herein developed a visible-light-promoted metal-free difunctionalization of alkenes using abundant CO2 and readily available Si-H and C(sp3 )-H bonds as feedstocks. Through the merger of photoredox and hydrogen-atom-transfer catalysis, a variety of value-added compounds, such as ß-silacarboxylic acids and acids bearing a γ-heteroatom (e.g., N, O, S) could be directly accessed from simple alkenes in a redox-neutral fashion.

[Effect of opioid receptors on acute stress-induced changes in recognition memory].

Although ample evidence has shown that acute stress impairs memory, the influences of acute stress on different phases of memory, such as acquisition, consolidation and retrieval, are different. Experimental data from both human and animals support that endogenous opioid system plays a role in stress, as endogenous opioid release is increased and opioid receptors are activated during stress experience. On the other hand, endogenous opioid system mediates learning and memory. The aim of the present study was to investigate the effect of acute forced swimming stress on recognition memory of C57 mice and the role of opioid receptors in this process by using a three-day pattern of new object recognition task. The results showed that 15-min acute forced swimming damaged the retrieval of recognition memory, but had no effect on acquisition and consolidation of recognition memory. No significant change of object recognition memory was found in mice that were given naloxone, an opioid receptor antagonist, by intraperitoneal injection. But intraperitoneal injection of naloxone before forced swimming stress could inhibit the impairment of recognition memory retrieval caused by forced swimming stress. The results of real-time PCR showed that acute forced swimming decreased the µ opioid receptor mRNA levels in whole brain and hippocampus, while the injection of naloxone before stress could reverse this change. These results suggest that acute stress may impair recognition memory retrieval via opioid receptors.

Construction of Tropane Derivatives by the Organocatalytic Asymmetric Dearomatization of Isoquinolines.

A chiral-NHC-catalyzed highly diastereo- and enantioselective dearomatizing double Mannich reaction of isoquinolines was developed that provides a powerful and straightforward synthetic route toward substituted tropane derivatives with four contiguous stereocenters. A unique feature of this strategy is the use of readily available isoquinolines to provide two reactive sites for dearomatization, thus opening up an unprecedented approach to tropane derivatives with excellent stereoselectivity. The four-component reactions proceeded smoothly with good results. Thus, the present method is suitable for the diversity-oriented synthesis of useful tropane derivatives with high efficiency.

Pathogen detection by targeted next-generation sequencing test in adult hematological malignancies patients with suspected infections.

Background: Infections in patients with hematological malignancies (HM) are a significant cause of morbidity and mortality. Timely and effective empirical anti-infective treatment can reduce the infection-related mortality rate. Targeted next-generation sequencing (tNGS) offers a rapid diagnostic approach for identifying diverse pathogens in these patients. However, relevant research is still limited to adult patients with HM. Methods: We conducted a retrospective analysis of adult HM patients admitted to our hospital from March 2023 to September 2023, focusing on their clinical characteristics and the results of both tNGS and conventional microbiological tests (CMTs). We evaluated the performance of tNGS and CMTs in pathogenic diagnosis and described the distribution characteristics of pathogens in adult HM patients with infections. Results: The study included 209 samples collected from 137 patients. Results showed that the overall pathogen detection rate differed significantly between tNGS and CMTs (60.3% vs. 24.4%, p < 0.001). The sensitivity (69.7% vs. 35.9%), negative predictive value (NPV) (48.2% vs. 42.4%), and accuracy (66.5% vs. 56.5%) of pathogen detection were notably superior with tNGS compared to CMTs. Among the 142 samples with clinically diagnosed infections, tNGS combined with CMTs identified a definite or probable microbial etiology in 114 samples (80.3%). Of the 36 samples with concordant positive results from both tNGS and CMTs, 72.2% (26/36) exhibited full or partial agreement. Our study further showed the highest detection rate for viral infections (57.0%), predominantly for Epstein-Barr virus (DNA-V, 18.3%). Followed by bacterial infections (46.5%), the detection rate of Gram-negative bacteria (G+, 35.9%) was higher than that of Gram-positive bacteria (G-, 21.8%) in this study. Klebsiella pneumoniae (G-, 12.7%) had the highest detection rate among these emerging bacteria, followed by Pseudomonas aeruginosa (G-, 10.6%) and Enterococcus faecium (G+, 7.7%). Bacterial-viral coinfections were the most common type of mixed infection (35.5%). Conclusion: In conclusion, tNGS outperforms CMTs in both sensitivity and pathogen spectrum. Therefore, it can serve as an adjunct to CMTs to facilitate the precise adjustment of anti-infective regimens for adult HM patients. Our findings establish a basis for formulating empirical anti-infective therapy strategies tailored to the pathogen distribution in this patient population.

Assessing recent recurrence after hepatectomy for hepatitis B-related hepatocellular carcinoma by a predictive model based on sarcopenia.

BACKGROUND: Sarcopenia may be associated with hepatocellular carcinoma (HCC) following hepatectomy. But traditional single clinical variables are still insufficient to predict recurrence. We still lack effective prediction models for recent recurrence (time to recurrence < 2 years) after hepatectomy for HCC. AIM: To establish an interventable prediction model to estimate recurrence-free survival (RFS) after hepatectomy for HCC based on sarcopenia. METHODS: We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time, and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography. 94 of these patients were enrolled for external validation. Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort. A nomogram model was developed to predict the RFS of HCC patients, and its predictive performance was validated. The predictive efficacy of this model was evaluated using the receiver operating characteristic curve. RESULTS: Multivariate analysis showed that sarcopenia [Hazard ratio(HR) = 1.767, 95%CI: 1.166-2.678, P < 0.05], alpha-fetoprotein ≥ 40 ng/mL (HR = 1.984, 95%CI: 1.307-3.011, P < 0.05), the maximum diameter of tumor > 5 cm (HR = 2.222, 95%CI: 1.285-3.842, P < 0.05), and hepatitis B virus DNA level ≥ 2000 IU/mL (HR = 2.1, 95%CI: 1.407-3.135, P < 0.05) were independent risk factors associated with postoperative recurrence of HCC. Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease (SAMD) was established combined with other the above risk factors. The area under the curve of the SAMD model was 0.782 (95%CI: 0.705-0.858) in the training cohort (sensitivity 81%, specificity 63%) and 0.773 (95%CI: 0.707-0.838) in the validation cohort. Besides, a SAMD score ≥ 110 was better to distinguish the high-risk group of postoperative recurrence of HCC. CONCLUSION: Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC. A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC, which is superior to other models and contributes to prognosis prediction.

Primary pancreatic peripheral T-cell lymphoma: A case report.

BACKGROUND: Primary pancreatic lymphoma (PPL) is an exceedingly rare tumor with limited mention in scientific literature. The clinical manifestations of PPL are often nonspecific, making it challenging to distinguish this disease from other pancreatic-related diseases. Chemotherapy remains the primary treatment for these individuals. CASE SUMMARY: In this case study, we present the clinical details of a 62-year-old woman who initially presented with vomiting, abdominal pain, and dorsal pain. On further evaluation through positron emission tomography-computed tomography, the patient was considered to have a pancreatic head mass. However, subsequent endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) revealed that the patient had pancreatic peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin, decitabine, and oxaliplatin (brentuximab vedotin and Gemox). The patient had significant improvement in radiological findings at the end of the first cycle. CONCLUSION: Primary pancreatic PTCL-NOS is a malignant and heterogeneous lymphoma, in which the clinical manifestations are often nonspecific. It is difficult to diagnose, and the prognosis is poor. Imaging can only be used for auxiliary diagnosis of other diseases. With the help of immunostaining, EUS-FNA could be used to aid in the diagnosis of PPL. After a clear diagnosis, chemotherapy is still the first-line treatment for such patients, and surgical resection is not recommended. A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma. However, identifying new CD30-targeted therapies for different types of lymphoma is urgently needed. In the future, further research on antitumor therapy should be carried out to improve the survival prognosis of such patients.