Terpine-4-ol is abundant in nature. As a cyclic monoterpenoid compound， terpine-4-ol is distributed in a variety of natural plants. It is the main component and the key active substance in many traditional Chinese essential oils， such as Melaleuca alba essential oil and coral ginger essential oil. Terpine-4-ol has anti-microbial， anti-tumor， insecticidal， anti-inflammatory， and other effects. It can treat cancer， as well as oral and cardiovascular diseases with great safety. In terms of antibacterial activity， terpine-4-ol can destroy bacterial cell walls， improve membrane permeability， and regulate bacterial migration， reproduction， and other related genes to inhibit bacterial activity. In terms of antifungal activity， terpine-4-ol can bind with ergosterol in fungal cell walls to cause fungal death. In terms of insecticidal activity， terpine-4-ol can inhibit Na⁺ and K⁺-ATPase activity and cause the death of the insect. In terms of anticancer activity， terpine-4-ol can regulate the expression of apoptosis-related proteins in cancer cells， so as to control the apoptosis of cancer cells. In this paper， the pharmacological activity and action mechanism of terpine-4-ol were reviewed to provide a reference for further research and utilization of terpine-4-ol.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Objective: To understand the relationship between secondhand smoke exposure and dyslipidemia among adults in Beijing and to provide a scientific basis for relevant intervention. Methods: Data were from Beijing Adult Non-communicable and Chronic Diseases and Risk Factors Surveillance Program in 2017. A total of 13 240 respondents were selected by multistage cluster stratified sampling method. The monitoring contents include a questionnaire survey, physical measurement, collection of fasting venous blood, and determination of related biochemical indicators. SPSS 20.0 software was used for the chi-square test and multivariate logistic regression analysis. Results: The prevalence of total dyslipidemia (39.27%), hypertriglyceridemia (22.61%), and high LDL-C (6.03%) were the highest among those exposed to daily secondhand smoke. Among the male respondents, the prevalence of total dyslipidemia (44.42%) and hypertriglyceridemia (26.12%) were the highest among those exposed to secondhand smoke daily. Multivariate logistic regression analysis after adjustment for confounding factors showed that compared with no exposure to secondhand smoke, the population with an average exposure frequency of 1-3 days per week had the highest risk of total dyslipidemia (OR=1.276, 95%CI: 1.023-1.591). Among the patients with hypertriglyceridemia, those exposed to secondhand smoke daily had the highest risk (OR=1.356, 95%CI: 1.107-1.661). Among the male respondents, those exposed to secondhand smoke for 1-3 days per week had a higher risk of total dyslipidemia (OR=1.366, 95%CI: 1.019-1.831), and the highest risk of hypertriglyceridemia (OR=1.377, 95%CI: 1.058-1.793). There was no significant correlation between the frequency of secondhand smoke exposure and the risk of dyslipidemia among female respondents. Conclusions: Secondhand smoke exposure in Beijing adults, especially men, will increase the risk of total dyslipidemia, especially hyperlipidemia. Improving personal health awareness and minimizing or avoiding exposure to secondhand smoke is necessary.
Adult ; Humans ; Female ; Male ; Tobacco Smoke Pollution/adverse effects* ; Beijing ; Dyslipidemias/epidemiology* ; Hypertriglyceridemia/epidemiology* ; Fasting

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

The male patient was referred to the hospital at 44 days old due to dyspnea after birth and inability to wean off oxygen. His brother died three days after birth due to respiratory failure. The main symptoms observed were respiratory failure, dyspnea, and hypoxemia. A chest CT scan revealed characteristic reduced opacity in both lungs with a "crazy-paving" appearance. The bronchoalveolar lavage fluid (BALF) showed periodic acid-Schiff positive proteinaceous deposits. Genetic testing indicated a compound heterozygous mutation in the ABCA3 gene. The diagnosis for the infant was congenital pulmonary alveolar proteinosis (PAP). Congenital PAP is a significant cause of challenging-to-treat respiratory failure in full-term infants. Therefore, congenital PAP should be considered in infants experiencing persistently difficult-to-treat dyspnea shortly after birth. Early utilization of chest CT scans, BALF pathological examination, and genetic testing may aid in early diagnosis.
Infant ; Infant, Newborn ; Humans ; Male ; Bronchoalveolar Lavage/adverse effects* ; Pulmonary Alveolar Proteinosis/pathology* ; Dyspnea/etiology* ; Respiratory Insufficiency

Immune checkpoints (ICs) are immunosuppressive molecules expressed on immune cells, which can regulate immune cells' activation. Immune checkpoint inhibitors (ICIs) which can block the interaction of immune checkpoints and their ligands, improve the cytotoxic effect of the immune system on tumor cells. Immunotherapy such as employing ICIs has gradually become a conventional therapeutic strategy for cancer treatment. However, the low response rate and the emergence of drug resistance have seriously affected the clinical efficacy of ICIs. Reactive oxygen species (ROS) are electronic reduction products of active oxygen, as well as natural by-products of cell metabolism, which can be used as regulators of intercellular signals. Tumor microenvironment (TME) is often in the state of oxidative stress (OS), which is the imbalance between oxidative system and antioxidant system. ROS can affect the interaction with its ligands by regulating the expression and activity of immune checkpoints in TME, thus affecting the anti-tumor effect of immune cells. Accumulating studies have shown that ROS could regulate tumor immune checkpoints through several pathways. Due to different types and stages of tumor, it would be clinical beneficial to understand the mechanistic link of ROS on tumor immune checkpoint, and choose appropriate ROS regulators combined with immune checkpoint inhibitors to maximize anti-tumor effects. This article reviews the common metabolic sources and characteristics of ROS, the regulatory effect and mechanism of ROS on tumor immune checkpoints and its therapeutic application.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective: To evaluate the efficacy of the Hodgkin lymphoma (HL)-2013 regimen in the treatment of children with HL, and to investigate the prognostic factors of childhood HL. Methods: Clinical data of 145 children (aged ≤18 years) with newly diagnosed HL, treated with HL-2013 regimen in 8 tertiary referral centers for childhood cancer from August 2011 to April 2021 were analyzed retrospectively. All the diagnosis were confirmed by histopathological morphology and immunohistochemical examination. The clinical characteristics and treatment outcomes were summarized, and the patients were divided into different groups according to clinical characteristics. Kaplan-Meier method was used for survival analysis, and the comparison of survival rates between groups was performed with Log-rank test. Results: Of the 145 cases, there were 115 males and 30 females, the age at diagnosis was 7.9 (5.8, 10.6) years. Cervical lymph node enlargement (114 cases, 78.6%) was the common symptom of the disease, and 57 patients (39.3%) were accompanied by large masses. The most common pathological classification was mixed cell type (93 cases, 64.1%). According to the Ann Arbor staging system, there were 9 cases of stage Ⅰ, 62 cases of stage Ⅱ, 45 cases of stage Ⅲ, 29 cases of stage Ⅳ. According to the risk stratification: there were 14 cases of low-risk group, 76 cases of medium-risk group and 55 cases of high-risk group. Of all patients, 68 cases (46.9%) achieved an early complete remission (CR) after 2 courses of chemotherapy, and the CR rate was 93.8% (136/145) after first-line treatment. Disease recurrence or progression occurred in 22 cases (15.2%). Of all patients, 125 cases survived, 6 cases died and 14 cases were lost to follow-up. Among the survived cases, 123 cases were continuously at CR state,and the follow-up time was 55 (40, 76) months. The 5-year overall survival (OS) and event free survival (EFS) rates were (95.3±1.9)% and (84.2±3.0)% for the entire group, respectively. 5-year OS and EFS rates for patients with stage Ⅲ-Ⅳ were both lower than those for patients with stage Ⅰ-Ⅱ (χ²=6.28 and 7.58, both P<0.05), the 5-year OS and EFS rates for patients in high-risk group were both lower than those for patients in low-risk and medium-risk group (χ²=10.93, 7.79, both P<0.05). The 5-year OS rates for the patient with early CR and without early CR were 100.0% and (90.9±3.6)% (χ²=5.77, P=0.016). EFS rates for the patient with early CR (68 cases) and without early CR (77 cases) were (93.8±3.0)% and (75.8±5.0)% (χ²=8.78, P=0.003). Conclusions: HL-2013 regimen is significantly effective in the treatment of pediatric HL. However, the patients in high-risk group and those without early CR are prone to disease recurrence or progression. Stage Ⅲ-Ⅳ and without early CR were associated with worse prognosis.
Child ; Female ; Male ; Humans ; Hodgkin Disease ; Retrospective Studies ; Neoplasm Recurrence, Local ; China ; Antineoplastic Combined Chemotherapy Protocols ; Prognosis ; Disease-Free Survival

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.
China ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Prescriptions ; Public Health

Neoadjuvant chemotherapy (NAC) has shown promising results in patients with locally advanced penile cancer. However, no consensus exists on its applications for locally advanced penile cancer. Thus, it is unclear which kind of chemotherapy regimen is the best choice. Consequently, a systematic search of PubMed, Web of Science, and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer. The Newcastle-Ottawa Scale was used to assess the risk of bias in each study. This study synthesized 14 published studies. The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response. In addition, the objective response rates (ORRs) and pathological complete response (pCR) rates were 0.57 and 0.11, respectively. The incidence of grade ≥3 toxicity was 0.36. Subgroup analysis found that the ORR and pCR of the taxane-platinum (TP) regimen group performed better than those of the nontaxane-platinum (NTP) regimen group (0.57 vs 0.54 and 0.14 vs 0.07, respectively). Moreover, the TP regimen group had more frequent toxicity than the NTP regimen group (0.41 vs 0.26). However, further studies were warranted to confirm the findings.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Humans ; Male ; Neoadjuvant Therapy/methods* ; Penile Neoplasms/drug therapy* ; Platinum ; Treatment Outcome