Aluminum adjuvants are widely used in the field of vaccines due to their ability to induce efficient and long-lasting immune responses and good safety profile. With the development of immunology, the requirements for adjuvants have gradually increased, and traditional aluminum adjuvants can no longer meet all the needs of application. The development of novel aluminum adjuvants has become a hot research topic in order to achieve good immunity-enhancing effects and induce specific types and strengths of immune responses. This review briefly introduces the mechanism of action and safety of aluminum adjuvants, with focus on the research progress of novel aluminum adjuvants in recent years, mainly including nano-aluminum adjuvants and composite aluminum adjuvants (aluminum adjuvants compounded with immunity-stimulating molecules or delivery carriers), and a prospect of their future research direction, aiming to provide some reference for the further development and clinical application of aluminum adjuvants.

Objective To evaluate the changes of bronchial mucosa observed by fiberoptic bronchoscopy after bronchial arterial embolization(BAE)treatment.Methods A total of 176 patients,who received BAE at the First Affiliated Hospital of Guangzhou Medical University of China from May 2019 to March 2024,were enrolled in this study.The pre-BAE and post-BAE bronchial mucosa was checked by fiberoptic bronchoscopy.Results Of the 176 patients,fiberoptic bronchoscopy showed no abnormal findings in 143 and showed abnormal findings in 33.All the abnormal findings were mucosal congestion and oedema,in some cases coexisting vascular bulge was seen,but no manifestations of ischemia or necrosis of the bronchial mucosa could be found.In 22 patients,the preoperative and postoperative 7-day fiberoptic bronchoscopy revealed that both preoperative and postoperative examinations showed no obvious abnormalities of the bronchial mucosa in 13 patients,preoperative examination had abnormalities of the bronchial mucosa in 9 patients,postoperative examination showed no obvious abnormalities of the bronchial mucosa in 3 patients,and in one patient the postoperative degree of bronchial mucosal congestion and oedema was significantly improved when compared with its preoperative degree.Conclusion BAE does not cause ischemic necrosis or shedding of bronchial mucosa,and BAE can reduce the degree of bronchial mucosal congestion in some patients.

Objective To investigate the effect of Ophiopogonin D on lipopolysaccharide(LPS)-induced apoptosis of alveolar epithelial cells by regulating the interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods A549 AT Ⅱ cells cultured in vitro were randomly divided into four groups:control group,LPS group,LPS+Ophiopogonin D group,LPS+Ophiopogonin D+colivelin(JAK2/STAT3 signal activator)group,except for the control group,and cells in all other groups were established injury models while being grouped with Ophiopogonin D and colivelin for treatment.Cell counting kit-8(CCK-8)experiment and flow cytometry were applied to detect cell proliferation and apoptosis in each group;Western blotting was applied to detect the expression of IL-6/JAK2/STAT3 signaling pathway proteins of cells in each group.Results The apoptosis rates of A549 cells in control group,LPS group,LPS+Ophiopogonin D group and LPS+Ophiopogonin D+colivelin group were(2.52±0.73)％,(52.43±4.14)％,(1.67±0.52)％and(47.94±3.43)％;IL-6 protein levels were 0.14±0.03,0.49±0.05,0.17±0.04 and 0.45±0.06,and p-JAK2/JAK2 protein levels were 0.17±0.04,0.64±0.08,0.19±0.06 and 0.61±0.07;p-STAT3/STAT3 protein levels were 0.20±0.06,0.69±0.10,0.22±0.07 and 0.65±0.09;the apoptosis rates of AT Ⅱ cells were(3.01±0.69)％,(55.16±3.94)％,(2.35±0.71)％and(50.28±3.78)％;the levels of IL-6 protein were 0.11±0.03,0.87±0.13,0.19±0.04 and 0.84±0.12;the p-JAK2/JAK2 protein levels were 0.13±0.04,0.56±0.08,0.15±0.03 and 0.53±0.07;p-STAT3/STAT3 protein levels were 0.30±0.08,0.79±0.14,0.33±0.09 and 0.75±0.13.The above indexes:control group,LPS+Ophiopogonin D group compared with LPS group,LPS+Ophiopogonin D+colivelin group compared with LPS+Ophiopogonin D group,the differences were statistically significant(all P＜0.05).Conclusion Ophiopogonin D can reduce LPS induced inflammation and oxidative stress levels by inhibiting the activation of IL-6/JAK2/STAT3 signaling pathway,ultimately reducing LPS-induced apoptosis of alveolar epithelial cells.

ObjectiveTo investigate the effect of phytoestrogen biochanin A （BCA） on liver fibrosis induced by CCl₄ in female mice with bilateral oophorectomy （ovariectomized） and its mechanism. MethodsA total of 50 ovariectomized Kunming mice were selected and given intraperitoneal injection of CCl₄ to establish a model of liver fibrosis， and then according to body weight， they were randomly divided into model group， positive control group， and low-， middle-， and high-dose BCA groups， with 10 mice in each group. In addition， 10 female mice in the same litter were given resection of a small amount of adipose tissue near both ovaries to establish the sham-operation group. The mice in the positive control group were given estradiol 2 mg/kg by gavage， and those in the low-， middle-， and high-dose BCA groups were given BCA by gavage at a dose of 25， 50， and 100 mg/kg， respectively， once a day for 7 consecutive weeks； the mice in the sham-operation group and the model group were given an equal volume of 0.5% sodium carboxymethyl cellulose solution by gavage. The mice were anesthetized and sacrificed after administration to collect samples. Liver index and uterus index were measured； HE staining and Masson staining were used to observe liver histopathological changes； the biochemical analysis was used to measure the activity of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； ELISA was used to measure the levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in liver tissue， and Western blot was used to measure the relative protein expression levels of collagen Ⅰ， transforming growth factor-beta 1 （TGF-β₁）， alpha-smooth muscle actin （α-SMA）， estrogen receptor beta （ERβ）， and p-NF-κBp65/NF-κBp65 in liver tissue. The t-test was used for comparison of continuous data between two groups； a one-way analysis of various was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. ResultsCompared with the sham-operated group， the model group had a significant increase in liver index and a significant reduction in uterus index， as well as significant increases in the activities of serum AST and ALT， the levels of IL-6 and TNF-α in liver tissue， and the protein expression levels of collagen Ⅰ， TGF-β₁， α-SMA， and p-NF-κBp65/NF-κBp65 in liver tissue （all P<0.05）， with no significant change in the expression of ERβ in liver tissue （P>0.05）， and the model group showed significant fibrosis lesions in the liver， such as hepatocyte edema， steatosis， and necrosis with inflammatory cell infiltration and hyperplasia， deposition， and staggered distribution of collagen fibers. Compared with the model group， the low-， middle-， and high-dose BCA groups had significant reductions in liver index， the activities of serum AST and ALT， the levels of IL-6 and TNF-α， and the protein expression levels of collagen Ⅰ， TGF-β₁， α-SMA， and p-NF-κBp65/NF-κBp65 in liver tissue （all P<0.05）， with no significant change in uterine index （P>0.05）， as well as a significant increase in the protein expression level of ERβ in liver tissue （P<0.05） and varying degrees of improvement in liver fibrosis lesions. ConclusionBCA can effectively improve CCL₄-induced liver fibrosis in ovariectomized female mice， possibly by upregulating ERβ to inhibit the NF-κB signaling pathway and then alleviating inflammatory response.

Objective:To retrospectively analyze the viral levels and associated factors in patients with hepatitis B virus (HBV)-related primary liver cancer (PHC) in real-world settings and further explore the correlation between low viral load (LVL) and/or low-level viremia (LLV) and PHC.Methods:Five hundred twenty-four cases with HBV-related PHC with complete pathologically confirmed data from 2013 to 2020 were included. Percentages (%) were used to express their viral load, antiviral (oral) status, patient compliance, presence or absence of cirrhosis, family history of liver cancer, and others. LVL definition: After excluding detection errors by PCR method, serum HBV DNA <50-2 000 IU/ml, and those who had received antiviral drug treatment were called LLV. Antiviral treatment (AVT) rate definition: As of the confirmed diagnosis of PHC, those who had been regularly treated using oral antiviral drugs for six months or more (≥6 months).Results:General situation: The ratio of male to female enrolled patients was 15.90:1 (493/31). Patients aged >40 years accounted for 91.98% (482 cases). Hepatitis B surface antigen (HBsAg) positivity condition: The ratio of HBsAg-positive to HBsAg-negative/anti-HBc-positive (HBsAg-/anti-HBc+) PHC patients was 5.89:1 (448/76). Among the 76 HBsAg-/anti-HBc+patients, the ratio of HBsAg-/anti-HBs+/anti-HBc+ to HBsAg-/anti-HBs-/anti-HBc+ patients was 0.95:1 (37/39). Hepatitis B e antigen (HBeA) positivity condition: The ratio of HBeAg-negative to HBeAg-positive cases was 3.23:1 (400/124). HBV DNA level condition: The medical history records of 75.00% of patients (393/524) had traceable HBV DNA test reports. Out of 393 patients, 45.04% (177/393) accounted for undetectable HBV DNA, 13.49% (53/393) accounted for LVL, 41.48% (163/393) accounted for HBV DNA exceeding the upper limit of LVL, and 4.07% (16/393) accounted for LLV. Among HBsAg-positive and HBsAg-/anti-HBc+ patients, the HBV DNA positivity rates were 59.12% (214/362) and 6.45% (2/31), respectively. Antiviral treatment condition: Among the 448 HBsAg-positive PHC patients, the total AVT rate was 18.08% (81/448), of which seven patients did not have their HBV DNA results traced back. Among them, the AVT rate of 148 patients with HBV DNA lower than the lowest detection value was 41.22% (61/148); the AVT rate of 53 patients with LVL was 18.87% (10/53); and the AVT rate of 163 patients with HBV DNA≥LVL upper limit was 1.84% (3/163). Liver cirrhosis and family history condition: 348 patients (66.41%) had liver cirrhosis. 67 patients (12.79%) had a distinct family history of HBV-related liver cirrhosis and liver cancer. Alpha-fetoprotein (AFP) condition: 514 patients underwent AFP testing, with 30.93% of the patients had normal AFP levels, and 69.07% had AFP levels exceeding the upper limit of normal values (355/514). Among them, 10 μg/L400 μg/L accounted for 34.44% (177/514) and 34.63% (178/514), respectively. Tissue typing condition: 99.05% (519/524) were hepatocellular carcinoma, and well-differentiated and moderately differentiated cases accounted for only 8.59%.Conclusions:In the real world, comprehensive, timely screening, standardized, and effective antiviral treatment have not yet been achieved for patients with chronic hepatitis B, resulting in the persistence of HBsAg and/or HBV DNA positivity (especially LVL and/or LLV). Although LVL does not account for a high proportion among all HBV-related PHC populations, the vast majority of LVL populations have not received any antiviral treatment. In addition, some PHC populations with HBV DNA>2 000 IU/ml have not received standard antiviral treatment before the onset of the disease, which should be paid attention to. At the same time, HBsAg-/anti-HBc+ populations may have latent HBV infection and may even progress to PHC. Notably, PHC may still occur after HBeAg seronegative conversion.

Objective To investigate the equivalent conversion of head injury criterion(HIC)under anterior-posterior(AP)and lateral-medial(LM)craniocerebral impact for mild craniocerebral injury in rats using motor evoked potential(MEP)and β-amyloid precursor protein(β-APP)immunohistochemistry(IHC).Methods Sixty healthy adult male SD rats were randomly divided into 0 m control group,0.5 m-AP and 0.5 m-LM injury groups,and 1 m-AP and 1 m-LM injury groups(12 rats in each group).The control group did not undergo any impact injury experiment.After the impact injury experiment,the injury and control groups were subjected to excessive anesthesia to produce β-APP immunohistochemical stained slices,and the percentage of positive area and integral optical density(IOD)in the brainstem pyramidal tract area of the slices were determined.The MEP groups were divided in the same manner as the IHC groups and the MEP amplitudes of the MEP and control groups were measured after the impact injury experiment.Results With an increase in the degree of injury,the decrease in MEP amplitude,percentage of positive areas,and IOD in the injury groups significantly increased.When the degree of injury was low,the sensitivity of IHC was higher than that of MEP.When the degree of injury was the same,the HIC in the LM direction was lower than that in the AP direction.When the HIC was the same,the degree of injury in the LM direction was greater than that in the AP direction.Conclusions The joint evaluation of MEP and β-APP can provide experimental references for the study of HIC equivalent conversion in AP-LM craniocerebral impact injury.

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

Literature regarding the impacts of heavy metal exposure on erectile dysfunction (ED) is scarce. We aimed to evaluate the correlation between 10 urinary metals and ED in a large, nationally representative adult male sample. The dataset was extracted from the National Health and Nutrition Examination Survey (NHANES) during the period of 2001-2002 and 2003-2004. Weighted proportions and multivariable logistic regression analysis adjusted for confounding variables were utilized to determine the relationship between metal exposure and ED. Weighted quantile sum (WQS) regression was utilized to evaluate the impact of a mixture of urinary metals on ED. A total of 1328 participants were included in our study. In multivariable logistic regression analysis, cobalt (Co) and antimony (Sb) were positively associated with ED (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.10-1.73, P = 0.020; and OR: 1.41, 95% CI: 1.12-1.77, P = 0.018, respectively) after full adjustment. Men in tertile 4 for Co (OR: 1.49, 95% CI: 1.02-2.41, P for trend = 0.012) and Sb (OR: 1.53, 95% CI: 1.08-2.40, P for trend = 0.041) had significantly higher odds of ED than those in tertile 1. Furthermore, the WQS index was significantly linked with increased odds of ED after full adjustment (OR: 1.31, 95% CI: 1.04-1.72, P < 0.05). Our study expanded on previous literature indicating the possible role of heavy metal exposure in the etiology of ED. The evaluation of heavy metal exposure should be included in the risk assessment of ED.
Adult ; Humans ; Male ; United States ; Erectile Dysfunction/etiology* ; Nutrition Surveys ; Metals, Heavy ; Risk Assessment

Objective:To evaluate the efficacy of neonatal resuscitation simulation exercise for perinatal medical personnel.Methods:From August 2020 to July 2021, perinatal medical personnel receiving simulated training of neonatal resuscitation in our hospital were prospectively enrolled. The professional backgrounds of the trainees were collected and their performances on both knowledge skills and behavioral skills were scored. The knowledge skills included pre-resuscitation preparation, initial resuscitation, positive pressure ventilation, tracheal intubation, chest compression and umbilical vein catheterization. The behavioral skills included situational awareness, problem solving, resource utilization, communication and leadership. SPSS 26.0 was used for data analysis.Results:Among the 200 participants, 127(63.5%) were neonatal/pediatric doctors and nurses, 65(32.5%) were obstetricians and midwives, 8(4.0%) were anesthesiologists and the ratio of doctors to nurses was 1.74∶1. The score of knowledge skills was (19.52±2.92) at the beginning of the simulation exercise and (27.02±2.72) at the end. The scores on preparation before resuscitation, initial resuscitation and positive pressure ventilation were significantly improved ( P<0.05). The score of behavioral skills was (16.60±2.34) at the beginning and (20.58±1.77) at the end. The scores of resource utilization, communication and leadership were significantly improved ( P<0.05). Conclusions:The simulation exercise provides multidisciplinary teamwork training for perinatal medical personnel, may significantly improve neonatal resuscitation skills and is worth promoting.

Objective:To investigate the clinical, genetic, and pathological features of nemaline myopathy type 8 (NEM8) caused by KLHL40 gene variation. Methods:The clinical data, gene sequencing results, and musculoskeletal pathophysiology of two cases (a pair of twins) with NEM8 admitted to our hospital in July 2022 were collected. CNKI, VIP, Wanfang, Yiigle, PubMed, Embase, and Web of Science Database were searched with the English and Chinese terms "nemaline myopathy type 8", "nemaline body myopathy type 8", and " KLHL40" from January 2007 to February 2023. The clinical, genetic, and musculoskeletal characteristics of the NEM8 cases were summarized using the descriptive statistical analysis method. Results:(1) Case report: The mother (G2P2) of the twins (Ⅳ-2 and Ⅳ-3) was conceived by IVF-embryo transfer and delivered at 37 +1 gestational weeks. The two cases were dizygotic twins whose maternal grandmother had lip and palate cleft. The first baby (Ⅳ-1) of the woman exhibited absent left pinna, contracture at the end of both fingers, talipes equinovarus in both feet and died of respiratory failure two hours after birth. Fetal edema and fetal movement delay in the twins and varus right foot in one twin were found during pregnancy. Both cases developed intrapartum asphyxia with the clinical manifestations of generalized muscle weakness, respiratory failure, dysphagia, multiple joint contractures, and fractures. The families withdrew the treatment and the twins died after maintaining life with ventilators for 53 days after birth. Whole exome sequencing of the pedigree found c.1779G>T (p.W593C) homozygous variants of the KLHL40 gene in the twins and c.1779G>T (p.W593C) heterozygous variants of the KLHL40 gene in the parents, both were de novo. Musculoskeletal pathophysiology indicated that muscle fibers are thin and round with a fetal shape and absent rod. (2) Literature review: Among the 29 cases of NEM8, including two current cases and 27 cases retrieved from 15 papers, eight cases terminated the pregnancies, and 21 were live births; seven cases (24.1%) with positive family history; 19 cases (65.5%) were found with abnormalities during pregnancy, including abnormal fetal movements, polyhydramnios, joint contracture, and fetal edema. Of the 21 live births, 20 cases had intrapartum asphyxia, 21 had postnatal respiratory failure, 20 had generalized muscle weakness, and 19 had dysphagia. Among the 29 cases, 17 cases (58.6%) were homozygous variants of the KLHL40 gene, and 12 cases (41.4%) were compound heterozygous variants. The detection rate of c.1516A>C(p.Thr506Pro) was the highest [72.4% (21/29)], followed by c.602G>A(p.Trp201*) [17.2% (5/29)]. Out of the 15 cases who underwent musculoskeletal pathological examination, all had abnormal muscle fiber size and morphology; 10 cases had rods. Conclusions:NEM8 should be considered for those with abnormal fetal movements, polyhydramnios, joint malformation, fetal edema during the fetal period and failure to establish respiration at birth as well as postnatal generalized muscle weakness, respiratory failure, dysphagia, multiple joint contractures, and fracture. Moreover, genetic detection should be performed as soon as possible. NEM8 can be diagnosed in ones with KLHL40 gene homozygous or compound heterozygous variants and musculoskeletal pathological results of abnormal size and shape of muscle fibers, regardless of the presence of rods.