[Clinical study of immune-targeting combined with attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma].

Objective: To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL). Methods: A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×106/L and was 12 (0, 25)×106/L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion: BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.

Hematoporphyrine injection-based photodynamic therapy for Perianal Paget's disease: A case report.

Paget's disease of the perianal skin (PPD) is a rare form of extramammary Paget's disease, which can manifest as either a primary intraepithelial adnexal neoplasm or as a secondary condition resulting from the spread of an underlying colorectal lesion. Surgical resection is the primary treatment for PDD, but it poses risks to the aesthetic appearance and functional integrity of the anus. Moreover, its clinical application is limited, particularly in cases of lesions present in multiple skinfold areas, multiple and recurrent lesions, extensive lesion areas, or in elderly patients with poor health. Hematoporphyrin derivative photodynamic therapy (HpD-PDT) serves as an alternative treatment for patients who are not suitable candidates for surgery and for conditions characterized by extensive and discontinuous disease. Here, we present the case of a 70-year-old man with PPD, presenting perianal skin lesions extending beyond the dentate line into the anal canal. When considering HpD-PDT, it is essential to take into account the preservation of function, patient preferences, and potential adverse effects. Subsequent to HpD-PDT, the lesion was effectively eradicated, and anal function was preserved without any notable proliferative, atrophic scarring, or other side effects. Therefore, HpD-PDT proves to be an effective treatment for PPD, offering aesthetic improvement, minimal functional disruption, and a high level of tolerability.

[Analysis of pollution status and influencing factors of polybrominated diphenyl ethers in household dust in five cities in northern China].

Objective: To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China. Methods: Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust. Results: The M (Q1, Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑12PBDEs in Luoyang and Shijiazhuang (P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ß (95%CI): 0.186 (0.013, 0.359)], infrequent home cooking [ß (95%CI):-0.342 (-0.570, -0.114)], and increased residential PM10 concentration [ß (95%CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ß (95%CI): 0.093 (0.013, 0.172)], house area less than 90 m2 [ß (95%CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ß (95%CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑12PBDEs in household dust. Conclusion: The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

[Primary ciliary dyskinesia associated with a novel DNAH11 genetic variant: a case report].

Primary ciliary dyskinesia (PCD) is a heterogeneous genetic disorder associated with abnormalities in ciliary structure and function. Here, we report A 22-year-old non-smoking Chinese man with recurrent episodes of respiratory tract infections and sinusitis since high school period. The diagnosis is more complicated by the atypical symptoms and the late age of onset. We summarized the clinical characteristics of this case and literature review. This report aimed to improve the clinical understanding of primary ciliary dyskinesia.

Effects of fermented and unfermented aging corn on ruminal fermentation, bacterial communities, lactation performance and plasma metabolites in Holstein cows.

Aging reduces the nutritional value of corn grain, which may be improved by fermentation prior to use. This study investigated the effects of replacing conventional corn (CC) with aging corn (AC) and fermented aging corn (FAC) in the diets of lactating Holstein cows. Six healthy third-parity Holstein cows were used in a replicated 3 × 3 Latin square experiment with 21-day periods. Cows were fed twice and milked twice daily. The cows were randomly divided into three treatment groups: (1) CC diet: a diet with 23.6% starch in diet DM containing 24.0% conventional corn; (2) AC diet: a diet with 23.5% starch in diet DM containing 24.0% aging corn replacing conventional corn; and (3) FAC diet: a diet with 23.2% starch in diet DM containing 24.6% fermented aging corn replacing conventional corn. The diets were formulated to be isonitrogenous and contained identical roughage. The FAC treatment increased the starch digestibility compared with AC. Feeding FAC increased the concentrations of total volatile fatty acid compared with CC and AC and decreased the molar proportion of acetate compared with AC. At the family level, the relative abundance of Prevotellaceae was higher on FAC than CC. The relative abundance of Succinivibrionaceae was lower on FAC than on CC and AC. Besides, at the genera level, the relative abundance of Succinivibrionaceae_UCG_002 in the rumen was higher on AC than CC and FAC. The relative abundance of Prevotella and Ruminococcus was higher on FAC than CC and AC. The relative abundance of Succinivibrionaceae_UCG_001 was lower on FAC than CC. The Simpson index was lower on FAC than CC and AC. The FAC treatment increased the milk yield (34.0, 33.7, and 35.2 kg/d for CC, AC, and FAC group, respectively) and protein yield, and thus, energy-corrected milk production was increased, and at the same time, decreased the somatic cell score compared with CC and AC. The AC treatment increased the malondialdehyde concentration in plasma compared with CC and FAC. The concentrations in plasma of triglyceride and malondialdehyde were lower on FAC than AC. The immunoglobulin G concentration in plasma was higher on FAC than CC and AC. Overall, feeding AC resulted in decreased plasma antioxidant capacity compared with CC, whereas feeding FAC altered the relative abundance of bacteria in the rumen and improved starch digestibility, ruminal bacterial diversity, lactation performance, plasma antioxidant capacity and immune competence compared with AC in dairy cows.

[Efficacy and safety of dienogest on ovarian endometrioma].

Objective: To observe the effects and safety of dienogest on the volume and symptoms of ovarian endometrioma (OMA). Methods: The clinical data of 75 patients with OMA who underwent treatment with dienogest (2 mg/day) at the First Affiliated Hospital of Nanjing Medical University from July 1st 2020 to March 31st 2024 were retrospectively analysed, mainly comparing the changes in the volume of OMA and the visual analogue scale (VAS) scores of endometriosis-related pain before and after the treatment, as well as observing the changes in the blood biological indicators, liver and kidney function, coagulation function and changes in breast. Results: The median cyst volumes of the OMA patients at 3, 6 and 12 months of dienogest treatment were 13.21 cm3 (volume reduction rate: 36.00%), 8.33 cm3 (volume reduction rate: 56.00%) and 4.10 cm3 (volume reduction rate: 77.62%), respectively, which were all significantly decreased from the pre-treatment period (all P<0.05). The VAS scores of pain of the OMA patients at 3, 6 and 12 months of dienogest treatment all were 0 mm. Blood cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19-9) levels decreased progressively during treatment (all P<0.05). There were no statistical differences in the coagulation indexes, liver and kidney function indexes of the patients during dienogest treatment compared with those before treatment (all P>0.05). During the follow-up period, there were a few patients with changes in the growth sites or lesion category of the breast nodules, but there were no occurrence of breast cancer or precancerous lesions. Conclusion: Dienogest is effective in reducing OMA volume and alleviating endometriosis-related pain with few adverse effects.

[Clinical analysis of maternal autoantibody-mediated complete left bundle branch block in 9 children].

Objective: To analyze the clinical characteristics, treatment, and outcomes of children with complete left bundle branch block (CLBBB) mediated by maternal autoantibodies. Methods: A retrospective analysis was conducted on nine children diagnosed with maternal autoantibody-mediated CLBBB, treated at Beijing Anzhen Hospital and Fujian Provincial Hospital from March 2015 to August 2023. Their clinical characteristics, electrocardiographic and echocardiographic findings before and after treatment were reviewed. Paired sample t-test was used for inter-group comparison. Results: Among the mothers, 6 had positive antinuclear antibodies (ANA), 5 had anti-Sjogren syndrome antigen A antibodies, and 3 had anti-Ro-52 antibodies. The cohort included one female and eight male children, diagnosed with CLBBB at the age of 1 (2, 13) months. The positive autoantibodies in the infants, consisted with maternal antibodies, were detected within the first 3 months of life among 3 cases. Treatments included anti-heart failure therapy, myocardial nutritional support, intravenous immunoglobulin (IVIG) and glucocorticoids. Before treatment, the levels of troponin I (0.175 (0.060, 10.270) µg/L) and N-terminal pro-B-type natriuretic peptide (420 (327, 12 865) ng/L) were elevated, which normalized in most cases after treatment. Post-treatment, the QRS duration significantly shortened compared to pre-treatment ((137±15) vs.(169±25) ms, t=3.76, P<0.001), and the QTc interval significantly decreased ((433±41) vs. (514±27) ms, t=4.95, P=0.001). Before treatment, varying degrees of mitral and tricuspid regurgitation and marked interventricular septal dyskinesia were observed in echocardiography. After treatment, valve regurgitation and ventricular septum motion significantly improved, with a marked increase in left ventricular ejection fraction ((51±13)% vs. (27±6)%, t=-6.66, P<0.001). Conclusions: Maternal autoantibody-mediated CLBBB in children presents with chronic heart failure in infancy. Early treatment with anti-heart failure medications, IVIG and glucocorticoids can improve clinical symptoms.

[Current situation of surgical treatment of gallbladder polyps and some problems that should be paid attention to].

Gallbladder polyp is a common disease of gallbladder, the incidence of gallbladder polyp in China is about 5%~10%, and the trend is increasing year by year. The patients with gallbladder polyps had no obvious clinical symptoms, which was more than that found by ultrasonography during physical examination. At present, the diameter of gallbladder polyps>10 mm is still used by clinicians as the main surgical indication for cholecystectomy. According to the data, about 80% to 90% of gallbladder polyps are cholesterol type polyps and benign gallbladder polyps. For these patients whose gallbladder is removed due to benign gallbladder polyps, we consider that we can continue to observe or retain the gallbladder, without having to bear the adverse consequences that may be caused by gallbladder removal. Based on the literature analysis at home and abroad, this paper discusses the surgical treatment of gallbladder polyps and the results of postoperative pathological diagnosis, and reminds the majority of clinicians to be careful when removing gallbladder polyps.

[Analysis of 10 cases of brentuximab vedotin combined with chemotherapy in the treatment of children with refractory and or relapsed classic Hodgkin lymphoma].

Objective: To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin's lymphoma (R/R cHL). Methods: Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment. Conclusion: Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin's lymphoma in children.

[Efficacy of oral testosterone undecanoate in children with androgen insensitivity syndrome].

Objective: To investigate the efficacy and safety of oral testosterone therapy in individuals diagnosed with androgen insensitivity syndrome (AIS). Methods: A self-controlled study design was utilized, focusing on individuals with AIS who were genetically diagnosed at the Department of Endocrinology, Genetics, and Metabolism of Beijing Children's Hospital between 2009 and 2021. These patients underwent treatment involving the administration of testosterone. The primary observed indexes include the measurement of penis length, which should meet the minimal surgical standard (penis length≥2.5 cm) or greater than or equal to -2.5 s (lower limit of normal). Secondary observed indexes include penile length standard deviation score (PL-SDS), an increase in penis longitude (ΔPL), medication dosage, the course of therapy, and safety indicators, among others. There were 4 courses of treatment. After each course, patients were evaluated to determine whether termination of treatment was appropriate. Patients who exhibited inadequate post-treatment penile length growth were advised to continue with further treatment. The statistical methodology included t-test, and a Wilcoxon rank sum test to describe efficacy and safety. The patients were followed up until 2023. Results: The study comprised a total of 51 individuals with AIS, comprising 33 males and 18 females (gender of registered permanent residence). Among these patients, 10 were diagnosed with complete androgen insensitivity syndrome (CAIS) and 41 were diagnosed with partial androgen insensitive syndrome (PAIS). There were 2 children with CAIS were diagnosed by doctors and prescribed testosterone undecanoate, but the children did not really take medicine.The penile length of CAIS patients could not be measured (penile length<0.5 cm) before and after treatment. For PAIS patients, baseline penile length and PL-SDS were (2.3±0.6) cm and -3.7±1.3, respectively. The measurements for penile length and PL-SDS after each treatment course were recorded as follows: (2.7±0.8), (2.8±0.6), (2.6±0.4), (2.6±0.4) cm and -2.8±1.6, 2.5±1.6, 2.9±1.2, -3.2±0.9, respectively. Both penile length and PL-SDS interventions showed statistically significant gains when compared to the baseline performance of the 4 courses (t=4.05、3.56、2.55、2.23 and 3.88、3.50、2.50、2.19, all P<0.05). Before treatment, 13 PAIS patients (32%) reached 2.5 cm and seven (17%) reached greater than or equal to -2.5 s. Following the initial, subsequent, third, and fourth therapeutic interventions, 18 cases (44%), 24 cases (59%), 25 cases (61%), and 26 cases (63%) reached 2.5 cm, respectively. Additionally, A total of 12 cases (29%), 15 cases (37%), 20 cases (49%), and 21 cases (51%), respectively, were found to reach greater than or equal to -2.5 s. The study involved the longitudinal monitoring of patients with the highest recorded age being 13.7 years. The weight, height, body mass index, bone age/age, cholesterol, hemoglobin and so on were all within the normal range and the difference were not statistically significant (all P>0.05). All 49 patients were no abnormalities in blood electrolyte, liver and kidney function and thyroid function and no changes in precocious puberty, pubic hair growth, aggressive behavior, vulvar skin darkening, diarrhea or other conditions. Conclusions: Testosterone undecanote in children with CAIS was no effective. The initial course of treatment for patients with PAIS demonstrates observable enhancements in penile length and PL-SDS. For patients with inadequate penile length growth, continued treatment in subsequent courses (such as the second, third, and fourth courses) is recommended toenhance outcomes gradually. Testosterone undecanoate was safe and effective for the majority of individuals with PAIS patients, with few adverse effects and good treatment tolerance.

[Advances in electrowetting-on-dielectric digital microfluidics technology for disease diagnosis and prevention applications].

Rapid and accurate diagnostic technologies are crucial for early detection and diagnosis of diseases. Electrowetting-on-dielectric digital microfluidics, with its high-precision detection and high-throughput screening capabilities, significantly enhances the accuracy and efficiency in early disease diagnosis and personalized treatment, enabling swift disease detection and widespread screening. This article provides a comprehensive review of the working principles and fabrication processes of digital microfluidic chips based on electrowetting on dielectric method. It details the latest research progress in the areas of nucleic acids, proteins, and cells, organizes the commercialization of digital microfluidics technology, and finally discusses the current challenges and future directions of digital microfluidic chips.

Utilities of environmental radioactivity tracers in assessing sequestration potential of carbon in the coastal wetland ecosystems.

Demand for accurate estimation of coastal blue carbon sequestration rates in a regular interval has recently surged due to the increasing awareness of nature-based climate solutions to alleviate adverse impacts stemming from the recent global warming. The robust estimation method is, however, far from well-established. The international community requires, moreover, to quantify its effect of "management." This article tries to provide the environmental isotope community with basic biophysical features of coastal blue carbon ecosystems to identify a suitable set of environmental isotopes for promoting coastal ocean-based climate solutions. This article reviews (i) the primary biophysical characteristics of coastal blue carbon ecosystems and hydrology, (ii) their consequential impact on the accumulation and preservation of organic carbon (OC) in the sediment column, (iii) suitable environmental isotopes to quantifying the sedimentary organic carbon accumulation, outwelling of the carbon-containing byproducts of decomposition of biogenic organic matter and acid neutralizing alkalinity produced in situ sediment to the offshore. Above-ground biomass is not cumulative over the years except for mangrove forests within coastal blue carbon systems. Non-gaseous carbon sequestration and loss occur mainly as a form of sediment organic carbon (SOC) and dissolved carbon in an intertidal and subtidal bottom sediment body in a slow, patchy, and dispersive way, on which this article focuses. Investigating environmental radionuclides is probably the most cost-effective effort to contribute to defining the offshore spatial extent of coastal blue carbon systems except for seagrass beds (e.g., Ra isotopes), to quantify millimeter per year scale carbon accretion and loss within the systems (e.g., 7Be, 210Pb) and a liter per meter of coastline per a day scale water movement from the systems (Ra isotopes). A millimeter-scale spatial and an annual (or less) time-scale resolution offered by the use of environmental isotopes would equip us with a novel tool to enhance the carbon storage capacity of the coastal blue carbon system.

[The efficacy and safety of immunotherapy combined with chemotherapy neoadjuvant in locally advanced resectable hypopharyngeal squamous cell carcinoma].

Objective: To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients. Methods: This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy. Results: By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence. Conclusions: The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

[Immunogenicity, safety and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years].

Objective: To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years. Methods: An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster. Results: The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A's 44.79 (36.94-54.30) (P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A's 15.71 (13.24-18.63) (P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion: Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

[Study on formulation and revision of standard limit for formaldehyde in the "Standards for indoor air quality（GB/T 18883-2022）" in China].

Formaldehyde, as an important pollutant in indoor air, has always been of great concern. In the newly issued "Standards for indoor air quality (GB/T 18883-2022)", the standard limit of formaldehyde has been restricted to 0.08 mg/m3. In order to better promote the implementation and application of this new standard, this study reviewed and interpreted the relevant technical content for determining the standard limit, including the indoor concentration and human exposure levels of formaldehyde, the health effects of formaldehyde, and the derivation of safety reference values. It also proposed prospect for the future development and revision of quality standards for formaldehyde in indoor air.

[Association between maternal plasma one-carbon biomarkers during pregnancy and fetal growth in twin pregnancies].

Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P<0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight (ß=-47.9, 95%CI:-94.3- -1.6; P=0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR=0.5, 95%CI: 0.3-0.9; P=0.021) and low birth weight infants (OR=0.6, 95%CI: 0.4-0.9; P=0.020). Increased homocysteine level was associated with increased risks of SGA (OR=1.5, 95%CI: 1.0-2.2; P=0.029) and inconsistent growth in twin fetuses (OR=1.9, 95%CI: 1.0-3.7; P=0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P<0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy (ß=-65.9, 95%CI:-110.6- -21.1; P=0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P<0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.

[Influence of pH value on tube formation of human dermal microvascular endothelial cells and its molecular mechanism].

Objective: To explore the influence of pH value on tube formation of human dermal microvascular endothelial cells (HDMECs) and study its molecular mechanism, so as to provide theoretical basis for the study of promoting angiogenesis in the process of wound healing. Methods: The experimental study methods were applied. HDMECs of 4 or 5 passages in the logarithmic growth phase were collected for experiments. Culture mediums with pH values of 6.4, 6.6, 6.8, 7.0, 7.2, 7.4, 7.6, and 7.8 were prepared, and the cells were adaptively cultured (the same culture method below) for 24 h before further experiments being carried out. After another 36 h of culture, the relative fluorescence value of cytoplasmic pH value was measured by flow cytometry, and the correlation analysis between the relative fluorescence value of cytoplasmic pH value and the medium pH value was carried out. After another 1.5, 2.5, 3.5, 4.5, and 5.5 days of culture, the cell proliferation activity was detected with cell counting kit 8. OrisTM cell migration detection kit was used to detect the remaining area of cell migration at 0 (immediately), 24, and 48 h after removing the cell seeding stopper. Three-dimensional stromal gel cell tube formation experiment was carried out to detect the lumen diameter of tube formed by cells after another 48 h of culture. The protein expressions of phosphorylation sites 473 and 308 of protein kinase B (Akt) were detected by Western blotting after another 48 h of culture. The sample number was 3. Data were statistically analyzed with Pearson correlation analysis, one-way analysis of variance, analysis of variance for factorial design, analysis of variance for repeated measurement, and Bonferroni correction. Results: After another 36 h of culture, the relative fluorescence values of cytoplasmic pH value of cells cultured in pH 6.8-7.8 mediums were significantly higher than the level in pH 6.4 medium (P<0.05); compared with those in pH 6.6-7.0 mediums, the relative fluorescence values of cytoplasmic pH value of cells cultured in pH 7.4-7.8 mediums were significantly increased (P<0.05), and the relative fluorescence value of cytoplasmic pH value of cells cultured in pH 6.6 medium was significantly lower than that in pH 7.0 or 7.2 mediun (with P values all <0.05); the relative fluorescence values of cytoplasmic pH value of cells cultured in pH 7.6 and 7.8 mediums were significantly higher than those in pH 7.2 and 7.4 mediums (P<0.05). The relative fluorescence value of cytoplasmic pH value was significantly positively correlated with the medium pH value (r=0.99, P<0.05). The proliferation activity was similar among cells cultured in 8 mediums of different pH values for another 1.5 days (P>0.05). After another 2.5 days of culture, the proliferation activity of cells cultured in pH 6.4-6.8 mediums was significantly decreased compared with that in pH 7.6 medium (P<0.05). After another 3.5 days of culture, the proliferation activity of cells cultured in pH 7.0-7.8 mediums was significantly higher than that in pH 6.4-6.8 mediums (P<0.05); compared with that in pH 7.6 medium, the proliferation activity of cells cultured in pH 7.0-7.4 and 7.8 mediums was significantly decreased (P<0.05). After another 4.5 or 5.5 days of culture, the proliferation activity of cells cultured in pH 6.8-7.8 mediums was significantly higher than that in pH 6.4 medium (P<0.05); compared with that in pH 6.6 and 6.8 mediums, the proliferation activity of cells cultured in pH 7.0-7.8 mediums was significantly increased (P<0.05). After another 4.5 days of culture, the proliferation activity of cells cultured in pH 7.6 medium was significantly higher than that in pH 7.0 medium (P<0.05). After another 5.5 days of culture, the proliferation activity of cells cultured in pH 7.2-7.6 mediums was significantly increased compared with that in pH 7.0 medium (P<0.05); the proliferation activity of cells cultured in pH 7.2 and 7.4 mediums was significantly lower than that in pH 7.6 medium (with P values all <0.05) but significantly higher than that in pH 7.6 medium (with P values all <0.05). Immediately after removing the cell seeding stopper, the remaining migration areas were similar among cells cultured in 8 mediums of different pH values (P>0.05). At 24 h after removing the cell seeding stopper, the remaining migration areas of cells cultured in pH 6.6-7.8 mediums were significantly smaller than the area in pH 6.4 medium (P<0.05); compared with those in pH 6.6 and 6.8 mediums, the remaining migration areas of cells cultured in pH 7.0 to 7.6 mediums were significantly reduced (P<0.05). At 48 h after removing the cell seeding stopper, compared with those in pH 6.4 and 6.6 mediums, the remaining migration areas of cells cultured in pH 7.0-7.8 mediums were significantly reduced (P<0.05); the remaining migration areas of cells cultured in pH 7.2 and 7.4 mediums were significantly smaller than those in pH 6.8, 7.0, and 7.8 mediums (P<0.05) but significantly larger than the area in pH 7.6 medium (P<0.05); the remaining migration area of cells cultured in pH 7.6 medium was significantly smaller than that in pH 6.8 or 7.8 medium (with P values all <0.05). After another 48 h of culture, the lumen diameters of tubes formed by cells cultured in pH 7.0, 7.2, 7.4, 7.6, and 7.8 mediums were (5.0±0.5), (7.6±0.9), (8.5±0.7), (11.0±0.8), and (5.3±0.8) µm, respectively, which were significantly longer than (2.8±0.8) µm in pH 6.4 medium (P<0.05); the lumen diameters of tubes formed by cells cultured in pH 6.6 ((4.2±0.3) µm), 6.8 ((4.5±0.6) µm), 7.0, and 7.8 mediums were significantly shorter than the diameter in pH 7.6 medium (P<0.05). After another 48 h of culture, compared with those in pH 6.4 and 6.6 mediums, the protein expressions of Akt phosphorylation sites 473 and 308 of cells cultured in pH 6.8 to 7.8 mediums were significantly increased (P<0.05). Moreover, the protein expression of Akt phosphorylation site 308 of cells cultured in pH 6.6 medium was significantly higher than that in pH 6.4 medium (P<0.05); compared with the expression in pH 6.8 medium, the protein expressions of Akt phosphorylation site 473 of cells cultured in pH 7.0 and 7.4-7.8 mediums were significantly increased (P<0.05); compared with the expression in pH 7.6 medium, the protein expressions of Akt phosphorylation site 473 of cells cultured in pH 7.0-7.4 and 7.8 mediums were significantly decreased (P<0.05); compared with the expression in pH 7.8 medium, the protein expressions of Akt phosphorylation site 308 of cells cultured in pH 7.0 to 7.6 mediums were significantly increased (P<0.05). Conclusions: pH value can regulate the lumen diameter of HDMEC-formed capillaries, which is closely related to the activation of Akt. 7.2-7.6 is the appropriate pH value for constructing tissue engineered capillaries.