[A study on the hearing protection and intervention effects of silicone earplug usage among manufacturing workers].

Objective: To assess the efficacy of silicone earplugs in protecting workers exposed to noise in a typical manufacturing environment, and to provide training interventions for workers who do not achieve the anticipated noise reduction levels, as well as examining the spectral characteristics of earplug attenuation. Methods: From June to August 2022, a total of 294 noise-exposed workers in two manufacturing enterprises equipped with the same type of earplug were studied by cluster sampling method, by conducting questionnaire surveys, collecting data, fitting tests, and providing trainings, the current noise exposure levels of workers in the industry as well as the perception about the earplug were understood. Additionally, the attenuation before and after intervention in workplace were measured, the spectral characteristics of noise reduction were were described and compared. Results: The percentage of workers with Personal Attenuation Rating (PAR) of 0 is 32.7% (96/294), and the baseline pass rates are all below 60%. There were no significant differences in pass rates based on gender, age, noise exposure, education level, or cognition of earplug effectiveness. After adjusting the way that earplugs are worn or changing the type of earplugs, all workers were able to meet their noise reduction requirements. The median PAR improvement for both companies is above 10 dB. The noise attenuation of the earplug vary with frequency, with lower attenuation at 4 000 Hz and higher attenuation at 8 000 Hz, showing some deviation from the nominal values. Conclusion: The difference between the actual sound attenuation value of earplugs and the nominal value is related to the noise frequency. When using silicone earplugs, attention should be paid to the spectral composition of the noise in the workplace.

[Analysis on the characteristics of natural foci of hemorrhagic fever with renal syndrome in Gansu Province, 2012-2022].

Objective: To explore the characteristics of natural foci of hemorrhagic fever with renal syndrome (HFRS) in Gansu Province. Methods: The information of HFRS case data and rodent density monitoring data from 2012 to 2022 in Gansu Province were collected and epidemiological methods were used to analyze and investigate the characteristics of the epidemic focus. Results: A total of 869 cases of HFRS were reported, and four patients died from 2012 to 2022. The annual incidence rate is between 0.05 per 100 000 and 1.21 per 100 000. The cases were mainly distributed in the eastern, southeast, southern, and south of the central region of Gansu Province. Most cases were distributed between age 20-60, and the sex ratio was 1.85∶1 (564∶305). Most cases were farmers (61.80%, 537/869), herdsmen (19.79%,172/869) and students (6.33%, 55/869). In a wild rat-type epidemic focus,the incidence peak was from November to January of the following year. The natural rodent hosts of HFRS were Rattus norvegicus, Apodemus agrarius, and Mus musculus. The hantaan virus carriage rates were 2.79% (21/754), 0.42% (5/1 179) and 0.31% (2/643),respectively. Three epidemic foci were defined: two derived from the Pingliang and Gannan prefecture new outbreaks epidemic foci, respectively, while the other was the residue of the Dingxi epidemic focus. Conclusions: The southern, south of the central region and eastern part of Gansu Province are current key HFRS epidemic foci dominated by Rattus norvegicus, Apodemus agrarius, and Mus musculus, respectively. The virus genotype is hantaan virus. Case reporting areas should strengthen epidemic monitoring; the key epidemic areas should strengthen and implement various prevention and control measures to reduce the harm caused by HFRS.

[Research and discovery of "inner GPS" of brain].

Since the 20th century, with the progress of brain science research, scientists have discovered the brain GPS, revealing the mechanism of brain spatial cognition. The discovery process of brain GPS has gone through three stages. In 1971, John O'Keefe discovered the position cells in the hippocampus of the brain, which was the beginning of the research on the GPS in the brain; In 1900, James Rank discovered the head direction cells in the medial entorhinal cortex of the brain, and the research on the GPS in the brain made a breakthrough; In 2005, Edvard I. Moser and his wife discovered grid cells, marking the maturity of the research on GPS in the brain. The discovery of intracerebral GPS not only reveals the spatial cognitive function of the brain at the cellular level, but also provides a theoretical basis for the study of diseases related to the nervous system.

A patient with spinal cavernous vascular malformation: case report and review of the literature.

BACKGROUND: Spinal cavernous vascular malformation (SCM) is a rare type of spinal vascular malformation that can be easily misdiagnosed and overlooked, accounting for 5%-12% of all spinal vascular malformations. To date, surgical resection has been the gold standard for treating SCM, particularly in symptomatic patients. The risk of secondary hemorrhage in SCM is as high as 66%. Therefore, early, timely, and accurate diagnosis is crucial for patients with SCM. CASE REPORT: In this report, we describe a 50-year-old female patient who was admitted to the hospital with recurrent bilateral lower extremity pain and numbness for 10 years, with recurring symptoms for 4 months. The patient's symptoms initially improved after conservative treatment but then worsened again. An MRI revealed a spinal cord hemorrhage, and after surgical treatment, the patient's symptoms improved significantly. A postoperative pathological examination confirmed the diagnosis of SCM. CONCLUSIONS: This case, along with a review of the literature, suggests that for SCM, early surgery using techniques such as microsurgery and intraoperative evoked potential monitoring may result in better outcomes for the patient.

[Study of the urban-impact on microbial communities and their virulence factors and antibiotic resistance genomes in the Nandu River, Haikou].

Objective: To explore the changes in bacterial community structure, antibiotic resistance genome, and pathogen virulence genome in river water before and after the river flowing through Haikou City and their transmission and dispersal patterns and to reveal anthropogenic disturbance's effects on microorganisms and resistance genes in the aquatic environment. Methods: The Nandu River was divided into three study areas: the front, middle and rear sections from the upstream before it flowed through Haikou City to the estuary. Three sampling sites were selected in each area, and six copies of the sample were collected in parallel at each site and mixed for 3 L per sample. Microbial community structure, antibiotic resistance, virulence factors, and mobile genetic elements were analyzed through bioinformatic data obtained by metagenomic sequencing and full-length sequencing of 16S rRNA genes. Variations in the distribution of bacterial communities between samples and correlation of transmission patterns were analyzed by principal co-ordinates analysis, procrustes analysis, and Mantel test. Results: As the river flowed through Haikou City, microbes' alpha diversity gradually decreased. Among them, Proteobacteria dominates in the bacterial community in the front, middle, and rear sections, and the relative abundance of Proteobacteria in the middle and rear sections was higher than that in the front segment. The diversity and abundance of antibiotic resistance genes, virulence factors, and mobile genetic elements were all at low levels in the front section and all increased significantly after flow through Haikou City. At the same time, horizontal transmission mediated by mobile genetic elements played a more significant role in the spread of antibiotic-resistance genes and virulence factors. Conclusions: Urbanization significantly impacts river bacteria and the resistance genes, virulence factors, and mobile genetic elements they carry. The Nandu River in Haikou flows through the city, receiving antibiotic-resistant and pathogen-associated bacteria excreted by the population. In contrast, antibiotic-resistant genes and virulence factors are enriched in bacteria, which indicates a threat to environmental health and public health. Comparison of river microbiomes and antibiotic resistance genomes before and after flow through cities is a valuable early warning indicator for monitoring the spread of antibiotic resistance.

[Drug resistance and genomic characteristics of a strain of O139 Vibrio cholerae isolated from human bloodstream infection].

Objective: To analyze the drug resistance and genomic characteristics of a strain of serogroup O139 Vibrio cholerae producing cholera toxin isolated from the bloodstream of a person with bacteremia. Methods: The broth dilution method and automatic drug sensitivity analyzer were used to determine the antibiotic sensitivity of the strain. The complete genome sequence of the strain was obtained by using second-generation gene sequencing and nanopore sequencing. BLAST software was used for comparison and analysis with CARD, Resfinder, ISfinder, VFDB, and other databases. The drug-resistant genes, insertion sequences and virulence genes carried by the strain were identified. MEGA 5.1 software was used to construct a genetic phylogenetic tree based on the core genomic single nucleotide polymorphisms. Results: V. cholerae SH400, as the toxigenic strain, carried multiple virulence-related genes and four virulence islands. The strain was resistant to streptomycin, tetracycline and cotrimoxazole, carrying corresponding drug-resistant genes. The strain also carried IncA/C plasmid with the size of 172914 bp and contained 10 drug-resistant genes. Combined with the genomic evolutionary relationship, this study found that the drug-resistant genes and drug-resistant plasmids carried among strains showed certain aggregation. The traditional ST type of strain SH400 was ST69, and the cgMLST type was a new type highly similar to cgST-252. Conclusion: This strain of serogroup O139 V. cholerae carries the ctxAB gene, multiple drug-resistant genes and IncA/C plasmid, and there are multiple drug-resistant islands.

[Application of bridging study design in preventive vaccine clinical trials].

Bridging study in vaccine clinical trials means a series of small-scale additional tests on the basis that the original safety and effectiveness of a vaccine have been confirmed in clinical trials, to prove that the characteristics of safety, immunogenicity and effectiveness of a vaccine are similar or consistent after component, population and immunization procedure change to other types which can extrapolate data from existing clinical trials. Compared with traditional vaccine clinical trials, bridging trials can promote the approval of vaccines to the market, accelerate the expansion of vaccine application, and promote the use of vaccines across regions and populations. In recent years, the application of bridge study design in vaccine clinical research has become more and more common. In order to better guide and promote the application of bridging trial design in the field of vaccine clinical research, we reviewed the design characteristics and application examples of bridging study design in vaccine clinical trials, and systematically elaborated the design ideas, key points and statistical evaluation methods of bridging study.

Efficacy and safety of intracoronary pro-urokinase injection during percutaneous coronary intervention in treating ST elevation myocardial infarction patients: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Intracoronary injection of pro-urokinase (Pro-UK) during percutaneous coronary intervention (PCI) seems to be a promising treatment in improving myocardial perfusion. In this systematic review and meta-analysis, we aimed at investigating the efficacy and safety of intracoronary Pro-UK injection during PCI in ST elevation myocardial infarction (STEMI) patients. MATERIALS AND METHODS: A comprehensive literature searched on PubMed, Embase, Cochrane, Ovid-MEDLINE, Ovid-Embase, Ovid-Cochrane Databases and ClinicalTrials.gov from inception until June 1, 2022, in English only. The primary outcome was myocardial perfusion, including thrombolysis in myocardial infarction (TIMI) grades, corrected TIMI frame count (CTFC), TIMI myocardial perfusion grades (TMPG). The secondary outcomes were ST-segment resolution (STR), major adverse cardiovascular events (MACE), myocardial marker, cardiac function and hemorrhagic complications. RESULTS: We identified 5 studies (all RCTs) involving 761 participants. Under PCI procedure, compared with placebo, intracoronary Pro-UK injection may improve myocardial perfusion, including increasing the TIMI grades [odd ratio (OR) 0.46; 95% confidence interval (CI) 0.28-0.75; p = 0.002; I2 = 0%] , CTFC (OR -3.47; 95% CI [-5.60, -1.33]; p = 0.001; I2 = 0%) and TMPG (OR 0.17; 95% CI [0.06-0.44]; p = 0.0003; I2 = 0%), increase the rate of STR (OR 2.25; 95% CI [1.56-3.26]; p < 0.0001; I2 = 0%), reduce the incidence of MACE (OR 0.51; 95% CI [0.33-0.81]; p = 0.004; I2 = 0%) and reduce myocardial infarct size (CK, standardized mean difference [SMD] -0.45; 95% [CI] [-0.62, -0.28]; p < 0.00001; I2 = 10%. CK-MB, [SMD] -0.43; 95% CI [-0.68, -0.18]; p = 0.0007; I2 = 60%. cTnI, [SMD] -0.31; 95% CI [-0.46, -0.17]; p < 0.0001; I2 = 0%). Moreover, the treatment may improve the cardiac functions (LVFE, pooled mean difference [MD] 1.23; 95% CI [0.66-1.79]; p < 0.0001; I2 = 24%. LVEDd, pooled MD -0.13; 95% CI [-0.17, -0.09]; p < 0.00001; I2 = 0%). But there is no statistically significant difference between the Pro-UK group and placebo in the occurrence of hemorrhagic complications (OR 1.19; 95% CI [0.75-1.87]; p = 0.46; I2 = 0%). CONCLUSIONS: Intracoronary Pro-UK injection during PCI in STEMI patients is an effective and safe treatment to perform. The treatment may improve myocardial perfusion and rate of STR, as well as decreasing the incidence of MACE and myocardial infarct size. Importantly, the treatment may improve the cardiac functions and life quality. In the future, more multi-centered and massive sample studies are required.

[Family-based association tests for rare variants].

Next-generation sequencing has revolutionized family-based association tests for rare variants. As the lower power of genome wide association study for detecting casual rare variants, methods aggregating effects of multiple variants have been proposed, such as burden tests and variance component tests. This paper summarizes the methods of rare variants association test that can be applied for family data, introduces their principles, characteristics and applicable conditions and discusses the shortcomings and the improvement of the present methods.

[Advances in clinical research of virus vector-based COVID-19 vaccines].

The COVID-19 outbreak at the end of 2019 has accelerated the development and research for COVID-19 vaccines worldwide. Among the COVID-19 vaccines in clinical trials developed via different platforms, recombinant virus vector-based vaccines have shown excellent immunogenicity and efficacy. However, at the same time, there are serious issues such as vaccine safety and pre-existing antibodies against vectors. This article summarizes the design concept and development history of recombinant virus vector-based vaccines, and focuses on the progress in the clinical studies of vector-based COVID-19 vaccines as well as the challenges, in order to provide reference for the research of recombinant vector-based vaccines.

Burr hole craniostomy vs. minicraniotomy of chronic subdural hematoma: a systematic review and meta-analysis.

OBJECTIVE: Surgery is the mainstay of treatment for chronic subdural hematoma (CSDH). However, the best surgical method is still controversial. Three different methods including burr hole craniostomy (BHC), minicraniotomy (MC), and twist drill craniostomy (TDC) are commonly utilized. Besides, large craniotomy, trephine craniotomy [TC (single or double)], small craniotomy, and endoscopic removal are befittingly used in some situations, too. Hence, we performed a systematic review and meta-analysis to compare the effects between BHC and MC for surgical treatment in CSDH. MATERIALS AND METHODS: A literature research was conducted according to the PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies that directly compared BHC and MC for CSDH. The following endpoints were compared between BHC and MC: recurrence rate, reoperation rate, duration of operation, days of hospital treatment, postoperative complications, mortality, and rate of good outcome. RESULTS: Thirteen papers [n = 3,559 (3,580 operation sites), BHC: 1,936 operation sites, MC: 1,644 operation sites] met the inclusion criteria. The recurrence rate (OR: 0.56, 95% CI: 0.34-0.91, p = 0.02; I2 = 66%) was lower and the reoperation rate was also significantly lower (OR: 0.45, 95% CI: 0.25-0.81, p = 0.008; I2 = 72%) in the BHC group compared with the MC group. The duration of operation (MD: -20.15 min, 95% CI: -28.99 to -11.31, p < 0.00001; I2 = 0%) was significantly shorter in the BHC group compared with the MC group. Nevertheless, there was no statistically significant difference between the two groups in mortality (OR: 1.22, 95% CI: 0.92-1.61, p = 0.16; I2 = 38%), postoperative complications (OR: 0.68, 95% CI: 0.033-1.37, p = 0.28; I2 = 82%), days of hospital treatment (MD: 1.59, 95% CI: -10.44 to 13.62, p = 0.14; I2 = 85%) and rate of good outcome (OR: 1.40, 95% CI: 0.94-2.08, p = 0.10; I2 = 0%). CONCLUSIONS: A systematic review and meta-analysis of the included literature showed that BHC reduces the recurrence rate, reoperation rate and duration of operation compared to MC. BHC is much more minimal invasive when compared to MC. More invasions may signify more post-operative complications, which may cause the increasing rate of recurrence and reoperation. No significant difference in mortality, post-operative complications, days of hospital treatment and rate of good outcome was observed between the two groups.

Honey combined with silver ion dressing in complicated chronic wound of the scalp: a case report.

OBJECTIVE: Scalp wound healing is a complex process. Nonhealing wounds can become chronic wounds, which increase the trauma and economic burden on a patient and may even cause death in severe cases. Thus, it can be difficult to find an effective treatment for chronic wounds of the scalp. CASE PRESENTATION: We present a case of a 13-year-old female patient with a chronic wound caused by a scalp incision infection 3 months after two operations for craniotomy for arachnoid cyst resection and cystic lesion-cisterna magna drainage. After repeated dressing changes and two debridement operations, the incision had still not healed during the following year. The wound finally healed after 6 months of dressing changes by combining honey with silver ion dressings, and the incision had not re-ruptured after 10 months of follow-up. CONCLUSIONS: Honey combined with silver may be an effective method for the treatment of chronic scalp wounds.

[Early German research on virology and establishment of the specialised research institution].

Aftosa spread rapidly in Europe at the end of the 19th century.The German imperial government was concerned about it and appointed some scientists, such as Friedrich Loeffler and Paul Frosch, to do the research on it and they identified the virus of Aftosa in 1897. An experimental study was planned to be conducted by Friedrich Loeffler at the Greifswald Institute of Hygiene at a farm outside the city in 1899, but cancelled by the Government concerned about potential safety hazards in the research sites. After three years of preparation, the first virology research institution in the world was established by Friedrich Loeffler and others on Riems Island in Germany on October 10, 1910. This old virology research institution has now become the Federal Animal Health Research Center, making significant contributions to human research on zoonotic diseases.

Local anesthesia with sedation and general anesthesia for the treatment of chronic subdural hematoma: a systematic review and meta-analysis.

OBJECTIVE: Drilling and drainage is the main treatment for chronic subdural hematoma (cSDH). However, anesthesia methods also have an important effect on patients' postoperative outcomes. The clinical effect of drainage of cSDH under local anesthesia with sedation (LAS) and general anesthesia (GA) was systematically evaluated. MATERIALS AND METHODS: A literature study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies that compare LAS and GA for cSDH. The following treatment outcomes were compared between LAS and GA: total duration of surgery, postoperative complications, mortality, recurrence rate, and hospital length of stay (LOS). RESULTS: Four papers (n = 391, LAS: 196, GA: 195) met the inclusion criteria. Although there was no statistically significant difference between the two groups in mortality (OR: 0.47, 95% CI: 0.06-3.84, p = 0.48; p = 0.2, I2 = 39%), recurrence rate (OR: 0.82, 95% CI: 0.33-2.04, p = 0.66; p = 0.69, I2 = 0%), LOS (ratio of means: 0.86, 95% CI: 0.71-1.05, p = 0.14; p = 0.02, I2 = 75%). The total duration of surgery (MD: -26.71 min, 95% CI: -37.29 to -16.13, p < 0.00001; p = 0.65, I2 = 0%) was significantly shorter and the number of postoperative complications was significantly lower in the LAS group compared with the GA group (OR: 0.25, 95% CI: 0.13-0.50, p < 0.0001; p= 0.62, I2 = 0%). CONCLUSIONS: A systematic review and meta-analysis of the existing literature showed that LAS reduces the total duration of surgery and postoperative complications compared to GA. No significant difference in mortality, recurrence rate, and LOS was observed between the two groups.

Association of the stress hyperglycemia ratio and clinical outcomes in patients with cardiovascular diseases: a systematic review and meta-analysis.

OBJECTIVE: Cardiovascular disease (CVD) and cerebrovascular disease are the leading cause of death around the world all the time. A novel marker described as the stress hyperglycemia ratio (SHR) can reflect the acute hyperglycemic status and is associated with poor outcomes in patients with acute illness, such as stroke and myocardial infarction (MI). Our previous study has shown that SHR was strongly related to the clinical outcomes of stroke patients. Nevertheless, the association between SHR and clinical outcomes in patients with CVD is still unclear and controversial. Consequently, in the current study, we analyzed the association of SHR and clinical outcomes in CVD patients by systematic review and meta-analysis. MATERIALS AND METHODS: We searched the electronic databases to identify SHR studies of patients who met the eligibility criteria for CVD. We performed our study complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We utilized a ten terms tool to assess the potential bias of included studies. Major adverse cardiovascular and cerebrovascular events (MACCEs), all-cause death, left ventricular ejection fraction (LVEF), and other exciting outcome data were extracted for statistical analysis. Moreover, we used the DerSimonian and Laird random-effects model to perform the meta-analysis and conducted subgroup analyses to identify factors associated with substantial heterogeneity. RESULTS: The study cohort included nine studies comprising 32,292 patients with CVD. Our meta-analysis found that MACCEs in the high SHR group were 1.68 folds compared with that in the low SHR group [odds ratio (OR) 1.68, 95% confidence interval (CI) 1.41-2.00, p < 0.00001]. Besides, all-cause death in the high SHR group was 1.52 folds compared with that in the low SHR group (OR 1.52, 95% CI 1.15-2.01, p < 0.00001). Higher SHR meant the lower LVEF (mean difference [MD] -2.03, 95% CI [-3.28-0.79], p = 0.001). The risk of cardiogenic shock and stroke were 2.47 and 1.53 folds in the high SHR group, respectively, compared with the low SHR group. Yet, no statistically significant difference was observed for revascularization (OR 0.88, 95% CI 0.77-1.01, p = 0.08), recurrent MI (OR 1.27, 95% CI 0.69-2.33, p = 0.44), and left ventricular end-diastolic diameter (LVEDD) (MD 0.61, 95% CI [-1.65, 2.87], p = 0.60) between the two groups. Subgroup analyses identified that different study design was associated with heterogeneity about MACCEs and LVEF. Besides, studies from different countries were associated with heterogeneity about all-cause death. CONCLUSIONS: Higher SHR significantly increases the occurrence of MACCEs and all-cause death and decreases LVEF. Moreover, Higher SHR means a higher risk of cardiogenic shock and stroke. Nevertheless, SHR had no relationship with revascularization, recurrent MI, and LVEDD. As a novel and non-invasive marker, SHR should be paid more attention to in clinical practice. Future investigation should focus on the diagnostic value of SHR in CVD and the early control of stress hyperglycemia. Although no randomized, double-blind studies have been conducted, the available massive sample studies reflect the actual situation in the clinic and assist clinical decision-making.

[ALPK3 gene-related pediatric cardiomyopathy with craniofacial-skeletal features: a report and literature review].

Objective: To explore the clinical characteristics and mutation spectrum of ALPK3-related pediatric cardiomyopathy and craniofacial-skeletal abnormalities in children. Methods: The clinical data during a follow-up of 11 years including clinical features, echocardiogram, electrocardiogram, cardiac magnetic resonance, genetic testing, and other data of a child firstly diagnosed with ALPK3 gene-related cardiomyopathy and craniofacial-skeletal abnormalities in China were collected retrospectively. The literatures containing the keyword of "ALPK3 gene" published in the China National Knowledge Infrastructure, Wanfang database and PubMed were collected up to November 2020. Then, the clinical features and gene mutations of ALPK3 gene-related pediatric cardiomyopathy with craniofacial-skeletal features were summarized. Results: A female patient aged 10 months who presented with an enlarged heart for 2 months, was admitted to the hospital and initially diagnosed with endocardial elastic fibrosis. The echocardiography showed features of dilated left ventricle (LV) and LV systolic dysfunction. Low-set ears, webbed neck, a grade 2/6 systolic murmur at lower left sternal area and bilateral absent flexion creases of dig were observed. After treatment, the size and function of the heart recovered to normal at age 13 months. However, the ventricular septum and LV wall were thicker than normal values. Then, the diagnosis was revised to hypertrophic cardiomyopathy(HCM) and suspected congenital malformation syndrome. LV hypertrophy (LVH) progressed slowly before the age of 8 years and then progressed rapidly. At age 9 years, compound heterozygous ALPK3 mutations (c.721dup, p.Y241Lfs*42(exon 1) and c.4840C>T, p.R1614*(exon 10)) were detected in the proband and the mutations had not been reported previously. Then, the final diagnosis of ALPK3 gene-related pediatric cardiomyopathy with craniofacial-skeletal features was made. During the follow up of 11 years, regular follow-up echocardiographic images showed progressive LVH. At age 11 years, electrocardiogram showed LVH, ST-T changes in multiple-lead, T wave inversion, and prolonged QT intervals. Cardiac magnetic resonance showed biventricular hypertrophy and late gadolinium enhancement showed non-uniform enhancement of left and right ventricular myocardium. A total of 7 articles published in English were retrieved, and no Chinese literature was found. Twenty-eight cases were reported in the articles plus the patient in this study. Twenty-four mutations were reported worldwide, 18 patients carried homozygous mutations and 10 patients compound heterozygous mutations. Eleven patients showed dilated cardiomyopathy (DCM) at early stage of disease, and 10 of them transitioned to HCM at the disease progression stage. Eight patients presented with HCM at early stage of disease. Nine patients initially exhibited a mixed phenotype of DCM and HCM, and 6 of them eventually progressed to HCM. Electrocardiogram showed prolonged QT interval. Extracardiac features included short stature, special face, cleft palate, webbed neck, joint contracture, and scoliosis, etc. Conclusions: Progressive myocardial hypertrophy is a major feature of ALPK3 gene-related cardiomyopathy with craniofacial-skeletal malformations. Precise diagnosis depends on molecular genetic techniques. More cases should be accumulated for further analysis on the genotype-phenotype correlation and prognosis assessment.

[The development history of oral contraceptives].

The creation of oral contraceptives goes back 60 years. It has gone through a long and complex process from the discovery of sex hormones to their development into drugs to market. A correct understanding of the developmental history of oral contraceptives is of great importance for human reproduction. Gregory G Pincus successfully synthesized the first oral contraceptive Enovid based on research by Carl Djerassi, this was approved for marketing by the US Federal Drug Administration (FDA) in May 1960. However, due to the severe side effects of Enovid, the safer and more effective second generation oral contraceptives - Levonorgestrel and the third generation oral contraceptives - Pregnene are widely used and continue to be used to this day. The introduction of oral contraceptives not only dampened the explosive growth of the world's population, but also improved the social status of women, and catalyzed the sexual liberation movement.

The association of serum Kallikrein-8 with cognitive function in vascular dementia.

OBJECTIVE: Kallikrein-8 (KLK8) is a secreted serine protease related to learning and memory. Evidence has confirmed the important role of KLK8 in neuroplasticity. However, the role of KLK8 in vascular dementia (VaD) is unclear. PATIENTS AND METHODS: The study recruited 88 VaD patients and 72 normal controls. All subjects were tested for cognitive function by Mini-Mental State Examination (MMSE) upon admission, and their demographic and biochemical data were collected. A sandwich Enzyme-Linked Immunosorbent Assay (ELISA) test was used to detect serum KLK8 levels. The demographic and biochemical data of the two groups of subjects were compared. Spearman's correlation and multivariate regression analysis were used to determine whether serum KLK8 in VaD patients is a risk factor for cognitive function. RESULTS: A total of 88 VaD patients and 72 controls with normal cognitive function were recruited and divided into VaD group and control group. Except for TT3 (p=0.002), there was no statistically significant difference in other demographic and biochemical data between the two groups (p>0.05). The results of ELISA indicated that the serum KLK8 in VaD patients was significantly higher than that of the control population (p<0.001). Spearman correlation analysis indicated that the serum KLK8 in VaD was significantly inversely correlated with the MMSE score. The results of Spearman's correlation analysis showed that the serum KLK8 level of VaD was significantly inversely correlated with the MMSE (r=-0.305, p=0.017). After correcting for interference factors, the correlation between the two is still significant (ß=0.398, p=0.024). CONCLUSIONS: Serum KLK8 may be an independent risk factor affecting the cognitive function of VaD, which is worthy of further research.