ObjectiveTo develop traditional Chinese medicine （TCM） formulae for the treatment of nonsevere coronavirus disease 2019 （COVID-19） and to explore its anti-inflammatory mechanism. MethodsThe dysregulated signaling pathways were determined in macrophages from bronchoalveolar lavage fluid of COVID-19 patients and in lung epithelial cells infected with SARS-CoV-2 in vitro based on transcriptome analysis. A total of 102 TCM formulae for the clinical treatment of nonsevere COVID-19 were collected through literature. The pathway-reversing rates of these formulae in macrophages and lung epithelial cells were evaluated based on signature signaling pathways， and the basic formula was determined in conjunction with TCM theory. The commonly used Chinese materia medica for nonsevere COVID-19 were summarized from the 102 TCM formulae as abovementioned. And together with the screening results from the Pharmacopoeia of the People's Republic of China， a “Chinese materia medica pool” was esta-blished for the development of TCM formulae for COVID-19. The regulatory effects of each herb on signaling pathways were obtained based on targeted transcriptome analysis. Oriented at reversing dysregulated signaling pathways of COVID-19， the calculation was carried out， and the artificial intelligent methods for compositing formulae， that are exhaustive method and parallel computing， were used to obtain candidate compound formulas. Finally， with reference to professional experience， an innovative formula for the treatment of nonsevere COVID-19 was developed. The ethanol extract of the formula was evaluated for its anti-inflammatory effects by detecting the mRNA expression of interleukin 1b （Il1b）， C-X-C motif chemokine ligand 2 （Cxcl2）， C-X-C motif chemokine ligand 10 （Cxcl10）， C-C motif chemokine ligand 2 （Ccl2）， nitric oxide synthase 2 （Nos2）， and prostaglandin-endoperoxide synthase 2 （Ptgs2） using reverse transcription-quantitative polymerase chain reaction （RT-qPCR） in RAW264.7 cells treated with lipopolysaccharide （LPS）. ResultsIn macrophages and lung epithelial cells， 34 dysregulated signaling pathways associated with COVID-19 were identified respectively. The effects of the 102 formulae for clinical treatment of nonsevere COVID-19 were evaluated based on the dysregulated signaling pathways and targeted transcriptome， and the result showed that Yinqiao Powder and Pingwei Powder （银翘散合平胃散， YQPWP） ranked first， reversing 91.18% of the dysregulated signaling pathways in macrophages and 100% of the dysregulated signaling pathways in lung epithelial cells. Additionally， YQPWP had the function of scattering wind and clearing heat， resolving toxins and removing dampness in accordance with the pathogenesis of wind-heat with dampness in COVID-19. It was selected as the basic formula， and was further modified and optimized to develop an innovative fomula Qiaobang Zhupi Yin （翘蒡术皮饮， QBZPY） based on expert experience and artificial intelligence in composing formulae. QBZPY can reverse all the dysregulated signaling pathways associated with COVID-19 in macrophages and lung epithelial cells， with the reversing rates of 100%. The chief medicinal of QBZPY， including Lianqiao （Fructus Forsythiae）， Xixiancao （Herba Siegesbeckiae） and Niubangzi （Fructus Arctii）， can down-regulate multiple signaling pathways related with virus infection， immune response， and epithelial damage. RT-qPCR results indicated that compared with the model group， the QBZPY group down-regulated the mRNA expression of Il1b， tumor necrosis factor （Tnf）， Cxcl2， Cxcl10， Ccl2， Nos2 and Ptgs2 induced by LPS in RAW264.7 cells （P＜0.05 or P＜0.01）. ConclusionBased on targeted transcriptome analysis， expert experience in TCM and artificial intelligence， QBZPY has been developed for the treatment of nonsevere COVID-19. The ethanol extract of QBZPY has been found to inhibit mRNA expression of several pro-inflammatory genes in a cellular inflammation model.

OBJECTIVE To assess the blending types and workload of pharmacy intravenous admixture services （PIVAS） in China. METHODS By questionnaire survey， the working status of PIVAS in different levels of hospitals nationwide was investigated， involving the types of blending infusion， daily blending volume of hazardous drugs infusion， parenteral nutrition solution， general and antibacterial drug infusion， intravenous bolus drugs， skin test solution and intravenous agents， as well as the daily packing volume. RESULTS A sample of 750 PIVAS in 30 provinces （autonomous regions， municipalities） across China were surveyed by questionnaire， involving 621 tertiary hospitals and 90 secondary hospitals. The main types of liquid preparation were intravenous infusion， followed by parenteral nutrition solution， and chemotherapy pump （including chemotherapy infusion）， accounting for 99.73%， 79.47% and 43.33%， respectively. The daily blending volume of hazardous drugs infusion， parenteral nutrition solution， general and antibacterial drug infusion， intravenous bolus drugs， skin test solution and intravenous agents in PIVAS of tertiary hospitals were 23.00 （9.00， 56.50） sets， 31.00 （13.97， 74.00） bags， 813.00 （375.00， 2 061.75） bags， 426.00 （210.00， 987.00） bags， 30.00 （6.00， 155.00） ampoules， 30.00 （7.13， 136.84） ampoules， 3 200.00 （1 684.50， 5 554.50） ampoules respectively， while the daily packing volume was 218.50 （52.26， 559.00） bags； above indexes of PIVAS in secondary hospital were 4.00（2.00，12.00）sets， 8.90（3.00，23.00）bags， 270.50（108.00， 2 061.75）bags， 157.00（71.00，987.00）bags， 5.85 （3.75，141.00） ampoules， 0 ampoule， 1 349.00（548.10，2 408.00）ampoules， 107.50（33.25，207.00）bags. CONCLUSIONS The scope of blending types of PIVAS has been significantly expanded， and tertiary hospitals are significantly higher than secondary hospitals in the blending and packing volumes of all types of intravenous fluids and drugs dispensed， showing obvious advantages in dealing with complex medications and high-risk treatments.

OBJECTIVE To know about the current status of medical order auditing in pharmacy intravenous admixture service （PIVAS） of medical institutions nationwide， further improve the management of medical orders in PIVAS， and reduce and eliminate the occurrence of intravenous medication administration errors. METHODS Through the questionnaire survey method， to address the problems and current situation of PIVAS medical order auditing in medical institutions nationwide， experts from each province （autonomous region， municipality directly under the central government） in the research group were responsible for organizing the PIVAS directors of relevant medical institutions in their provinces to fill in the questionnaires on medical order audit and inappropriate medical order interventions， and conduct a statistical analysis of the results. RESULTS A total of valid 751 responses were received to the PIVAS questionnaire on the review of medical prescriptions. Our PIVAS medical order audit is mainly carried out by a combination of manual and computer. The median number of medical orders were audited by PIVAS per day were 700.00-771.00； the median number of new medical orders were audited by PIVAS per day were 209.68-215.00； medical order auditing rates were 85.50%-92.44% averagely； the inappropriate doctor’s orders accounted for 1.82%-1.89% averagely； the intervention rates of inappropriate medical orders ranged 74.90%-79.41%， the success rates of intervention were 79.62%-87.28% averagely； the medication refund rates were 2.92%-3.08%. CONCLUSIONS Most of the PIVAS in China’s healthcare institutions use medical order review software to assist in the review of medical orders， and there are cases of individual PIVAS in which medical orders are not reviewed comprehensively and inappropriate orders are not intervened in， and the standards and processes of medical prescription review need to be improved. It is recommended to emphasize the pharmacist’s responsibility system， standardize the use of prescription review software； gradually expand the scope of medical order review， and adopt a multi-departmental collaborative approach so as to increase the success rate of intervention for inappropriate prescriptions and reduce the rate of PIVAS withdrawals.

Objective To explore the effects of prohibitin 2(PHB2)on sensitivity of non-small cell lung cancer cell line A549 to erlotinib(Erl)and its potential mechanisms.Methods RACK1-specific small interfering RNA was transfected in A549 cells for knocking-down of PHB2.The effects of PHB2 inhibition on cell proliferation and apop-tosis induced by Erl were observed.The colocalization of microtuble-associated protein light chain 3 alpha(LC3)and mitochondria was visualized by MitoTracker staining and green fluorescent protein-microtuble-associated protein light chain 3 alpha(GFP-LC3)transfection.Cell proliferation was detected by 5-ethynyl-2′-deoxyuridine(EdU)staining.Cell colony formation was evaluated by colony forming assay.Apoptotic index of A549 cells was evaluated by TUNEL.Western blot was used to measure the expressions of PHB2 and LC3Ⅱ.Mitochondrial transmembrane potential,cytochrome c and respiratory chain complexⅠ/Ⅱ/Ⅴactivity were analyzed by the commercially availa-ble kits.Results Compared with the siPHB2 and siCtrl+Erl group,the EdU-positive A549 cells and the number of cell colonies decreased significantly(P＜0.05),while the TUNEL-positive A549 cells increased significantly(P＜0.05)in the siPHB2+Erl group.In addition,compared with the siPHB2 and siCtrl+Erl group,mitochondrial transmembrane potential and respiratory chain complexⅠ/Ⅱ/Ⅴactivity decreased significantly(all P＜0.05)and the levels of cytochrome c increased in mitochondrial fractions(P＜0.05)and decreased in cytosolic fractions(P＜0.05)in the siPHB2+Erl group.Conclusions PHB2 inhibition significantly improves sensitivity of A549 cells to Erl,which may be explained by inhibition of PHB2-mediated mitochondrial autophagy.

Objective:To investigate the clinical efficacy and safety of deep hyperthermia combined with sintilimab and nab-PC (albumin-bound paclitaxel + carboplatin) regimen in the treatment of advanced squamous non-small cell lung cancer (NSCLC) with driver gene negative and programmed death-1 receptor ligand 1 (PD-L1) expression positive.Methods:A prospective case-control study was performed. A total of 84 advanced squamous NSCLC patients with driver gene negative and PD-L1 expression positive in Hebei Seventh People's Hospital from January 2020 to December 2022 were collected, and all patients were divided into the observation group and the control group according to the random number table method, with 42 cases in each group. The control group was given the treatment of sintilimab combined with nab-PC regimen, and the observation group was given deep hyperthermia on the basis of the control group. After 4 consecutive cycles of treatment, the short-term efficacy of the two groups was compared. The levels of serum tumor markers [carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA), cytokeratin fragment 19 (CYFR21-1)], and the positive expression rates of immunohistochemistry markers [p40, p63, and cytokeratin 5/6 (CK5/6)] before and after treatment were compared between two groups. Functional Assessment of Cancer Therapy-Lung cancer module (FACT-L) scores, the adverse reactions and the long-term survival of the two groups were compared.Results:There were 26 males and 16 females in the observation group, and the age was (59±11) years; there were 22 males and 15 females in the control group, and the age was (58±11) years. The objective remission rate and the disease control rate were 71.43% (30/42), 90.48% (38/42), respectively in the observation group, and 50.00% (21/42), 80.95% (34/42), respectively in the control group; the objective remission rate in the observation group was higher than that in the control group, and the difference was statistically significant ( χ2 = 4.04, P = 0.044); and there was no statistically significant difference in the disease control rate of both groups ( χ2 = 1.56, P = 0.212). The levels of serum CEA, SCCA and CYFRA21-1, and the positive expression rates of p40, p63, and CK5/6 in the two groups after treatment were lower than those before treatment (all P < 0.05); and the scores of physiological status, functional status, additional concern in FACT-L scores and the total score of the scale after treatment were higher than those before treatment (all P < 0.05). There were no statistically significant differences in the incidence of adverse reactions including thrombocytopenia, neutropenia, leukopenia, anemia, fever of the two groups (all P > 0.05). The median progression-free survival (PFS) time was 6.5 months (95% CI: 3.82-12.75), 5.1 months (95% CI: 3.14-12.26),respectively in the observation group and the control group, and the difference in the median PFS time was statistically significantly of both groups ( χ2 = 4.21, P = 0.040). The median overall survival (OS) time was 12.9 months (95% CI: 6.25-15.46), 9.7 months (95% CI: 4.74-13.02), respectively in the observation group and the control group, and the difference in the median OS time was statistically significantly of both groups ( χ2 = 4.43, P = 0.035). Conclusions:Deep hyperthermia combined with sintilimab and nab-PC regimen in the treatment of advanced squamous NSCLC with driver gene negative and PD-L1 expression positive can effectively reduce the serum tumor markers levels and positive expression rate of immunohistochemical markers, improve the quality of life of patients, and increase the short-term and long-term efficacy.

Objective: To investigate the recessive infection rate of healthy children and guardians in different epidemic periods of hand, foot and mouth disease (HFMD) in Qingdao, analyze the risk factors affecting recessive infection, so as to provide the basis for HFMD prevention and control. Methods: In the nonepidemic period of 2022, the random cluster sampling method was used to selected 546 children and guardians from 4 childcare institutions in Laoshan District and Pingdu City. In the epidemic period of 2023, 690 children and guardians were selected from 6 childcare institutions in Shibei District, Laoshan District and Pingdu District. A questionnair survey was conducted in the epidemic period. Logistic regression analysis was used to analyze the factors affecting the recessive infection. Dominance analysis was used to explore the relative importance of the risk factors affecting recessive infection. Results: The results showed that the recessive infection rates of healthy children and guardians in the epidemic period were 18.84% and 13.62%, respectively; the recessive infection rates were 9.09% and 4.44% in the nonepidemic period, respectively. The results of multivariate Logistic analysis showed that rural areas (OR=4.71, 95%CI=2.57-8.61) and recessive infection of guardians (OR=18.62, 95%CI=7.45-46.56) were positively correlated with recessive infection of HFMD in healthy children (P<0.05). Washing hands (OR=0.09, 95%CI=0.04-0.20), using towels alone (OR=0.17, 95%CI=0.07-0.40), and EV71 vaccination (OR=0.42, 95%CI=0.20-0.87) were negatively correlated with recessive infection of HFMD in healthy children (P<0.05). Public toilets (OR=3.02, 95%CI=1.50-6.09) and drying bedding once per quarter (OR=3.89, 95%CI=1.75-8.68) were positively correlated with recessive infection of HFMD in healthy guardians. Housing with good lighting (OR=0.31, 95%CI=0.12-0.79), and tableware disinfection (OR=0.31, 95%CI=0.15-0.65) were negatively correlated with recessive infection of HFMD in healthy guardians (P<0.05). The results showed that recessive infection of guardians was relatively the most important for healthy children (41.51%), and tableware disinfection was relatively the most important for recessive infection of guardians (28.87%). Conclusions The recessive infections of HFMD are common among healthy populations in Qingdao, and the recessive infection rate among children during the epidemic period is relatively higher. Guardians play an important role in the recessive infection of healthy children. Therefore, healthy education should be strengthened for key populations, especially to enhance parents awareness of prevention and control to reduce the occurrence of recessive infections of hand, foot and mouth disease in children and guardians.

Objective To evaluate both the causal relationship between plasma metabolites and the risk of knee osteoarthritis(KOA)and the potential mediating or masking effect of immune cells using Mendelian randomization(MR)systems.Methods The GWAS data on 1400 plasma metabolites,731 immune cell traits and KOA was retrieved from the genome-wide association study(GWAS)database.Two-way MR analysis was used to evaluate the causal relationship between plasma metabolism and KOA.Two-step mediation MR analysis was conducted to evaluate immune cell traits that might have mediating or masking effects.Results After sensitivity analysis and screening,65 plasma metabolites and 35 immune cell traits were found to have causal relationships with KOA(P＜0.05).Mediation analysis found that CD45RA+CD28-CD8br％CD8br had a mediating effect in the causal relationship between three metabolites(2-hydroxyhi-ppurate,X-07765,X-23739)and the risk of KOA.2-hydroxyhippurate(salicylic acid)exerted a masking effect,and the effect ratio was 0.0412.Conclusion A variety of plasma metabolites and immune cell traits are causally related to KOA,which should not be regarded as a simple degenerative joint disease.The protective effect of salicylic acid against KOA may be weakened by its role in inducing the differentiation of Treg cells,which is worthy of more studies.

Multiple myeloma (MM) is a plasma cell neoplasm characterized by numerous chromosomal number and structural abnormalities, which are of great significance for risk stratification and response evaluation of MM patients. Optical genome mapping (OGM) is a novel technology that has the potential to resolve many of the issues and limitations associated with traditional cytogenetic methods. To date, the clinical utility of OGM has been validated in the fields of cancer, reproduction, and embryonic dysplasia, et al. In this study, we compared OGM to traditional techniques for the first time in five newly diagnosed MM patients, and evaluated the potential of OGM for detecting cytogenetic aberrations and its clinical application value in MM.

Objective:This study aims to explore the survival advantages of different maintenance strategies for MCL.Methods:Clinical data of 693 newly diagnosed MCL patients in multi-centers admitted from April 1999 to December 2019 were collected. 309 cases received maintenance treatment. The characteristics of patients in different maintenance treatment groups were summarized and Kaplan-Meier survival and prognosis analysis were conducted.Results:The overall 3-year and 5-year progression-free survival (PFS) rates were (73.5±2.9) % and (53.6±4.3) %, respectively. The 3-year and 5-year overall survival (OS) rates were (94.2±1.5) % and (82.7±3.2) %, respectively. The clinical features of different maintenance treatment groups were generally consistent. The 3-year PFS rates of rituximab maintenance, lenalidomide maintenance, BTK inhibitor maintenance and dual-drug maintenance were (70.4±4.1) %, (69.1±7.6) %, (86.9±5.0) %, and (80.4±5.1) %, respectively. Corresponding 3-year OS rates were (92.9±2.4) %, (97.3±2.7) %, (97.9±2.1) %, and (95.3±2.7) %, respectively. There were no significant difference in different groups ( P=0.632, 0.313). Survival analysis identified the MCL International Prognostic Index (MIPI) high-risk group and achieving complete remission before maintenance treatment as independent risk factors for PFS. The MIPI high-risk group, high-dose cytarabine application, treatment lines, and early disease progression (POD24) emerged as independent risk factors for OS. Conclusion:Comparing the different maintenance strategies of MCL, the result showed that BTK inhibitors (BTKi) maintenance demonstrated preliminary advantages in survival. Meanwhile, high-risk group according to MIPI and incomplete remission before maintenance treatment were significant factors related to disease progression.

Here we summarized novel Chimeric antigen receptor T-cell immunotherapy (CAR-T) based on the immune material aspect. Young healthy donor T cells, stem cell-like memory T cells, human induced pluripotent stem cells and umbilical cord blood T cells are all potential candidates to enhance CAR-T cell therapy depending on their anti-tumor efficacy. Besides, due to less restricted major histocompatibility complex (MHC) mismatch effect, viral specific T cells, γδT cells, invariant natural killer T cells and macrophages also become idealized T cell sources in terms of Universal CAR-T (UCAR-T) cell therapeutics. In addition, studies demonstrated that more balanced CD4 +/CD8 + T cell ratio and eliminating monocytes during leukapheresis have a positive influence on CAR-T cell functioning, whereas T cells with higher exhaustion markers expression hampers anti-tumor ability of CAR-T cells after infusion. To avoid application of such T cells or mitigate the impact using immune checkpoint inhibitors is of great importance.