ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

Objective:To explore the value of high resolution computed tomography（HRCT） combined with Magnetic Resonance Imaging（MRI） in the diagnosis of inner ear malformation. Methods:HRCT and MRI data of 82 patients with inner ear malformations were analyzed retrospectively. HRCT MPR and CPR reconstruction of the inner ear structure, facial nerve canal and oblique sagittal MRI reconstruction of the internal auditory canal were performed. The inner ear malformations were classified, the conditions of facial nerve canal and cochlear nerve were evaluated. The association between inner ear malformation and cochlear nerve dysplasia were analyzed by Chi-square test with continuity correction. Results:Among the 82 patients with inner ear malformations,there were 49 cases of bilateral symmetry, 11 cases of bilateral asymmetry and 22 cases of unilateral inner ear malformations. Respectively, the most prevalent types were IP-Ⅱ（42.96%）, dilatation of atrium aqueduct（18.31%） and malformations of atrium and semicircular canal 19.72%. Out of 50 cases of cochlear malformations,only 3 were isolated cochlear malformations, and the rest were accompanied by other malformations of varying degrees. In the 67 ears examined by MRI, 26（38.81%） had cochlear nerve deficiency（CND）, and the incidence of CND varied with different types of inner ear malformations. Out of 142 ears, 28（19.72%） had abnormalities of the facial nerve canal. Conclusion:HRCT combined with MRI can accurately distinguish the types of inner ear malformation and effectively evaluate the facial nerve canal and cochlear nerve, and further provides the important finger and Guide value for the clinician to formulate the reasonable treatment and the operation plan.
Humans ; Ear, Inner/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Female ; Male ; Tomography, X-Ray Computed/methods* ; Child ; Adolescent ; Adult ; Child, Preschool ; Cochlear Nerve/diagnostic imaging* ; Facial Nerve/abnormalities* ; Cochlea/abnormalities* ; Infant ; Young Adult

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

Objective To explore the differences in gut microbiota among different histopathologi-cal subtypes of lung cancer.Methods A total of 80 lung cancer patients admitted to the Department of Oncology and Hematology of Anqing First People's Hospital from February 2020 to February 2024 were selected as study subjects.Meanwhile,80 healthy volunteers who underwent physical examina-tions during the same period were selected as control group.According to pathological examination re-sults,the lung cancer patients were divided into three subgroups:lung squamous cell carcinoma group,lung adenocarcinoma group,and lung small-cell cancer group.The 16S ribosomal RNA(16S rRNA)sequencing technology was used to compare the differences in gut microbiota diversity and the characteristics of species relative abundance between lung cancer patients with different patho-logical grades and the control group.Results The proportion of patients with a family history of lung cancer was higher in different lung cancer subtypes than in the control group,and the difference was statistically significant(P＜0.05).The abundance-based coverage estimator(ACE)index,Simpson index,and Shannon index of patients with different lung cancer pathological subtypes were all lower than those in the control group,and the differences were statistically significant(P＜0.05).β-diver-sity analysis showed that there were significant differences in the variation of gut microbial community structure between the control group and lung cancer patients with different pathological types(P＜0.05).The results of LEfSe indicated that there were differences in gut characteristic microbiota among patients with different pathological subtypes.Specifically,Megamonas was enriched in the LUAD group,Butyrivibrio was enriched in the LSCC group,and Akkermansia was enriched in the SCLC group.Conclusion There are significant differences in the composition of gut microbiota between lung cancer patients and the normal population,and the gut microbiota of patients with different lung cancer pathological subtypes have distinct characteristics.These differences may provide new bio-markers and therapeutic strategies for the diagnosis and treatment of lung cancer.

Objective To analyze the impact of sarcopenia on the efficacy and adverse reactions of immunotherapy combined with chemotherapy in patients with advanced gastric cancer.Methods Patients with locally advanced or metastatic gastric cancer confirmed by pathology who were not eligible for radical surgery were selected as study subjects.A body composition analyzer was used to measure the appendicular muscle mass of the patients and calculate the skeletal muscle mass index(SMI).Based on the SMI,the patients were divided into sarcopenia group and non-sarcopenia group.On the basis of nutritional intervention and comprehensive exercise therapy,the patients were administered immu-notherapy combined with chemotherapy.The efficacy and adverse reactions were evaluated.The primary endpoint was progression-free survival(PFS),and the secondary endpoints were the objec-tive response rate(ORR)and treatment-related adverse reactions.Results A total of 52 gastric cancer patients were included,with 23 in the sarcopenia group and 29 in the non-sarcopenia group.The median PFS in the non-sarcopenia group was 9.8 months(95％CI,8.9 to 12.4),and was 5.4 months in the sarcopenia group(95％CI,4.9 to 8.1).The median PFS in the non-sarcopenia group was longer than that in the sarcopenia group,and the difference was statistically significant[HR(95％CI)=0.41(0.23 to 0.73),P=0.003].The results of the multivariate Cox propor-tional hazards regression model showed that comorbidities,treatment cycles,and sarcopenia were all independent prognostic factors affecting the PFS of gastric cancer patients(P＜0.05).The ORR in the non-sarcopenia group was 48.28％(14/29),and was 17.39％(4/23)in the sarcopenia group(x2=5.276,P＜0.05).Treatment-related adverse reactions with grading ≥3 in both groups were mainly hematological toxicities.In the non-sarcopenia group,the incidence of grading ≥ 3 treat-ment-related adverse reactions was 27.59％(8/29),and the incidence of grading＜3 treatment-re-lated adverse reactions(including those with no adverse reactions)was 72.41％(21/29).In the sarcopenia group,the incidence of grading ≥3 treatment-related adverse reactions was 56.52％(13/23),and the incidence of grading＜3 treatment-related adverse reactions(including those without adverse reactions)was 43.48％(10/23).The incidence of grading ≥3 treatment-related adverse reactions in the non-sarcopenia group was lower than that in the sarcopenia group(P=0.035).Conclusion For patients with locally advanced or metastatic gastric cancer complicated with sarcopenia,the median PFS of immunotherapy combined with chemotherapy is shorter,the ORR is lower,and the incidence of treatment-related adverse reactions is increased.Therefore,ear-ly intervention for sarcopenia should be implemented to improve the quality of life of patients with advanced gastric cancer.

BACKGROUND:Studies have shown that poor dynamic postural control may lead to abnormal movement patterns during exercise,which may increase the risk of lower limb joint and anterior cruciate ligament injury.The stability of the body core is the basis of good dynamic postural control. OBJECTIVE:To investigate the effects of core stability training on dynamic postural control and risk of injury in landing movements,and to compare the differences in training effects between genders. METHODS:Thirty-five college students(male=19,female=16)were recruited for 6 weeks of core stability training.The results of the Y balance test,trunk extensor endurance test,trunk flexor endurance test,lateral bridge endurance test,and landing error scoring system were analyzed before and after training. RESULTS AND CONCLUSION:The 6-week core stability training could improve trunk extensor endurance(P＜0.001),flexor endurance(P＜0.001),and lateral abdominal muscle endurance(P＜0.001).Core stability training could improve forward distance(P=0.026),backward inward distance(P＜0.001),backward outward distance(P=0.005)and comprehensive score(P＜0.001)of Y balance test for male and female college students.Landing error scoring system scores of both male and female college students significantly decreased after 6 weeks of core stability training(P＜0.001)while increasing knee(P＜0.001)and hip flexion angles(P＜0.001),decreasing knee valgus angle(P＜0.001)at the moment of touchdown,and could increase the maximum knee flexion angle(P＜0.001)and decrease the maximum knee valgus angle(P＜0.001).It is concluded that core stability training improves dynamic postural control and improves landing movement patterns,suggesting that it may help reduce the risk of anterior cruciate ligament injury.There are no sex differences in core stability training in terms of increased trunk flexor endurance,lateral bridge muscle group endurance,improved dynamic postural control,and reduced risk of anterior cruciate ligament injury.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

OBJECTIVE To compare the cost-utility of eight programmed death 1(PD-1)/programmed cell death-ligand 1(PD-L1) inhibitor combination regimens for first-line treatment of advanced non-small cell lung cancer(NSCLC) from the perspective of Chinese healthcare system. METHODS Relevant data were derived from a published network meta-analysis and randomized controlled trails, a three-state Markov model was established to analyze the cost-utility of eight immunotherapy combinations. The robustness of results were validated through sensitivity analyses and a series of scenario analyses was also conducted. RESULTS The incremental cost-utility ratio(ICUR) of the sintilizumab plus chemotherapy group and the tislelizumab plus chemotherapy group were ￥125143.88/quality adjusted life year(QALY) and ￥189609.64/QALY, respectively, which were less than the willingness-to-pay(WTP) threshold of ￥257094/QALY, and all the ICURs of other PD-1/PD-L1 inhibitor combination regimens exceeded the WTP threshold and were not economical. Scenario analyses found that even if the medical insurance reimbursement ratio reached 80%, the different combinations of pembrolizumab, nivolumab and atezolizumab were not economical. CONCLUSION Compared with other PD-1/PD-L1 inhibitor combination regimens, sintilizumab plus chemotherapy and tislelizumab plus chemotherapy have cost-utility advantages in the first-line treatment of advanced NSCLC, which can provide a certain reference for selecting a reasonable treatment plan for NSCLC patients.