Objective To formulate the drug packaging material method standards in the 2025 edition of the Pharmacopoeia of the People's Republic of China(referred to as the"Chinese Pharmacopoeia"),to develop the method for the determination of extractable tungsten for prefilled syringes,and to interpret the content of the method to provide guidance and help for its subsequent implementation.Methods The formulation process of"Determination of Extractable Tungsten for Prefilled Syringes"was described.Combining the current domestic and foreign relevant standards,the extraction conditions of samples were explored and verified,and the determination methods of inductively coupled plasma optical emission spectrometer(ICP-OES)and inductively coupled plasma mass spectrometer(ICP-MS)were verified.Results A method was established for extracting tungsten from glass prefilled syringes utilizing water and 0.01 mol·L-1 sodium hydroxide solution as extraction media,respectively,at 75 ℃ through ultrasound.The dissolution amount of tungsten was determined by inductively coupled plasma opticalemission spectrometry(ICP-OES)and inductively coupled plasma mass spectrometry(ICP-MS).Among them,the extraction using 0.01 mol·L-1 sodium hydroxide solution as the extraction medium is a stricter and acceptable alternative approach.Conclusion According to the quality control requirements of products,corporations can choose the appropriate extraction medium according to the method in this standard for the determination of tungsten dissolution in the prefilled syringes.

Objective To formulate the drug packaging material method standards in the 2025 edition of the Pharmacopoeia of the People's Republic of China(referred to as the"Chinese Pharmacopoeia"),to develop the method for the determination of extractable tungsten for prefilled syringes,and to interpret the content of the method to provide guidance and help for its subsequent implementation.Methods The formulation process of"Determination of Extractable Tungsten for Prefilled Syringes"was described.Combining the current domestic and foreign relevant standards,the extraction conditions of samples were explored and verified,and the determination methods of inductively coupled plasma optical emission spectrometer(ICP-OES)and inductively coupled plasma mass spectrometer(ICP-MS)were verified.Results A method was established for extracting tungsten from glass prefilled syringes utilizing water and 0.01 mol·L-1 sodium hydroxide solution as extraction media,respectively,at 75 ℃ through ultrasound.The dissolution amount of tungsten was determined by inductively coupled plasma opticalemission spectrometry(ICP-OES)and inductively coupled plasma mass spectrometry(ICP-MS).Among them,the extraction using 0.01 mol·L-1 sodium hydroxide solution as the extraction medium is a stricter and acceptable alternative approach.Conclusion According to the quality control requirements of products,corporations can choose the appropriate extraction medium according to the method in this standard for the determination of tungsten dissolution in the prefilled syringes.

Objective:To summarize the best evidence for the prevention and nursing of peri-implant diseases in patients with dental implants.Methods:Guidelines, systematic reviews, evidence summaries, and expert consensus on prevention and nursing of peri-implant diseases in patients with dental implants were electronically retrieved on Guidelines International Network, Agency for Healthcare Research and Quality, Medlive, UpToDate, BMJ Best Practice, Cochrane Library, Web of Science, PubMed, China Biology Medicine disc, China National Knowledge Infrastructure and so on. The search period was from database establishment to June 1, 2023. Two researchers conducted a quality evaluation and extracted evidence from the included literature.Results:A total of 15 articles were included, including two guidelines, six expert consensus, and seven systematic reviews. Twenty pieces of evidence on the prevention and nursing of peri-implant diseases in patients with dental implants were summarized from five aspects: risk factor assessment, nursing measures, oral hygiene guidance, monitoring and follow-up, and health education.Conclusions:The best evidence for the prevention and nursing of peri-implant diseases in dental implant patients summarized is scientifically sound. Medical and nursing staff can apply evidence based on clinical context and patient wishes.

Biological clock genes are essential for regulating various biological processes such as sleep,endo-crine metabolism,and cell proliferation and differentiation.These genes govern the circadian system with approximately 24-h cycles in all living organisms.Recent studies have focused on uncovering the connection between circadian rhythms and tumors.Although the expression of circadian rhythm genes and their proteins is stable in normal tissue cells,in tumor cells,such as colorectal cancer tissues,the expression of these genes is often abnormally up-regulated or down-regulated,which indicates a strong correlation between the abnormal expression of clock genes and the incidence and progression of cancers.In fact,the disruption of the balance of cellular metabolism,cell cycle,cell proliferation,and apoptosis due to the abnormal expression and mutation of biological clock genes can trigger the development of colorectal cancer.In addi-tion,the disrupted circadian rhythm induced by abnormal tumor cell growth can further the advancement of disease,inva-sion,and even metastasis.Our review summarizes the functions and mechanisms of prominent clock genes in the initiation and progression of colorectal cancer based on the recent studies to provide a foundation for the development of personalized chronotherapy regimes encompassing the body's innate biorhythms in standard clinical cancer treatment procedures so as to,ultimately,optimize treatment efficacy and extend patient's life expectancy.

Objective:To systematically evaluate the efficacy and safety of reslizumab targeting interleukin 5 in adjuvant therapy for patients with refractory asthma.Methods:The PubMed, Embase, Cochrane Library, Clinicaltrials.gov, CNKI, VIP, and Wanfang databases were searched (up to June 2022). Randomized controlled trials (RCTs) of reslizumab in adjuvant therapy of refractory asthma were collected. On the basis of conventional treatment for asthma, patients in the trial group was given additional reslizumab while the control group was given placebo. Primary outcome measures included the acute asthma attacks incidence, the changes of forced expiratory volume in the first second (FEV 1), asthma control questionnaire (ACQ) score, asthma quality of life questionnaire (AQLQ) score, and blood eosinophil count before and after adjuvant therapy, and incidence of adverse events. RevMan 5.3 software was used for meta-analysis. The effect sizes of counting data were odds ratio ( OR) and its 95% confidence interval ( CI), while the effect sizes of measurement data were mean difference ( MD) and its 95 %CI. Results:A total of 7 RCTs and 2 506 patients were entered in the analysis, including 1 456 in the trial group and 1 050 in the control group. The meta-analysis showed that, compared to the control group, the acute asthma attacks incidence was lower in patients of the trial group during adjuvant therapy[18.1%(263/1 456) vs. 31.3%(329/1 050), OR=0.50, 95 %CI: 0.41-0.62, P<0.001]; FEV1 and AQLQ score after treatment were higher ( MD=0.13 L, 95 %CI: 0.08-0.17 L, P<0.001; MD=0.18, 95 %CI: 0.04-0.33, P=0.01); the ACQ score and blood eosinophil count were higher ( MD=-0.19, 95 %CI: -0.28--0.10, P<0.001; MD=-0.45×10 9/L, 95 %CI:-0.48×10 9/L--0.42×10 9/L, P<0.001). There were no statistically significant difference in the incidences of overall adverse events, serious adverse events, allergic reactions, and pneumonia compared to those in the control group [63.7% (928/1 456) vs. 71.4% (750/1 050), OR=0.76, 95 %CI: 0.55-1.06, P=0.10; 6.4% (93/1 456) vs. 8.2% (86/1 050), OR=0.91, 95 %CI: 0.66-1.24, P=0.55; 0.4% (5/1 403) vs. 0.1% (1/997), OR=1.66, 95 %CI: 0.41-6.65, P=0.47; 0.6% (9/1 456) vs. 1.0% (10/1 050), OR=0.81, 95 %CI: 0.35-1.87, P=0.63]. Conclusion:Reslizuma has a good efficacy and safety profile in adjuvant treatment for patients with refractory asthma.

Objective:To systematically evaluate the efficacy and safety of reslizumab targeting interleukin 5 in adjuvant therapy for patients with refractory asthma.Methods:The PubMed, Embase, Cochrane Library, Clinicaltrials.gov, CNKI, VIP, and Wanfang databases were searched (up to June 2022). Randomized controlled trials (RCTs) of reslizumab in adjuvant therapy of refractory asthma were collected. On the basis of conventional treatment for asthma, patients in the trial group was given additional reslizumab while the control group was given placebo. Primary outcome measures included the acute asthma attacks incidence, the changes of forced expiratory volume in the first second (FEV 1), asthma control questionnaire (ACQ) score, asthma quality of life questionnaire (AQLQ) score, and blood eosinophil count before and after adjuvant therapy, and incidence of adverse events. RevMan 5.3 software was used for meta-analysis. The effect sizes of counting data were odds ratio ( OR) and its 95% confidence interval ( CI), while the effect sizes of measurement data were mean difference ( MD) and its 95 %CI. Results:A total of 7 RCTs and 2 506 patients were entered in the analysis, including 1 456 in the trial group and 1 050 in the control group. The meta-analysis showed that, compared to the control group, the acute asthma attacks incidence was lower in patients of the trial group during adjuvant therapy[18.1%(263/1 456) vs. 31.3%(329/1 050), OR=0.50, 95 %CI: 0.41-0.62, P<0.001]; FEV1 and AQLQ score after treatment were higher ( MD=0.13 L, 95 %CI: 0.08-0.17 L, P<0.001; MD=0.18, 95 %CI: 0.04-0.33, P=0.01); the ACQ score and blood eosinophil count were higher ( MD=-0.19, 95 %CI: -0.28--0.10, P<0.001; MD=-0.45×10 9/L, 95 %CI:-0.48×10 9/L--0.42×10 9/L, P<0.001). There were no statistically significant difference in the incidences of overall adverse events, serious adverse events, allergic reactions, and pneumonia compared to those in the control group [63.7% (928/1 456) vs. 71.4% (750/1 050), OR=0.76, 95 %CI: 0.55-1.06, P=0.10; 6.4% (93/1 456) vs. 8.2% (86/1 050), OR=0.91, 95 %CI: 0.66-1.24, P=0.55; 0.4% (5/1 403) vs. 0.1% (1/997), OR=1.66, 95 %CI: 0.41-6.65, P=0.47; 0.6% (9/1 456) vs. 1.0% (10/1 050), OR=0.81, 95 %CI: 0.35-1.87, P=0.63]. Conclusion:Reslizuma has a good efficacy and safety profile in adjuvant treatment for patients with refractory asthma.

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68⁺ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

Objective:To explore the effect of hydrogen sulfide (H 2S) on modulating the subunit Kir6.2 of adenosine triphosphate sensitive potassium channels via the cyclic guanosine monophosphate-dependent protein kinase (cGMP/PKG) signaling pathway in epileptic rat models. Methods:Sixty adult male SD rats were randomly divided into the following six groups (10 rats in each group) by random number table method: control, epileptic, H 2S donor, H 2S donor+epileptic, KT5823 (one inhibitor of the cyclic guanosine monophosphate-dependent protein kinase)+H 2S donor+epileptic, and glibenclamide (one inhibitor of the adenosine triphosphate sensitive potassium channels)+H 2S donor+epileptic groups. Except the control group, SD rats were intraperitoneally injected with plentylenetetrazole to make the kindling models and their behaviours were recorded including the latency period, the grade, and the duration of the first epileptic seizure according to the Racine′s standard. The waveforms of electroencephalogram (EEG) in hippocampus were also recorded during the seizure. The mRNA and protein levels of PKG and Kir6.2 in hippocampus were evaluated by Western blotting and quantitative real-time polymerase chain reaction, and the hippocampal concentrations of cGMP and phosphorylation of cyclic guanosine monophosphate-dependent protein kinase (p-PKG) were detected by enzyme linked immunosorbent assay. Results:Rats in the epileptic group showed Ⅳ-Ⅴ grade of epileptic seizure [4.500 (4.000, 4.875)], short latency period [(10.37±8.21) min] but long duration [(69.50±24.37) s] of seizure. Compared to the epileptic group, rats in the H 2S donor group showed Ⅱ-Ⅲ grade of epileptic seizure ( P=0.004), significantly longer latency period ( P<0.001), and shorter duration of seizure ( P<0.001). Compared to the H 2S donor+epileptic group, rats in the KT5823+H 2S donor+epileptic group showed Ⅲ-Ⅳ grade of epileptic seizures, significantly shorter latency period ( P<0.001), and longer duration of seizure ( P<0.001). The results of EEG showed that the wave patterns in the epileptic group were spike or sharp waves and the amplitudes were largest [(190.570±23.590) μV]. Compared with the epileptic group, amplitudes were reduced ( P<0.001) in the H 2S donor+epileptic group. PKG mRNA and PKG protein were expressed differently among all groups (PKG mRNA: n=5, H=26.714, P<0.001; PKG protein: n=5, F=30.597, P<0.001). Compared with the control group, the expression of both PKG mRNA and PKG protein was decreased (PKG mRNA: 1.000±0.001 vs 0.782±0.064, P=0.023; PKG protein: 0.550±0.037 vs 0.145±0.020, P=0.042) in the epileptic group. Besides, Kir6.2 mRNA and Kir6.2 protein were expressed differently among all groups (Kir6.2 mRNA: n=5, H=27.761, P<0.001; Kir6.2 protein: n=5, F=60.659, P<0.001). Compared with the control group, the expression of both Kir6.2 mRNA and Kir6.2 protein was decreased (Kir6.2 mRNA: 1.000±0.001 vs 0.897±0.033, P=0.004; Kir6.2 protein: 0.384±0.035 vs 0.215±0.016, P=0.024) in the epileptic group. And the concentrations of cGMP and p-PKG were decreased (cGMP: P<0.001; p-PKG: P<0.001) in the epileptic group. The results in the H 2S donor+epileptic group were up-regulated (PKG mRNA: P=0.047; PKG protein: P<0.001; Kir6.2 mRNA: P=0.011; Kir6.2 protein: P<0.001; cGMP: P<0.001; p-PKG: P<0.001) compared with the epileptic group. However, the results in the KT5823+H 2S donor+epileptic group were down-regulated (PKG mRNA: P=0.015; PKG protein: P=0.027; Kir6.2 mRNA: P=0.013; Kir6.2 protein: P=0.017; cGMP: P=0.005; p-PKG: P<0.001) compared with the H 2S donor+epileptic group. Conclusion:A possible mechanism is that H 2S prevents the epileptic seizure from modulating the subunit Kir6.2 of ATP sensitive potassium channels via the cGMP/PKG signaling pathway.

Objective To investigate the comprehensive effect and impact path of family environment,rearing style and personality on adolescents with mental disorder.Methods A sample of 200 adolescents with mental disorders and 228 normal adolescents were tested with Family Environment Scale (FESCV),Family Upbringing Style Questionnaire (FUSO),Big Five Personality Questionnaire (NEO-FFI-R) and Psychological Symptom Inventory-100(PSI-I00).Regression analysis and path analysis were used to explore influence and path of rearing style,family environment and personality on mental health.Results The total score PSI-100 in case group (204.0±68.6) was higher than that in control group (146.9±38.4)(t=10.43,P＜0.01).Regression analysis revealed that mental health was affected by rearing style (R2 =0.208) such as mother supervision-control (β =-0.249),father understands-blame (β =-0.195),mother warmth-wildness (β=-0.228) and mother acceptance-rejection (β=0.201),family environment (R2 =0.244) such as conflict (β=0.309),organization (β=-0.196) and expressiveness (β=-0.141),and personality traits (R2 =0.452)such as neuroticism (β=0.412),agreeableness (β=-0.237) and conscientiousness (β=-0.203).Path Analysis showed that personality traits directly affected mental health (β=-0.90),parenting style indirectly influenced mental health (β=0.51) by personality,the family environment had direct (β=0.20) and indirect (β=0.72) effects on mental health,and the model fits well (x2/df =2.160,RMSEA =0.052,GFI =0.88,AGFI =0.84,PGFI =0.67,NFI =0.91,RFI =0.89,IFI =0.95,TLI =0.94,CFI =0.95),and three factors explained 61％ of variation on symptom total score.Conclusion The family environment,family upbringing style and personality traits have significant effect on the adolescent's mental disorder.The personality traits are the most important variables affecting mental health family upbringing style affect mental health indirectly through personality traits,and family environment directly and indirectly affected on the mental health.

Objective To explore family environment,parenting style,and personality of the patients with internalizing and externalizing mental disorders.Methods 137 adolescents with internalizing mental disorder(IMD),63 adolescents with externalizing mental disorder(EMD) and 228 normal subjects (control group) were investigated with Family Environment Scale-Chinese Version (FES-CV),Family Upbringing Style Questionnaire (FUSQ) and the NEO Five Factor Inventory (NEO-FFI).Results (1) The IMD group scored significantly lower on the cohesion (6.17 ± 2.68),active recreational orientation (3.84 ±2.50),moral-religious emphasis (4.48± 1.65),organization (5.35±2.30),expressiveness (4.60±2.00),achievement orientation (5.31 ± 1.84),and higher on the conflict (4.01 ± 2.38) than control group (P＜ 0.05).The EMD group scored only higher on the conflict (4.01±2.38) than control group (P＜0.05).(2) The all dimensional scores(apart from the parent's expect-demanding) of the IMD group were significantly lower than that of control group on the FUSQ (P＜0.05).The scores on the mother's democracy-authoritarian,parent care-protect,catholic-indulgences,parental-control,and expect-demanding were significantly lower in the EMD group than those in the control group (P＜0.05).(3) Relative to the control group,the IMD group got lower scores on the agreeableness (42.02±5.01),conscientiousness (38.91±8.01),and extraversion (35.17±8.57),and higher score on the neuroticism (40.10±8.55);the EMD group got lower scores on the agreeableness(42.75±5.12),conscientiousness (39.95±8.27) and openness (40.00±6.75).Conclusion Adolescents with mental disorders are living in conflict and discord family environment,feel more negative parenting such as authoritarian,harsh,indulgence,control,and demanding,and show some unhealthy personality such as low agreeableness,low conscientiousness,and high neurotic.