In recent years,the development of acupuncture and moxibustion(shortened as acup-moxibustion)has flourished.With the verification of clinical efficacy of acup-moxibustion,its basic research has gradually drawn the attention of the practitioners accordingly.But how to scientifically perform the basic research of acup-moxibustion and to serve the clinic effectively has become a major problem for the contemporary Chinese medicine practitioners.By analyzing the characteristics of acup-moxibustion-related research projects funded by the National Natural Science Foundation of China,this paper outlined the current status of domestic research of acup-moxibustion,and proposed four suggestions after analyzing the problems and weaknesses of acup-moxibustion basic research in China:①the clinical evidence-based system in the current acup-moxibustion should be further constructed and the basic research should be focused on the area of advantages;② the key problems of acup-moxibustion basic research should be clarified,and the proportion of original researches should be increased;③ the integration of production,teaching and research of acup-moxibustion should be enhanced to adapt to the era of big science;④ the funding system and its polity and structure needed to be reformed.This study will help to increase the discipline ranking of acup-moxibustion,enhance its high-quality development,and promote its internationalization.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To investigate the effect of exosomes loaded with Lycium barbarum miRNA(Lb-miR2911)on spermato-genic function recovery in non-obstructive azoospermia(NOA)rats through cross-regulation of the Wnt/β-catenin signaling pathways.Methods:We established an NOA model in 30 four-week-old male SD rats by intraperitoneal injection of busulfan.At 5 weeks after modeling,we equally randomized the rats into a model control group(MC,untreated),an Lb-miR2911EXO group(Lb-miR2911EXO,treated by intratesticular injection of Lb-miR2911-loaded exosomes),and a sham group(Shame,treated by intratesticular injection of exosomes-empty drug),with another 10 male SD rats taken as normal controls(NC).We observed the uptake and metabolic changes of Lb-miR2911 in the testis tissue of the rats by RNA FISH at 2 and 6 weeks after treatment,detected cell proliferation,spermatogenesis and gene expressions of the Wnt/β-catenin signaling pathways in the testis tissue by Transcriptome sequencing analysis combined with Western blot and RT-PCR at 12 weeks,evaluated the recovery of the spermatogenic function based on the testis tissue morphology and sperm quality,and assessed the organ toxicity of Lb-miR2911 in the tissue and organs of the rats based on histomorphological analysis and the levels of serum TNF-α,IL-1β,Aspartate aminotransferase(AST),Alanine aminotransferase(ALT)and other relevant indi-cators.Results:After 12 weeks of treatment,histomorphological analysis showed regular arrangement of spermatogenic cells at all levels in the testis tissue,with a large number of mature sperm in the tubular lumen,and with significantly higher Johnsen scores,tes-tis weight,testicular index,sperm concentration and sperm motility in the Lb-miR2911EXO than in the sham group(all P<0.05).Compared with the model controls,the Lb-miR2911EXO group exhibited remarkably down-regulated gene expression of DACT3(P<0.05),up-regulated expressions of DVL2 and β-catenin(P<0.05),elevated levels of p-DVL2 and β-catenin(nucleus)proteins(P<0.05),increased expressions of cell proliferation-related genes CCND1,CCNE1 and CCNE2(P<0.05)and spermatogenesis-related genes DMC1,CCR6,JAM2 and KLC3(P<0.05).No pathological changes were observed in the lung,liver and kidney tis-sues of the rats,or in the levels of serum TNF-α,IL-1β,AST,ALT,creatinine and urea nitrogen in the rats treated with Lb-miR2911EXO compared with the normal controls(P>0.05).Conclusion:Lb-miR2911-loaded exosomes promote spermatogenic function recovery in NOA rats through cross-regulation of the DACT3,Wnt and β-catenin signaling pathways.

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: SET8 is a member of the SET domain-containing family and the only known lysine methyltransferase (KMT) that monomethylates lysine 20 of histone H4 (H4K20me1). SET8 has been implicated in many essential cellular processes, including cell cycle regulation, DNA replication, DNA damage response, and carcinogenesis. There is no conclusive evidence, however, regarding the effect of SET8 on radiotherapy. In the current study we determined the efficacy of SET8 inhibition on radiotherapy of tumors and the underlying mechanism. Methods: First, we explored the radiotherapy benefit of the SET8 expression signature by analyzing clinical data. Then, we measured a series of biological endpoints, including the xenograft tumor growth in mice and apoptosis, frequency of micronuclei, and foci of 53BP1 and γ-H2AX in cells to detect the SET8 effects on radiosensitivity. RNA sequencing and subsequent experiments were exploited to verify the mechanism underlying the SET8 effects on radiotherapy. Results: Low expression of SET8 predicted a better benefit to radiotherapy in lung adenocarcinoma (LUAD) and invasive breast carcinoma (BRCA) patients. Furthermore, genetic deletion of SET8 significantly enhanced radiation treatment efficacy in a murine tumor model, and A549 and MCF7 cells; SET8 overexpression decreased the radiosensitivity. SET8 inhibition induced more apoptosis, the frequency of micronuclei, and blocked the kinetics process of DNA damage repair as 53BP1 and γ-H2AX foci remained in cells. Moreover, RNF8 was positively correlated with the SET8 impact on DNA damage repair. Conclusion Our results demonstrated that SET8 inhibition enhanced radiosensitivity by suppressing DNA damage repair, thus suggesting that SET8 potentiated radiotherapy of carcinomas. As new inhibitors of SET8 are synthesized and tested in preclinical and clinical settings, combining SET8 inhibitors with radiation warrants consideration for precise radiotherapy.
Animals ; Apoptosis ; Carcinogenesis ; Carcinoma/radiotherapy* ; Cell Cycle ; Cell Line, Tumor ; DNA Damage ; DNA Replication ; HeLa Cells ; Histone-Lysine N-Methyltransferase ; Humans ; Mice ; Radiotherapy

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

ObjectiveTo analyze the chemical composition of the reference sample of Huangqi Guizhi Wuwutang （lyophilized powder）， and to provide quality markers for the formulation of quality standards of this formula. MethodUltra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS） was performed on a Waters ACQUITY UPLC™ HSS T3 column （2.1 mm×100 mm， 1.8 μm）， the mobile phase was methanol （A） -0.1% formic acid aqueous solution （B） for gradient elution （0-8 min， 1%-20%A； 8-10 min， 20%-30%A； 10-12 min， 30%-35%A； 12-14 min， 35%-40%A， 14-23 min， 40%-55%A， 23-27 min， 55%-99%A； 27-28 min， 99%A； 28-28.5 min， 99%-1%A； 28.5-30 min， 1%A）， the column temperature was 40 ℃， the injection volume was 2 μL， and the flow rate was 0.3 mL·min^-1. The mass spectrometry data of the reference sample of Huangqi Guizhi Wuwutang （lyophilized powder） were collected under positive and negative ion modes. The conditions of mass spectrometry were electrospray ionization （ESI）， scanning range of m/z 50-1 200， and impact energy of 10-30 eV. UNIFI 1.8 and Progenesis QI 2.0 software were used to analyze and characterize the chemical constituents in reference sample of Huangqi Guizhi Wuwutang （lyophilized powder） combined with reference comparison and literature review. ResultA total of 123 chemical constituents were identified， including 33 flavonoids， 26 glycosides， 18 organic acids， 11 terpenoids， 7 phenylpropanoids， 4 gingerol， 3 alkaloids， 3 amino acids， 2 amides and 16 other compounds. ConclusionThe established method can quickly and accurately characterize the chemical components in the reference sample of Huangqi Guizhi Wuwutang （lyophilized powder）， which can provide a basis for the selection of quality evaluation indicators of this formula， and provide a reference for its preparation research.

The decline of body function and senile diseases caused by aging seriously affect human health and life span， which is an important topic in the field of life science. Bazi Bushen capsules is a representative Chinese patent medicine for tonifying essence， invigorating Qi and anti-aging， guided by Qiluo doctrine， and essence， Qi and spirit theory. Previous pharmacological and clinical studies have confirmed that this preparation has the comprehensive advantages of anti-aging， and prevention and treatment of aging-related diseases. Among them， pharmacological studies showed that Bazi Bushen capsules had the effect of improving the appearance status of mice， improving the level of sex hormones， inhibiting the formation of atherosclerosis， improving cardiac function， improving learning and memory cognitive ability， improving neurological function， improving osteoporosis and muscle function， improving sperm count and quality. The mechanism was related to the up-regulation of the recombinant sirtuin （SIRT6） level， down-regulation of the levels of aging-related proteins p53 and p16， up-regulation of telomerase reverse transcriptase level， and alleviation of inflammation and oxidative response. Clinical studies have proved that it can improve the symptoms of patients with kidney essence deficiency， improve exercise ability， and improve the sexual function of impotence patients. Anti-aging research of Bazi Bushen capsules based on Qiluo doctrine fully embodies the new mode of academic innovation and transformation of traditional Chinese medicine （TCM） with the combination of "theory-new drug-experiment-clinic"， which has made a demonstration for the anti-aging research of TCM.

OBJECTIVE: To investigate the association between serum high sensitivity C-reaction protein (hsCRP) in early pregnancy and gestational diabetes mellitus (GDM) among twin pregnant women, and to explore the effects of the pre-pregnant body mass index (BMI) and gestational weight gain (GWG) status on such association. METHODS: Twin pregnant women with pre-pregnant BMI greater than or equal to 18.5 kg/m² were recruited at Department of Obstetrics and Gynecology of Peking University Third Hospital from March 2017 to December 2020. Serum samples collected in early pregnancy were analyzed for hsCRP using particle-enhanced immunoturbidimetric method. In the following visits, the information about GWG and GDM were prospectively collected in every trimester. The association effect between hsCRP tertiles and GDM were estimated using Logistic regression, and further converted into risk ratio (RR). Cochran-Mantel-Haenszel test and mediation analysis were used to explore the effects of BMI and GWG status on the association. RESULTS: Among the included 570 twin pregnant women, 31.6% deve-loped GDM, 26.1% were pre-pregnant overweight or obesity, and 49.5% with GWG out of referenced range. After adjustment for confounding factors, risk of developing GDM in twin gestations with the middle tertile and highest tertile of serum hsCRP in early pregnancy were 1.42 fold (95%CI: 1.02-1.89) and 1.54 fold (95%CI: 1.12-2.02), respectively, compared with the lowest tertile of serum hsCRP, and there existed significantly linear trend (P=0.022). Findings from mediation analysis illustrated that pre-pregnant BMI had partial mediating effect on the association, and BMI accounted for 23.84% (P < 0.001) of the increasing GDM risks with elevated hsCRP. Joint analysis with hsCRP and GWG found that those who were with GWG out of referenced range accompanied with the higher hsCRP tertiles (>1.21 mg/L) had significantly 2.31 fold increased risk according to those who were with GWG in the referenced range accompanied with the lowest hsCRP tertile (≤1.21 mg/L, P < 0.01). CONCLUSION Elevated hsCRP in early pregnancy significantly increased GDM risk among twin pregnant women. The hsCRP-GDM association was dependent on GWG status, and pre-pregnant BMI had partial mediating effect on such association. It is suggested that twin pregnant women should consider systemic inflammation and gestational weight at the same time to reduce GDM risk.
Body Mass Index ; C-Reactive Protein/metabolism* ; Cohort Studies ; Diabetes, Gestational/blood* ; Female ; Gestational Weight Gain ; Humans ; Pregnancy ; Pregnancy, Twin/blood* ; Weight Gain

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