This paper summarizes Professor WANG Xiuxia's clinical experience in treating hyperprolactinemia using the liver soothing therapy. Professor WANG identifies liver qi stagnation and rebellious chong qi （冲气） as the core pathomechanisms of hyperprolactinemia. Furthermore， liver qi stagnation may transform into fire or lead to pathological changes such as spleen deficiency with phlegm obstruction or kidney deficiency with essence depletion. The treatment strategy centers on soothing the liver， with a modified version of Qinggan Jieyu Decoction （清肝解郁汤） as the base formula. Depending on different syndrome patterns such as liver stagnation transforming into fire， liver stagnation with spleen deficiency， or liver stagnation with kidney deficiency， heat clearing， spleen strengthening， or kidney tonifying herbs are added accordingly. In addition， three paired herb combinations are commonly used for symptom specific treatment， Danggui （Angelica sinensis） with Chuanxiong （Ligusticum chuanxiong）， Zelan （Lycopus lucidus） with Yimucao （Leonurus japonicus） ， and Jiegeng （Platycodon grandiflorus） with Zisu （Perilla frutescens）.

Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC treatment.

Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core virus-like particles(HBc VLPs)therapy using a mouse colon cancer model. Methods Humanized B-hOX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-hOX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors. Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs. Conclusion Combination therapy of anti-hOX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.

OBJECTIVE To study the interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes. METHODS In vitro ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1，8-cineole （0.25， 0.5 μmol/L） on the level of Fe2+ in pancreatic β cells were investigated. The effects of 1，8-cineole （0.5 μmol/L） combined with ferroptosis inducer Erastin （20 μmol/L） and ferroptosis inhibitor Ferrostatin-1 （20 μmol/L） on the protein expressions of glutathione peroxidase-4 （GPX4） and cyclooxygenase-2 （COX2） were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1，8-cineole （50， 200 mg/kg） on the pathological morphology of pancreatic tissue， the content of iron as well as the protein expressions of GPX4 and COX2 were investigated. RESULTS The results of the cell experiment showed that compared with the model group， pretreatment with 1，8-cineole significantly reduced intracellular Fe2+ levels and upregulated GPX4 protein expression， while downregulated COX2 protein expression in pancreatic β cells （P＜0.05）. After combining with Ferrostatin-1， the expression trends of the above two proteins were the same， while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group， after intervention with 1，8-cineole， the structure of the pancreatic islets in mice recovered intact and their morphology improved； the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly （P＜0.05）， while protein expression of GPX4 was increased significantly （P＜0.05）. CONCLUSIONS 1，8-cineole could ameliorate pancreatic β cell injury induced by diabetes， the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.

OBJECTIVE To evaluate the innovation and sustainable development ability of traditional Chinese medicine(TCM) preparation in medical institutions, and to provide reference for the decision-making of administrative departments and the sustainable development of TCM preparation in hospitals. METHODS Based on the information data of 133 medical institutions in Zhejiang Province, analytic hierarchy process was used to construct the evaluation system of innovation and sustainable development ability of TCM preparation of medical institutions, and the prediction model of evaluation system of TCM preparation room/center was built by back propagation neural network. RESULTS The evaluation index system for innovation and sustainable development of TCM preparations in medical institutions included 4 second-level indexes and 19 third-level indexes. Among them, the number of varieties developed, the number of over one million varieties, the number of registered varieties, the way of research and development, and the area of preparation room had higher weight values, which were 0.15758, 0.12928,0.09343, 0.07879 and 0.07458, respectively. The entropy weight method and analytic hierarchy process index weights were used to construct the back propagation neural network. The overall correlation coefficients of the training models of the Levenberg-Marquardt algorithm and the Scaled Conjugate Gradient algorithm were 0.98983 and 0.93480, respectively. CONCLUSION This study establishes a scientific and effective comprehensive evaluation system for the innovation and sustainable development ability of TCM preparations in medical institutions, which can realize the prediction and evaluation of the comprehensive ability of TCM preparations in medical institutions.

Objective:To summarize the best evidence on case management of patients with home enteral nutrition.Methods:Relevant evidence on the case management of home enteral nutrition patients was retrieved by literature search,and the evidence was extracted and summarized for the literature that met the quality requirements.Result:A total of 10 literatures were included,including 1 guideline,3 expert consensus,2 industry standards,1 systematic review and 3 randomized controlled trials.By establishment of archives,policy management,establishment of multidisciplinary teams,overall evaluation of home enteral nutrition,as well as implementation management,a total of 33 home enteral nutrition case management was summarized from 6 aspects including health education and follow-up,etc.Conclusion:All the summarized relevant evidence about case filing and management of home enteral nutrition patients can be applied in clinical practice to promote the standardized management of home enteral nutrition.

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

OBJECTIVE: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. METHODS: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. RESULTS: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change -13.67, 95% CI -22.70 to -4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). CONCLUSION The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694).
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Male ; Middle Aged ; Female ; Lung Neoplasms/pathology* ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Chemotherapy, Adjuvant ; Patient Reported Outcome Measures ; Quality of Life ; Aged ; Postoperative Period ; Prospective Studies

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To explore the application effect of online and offline blended learning combined with Jigsaw teaching in arterial blood specimen collection of undergraduate nursing interns.Methods:A total of 135 undergraduate nursing interns were randomly divided into the experimental group ( n=66) and the control group ( n=69). The experimental group used the blended learning combined with Jigsaw teaching, while the control group adopted the blended learning combined with PBL teaching. The theoretical examination before and after class, the skill assessment after training, the nursing clinical decision-making consciousness scale, and the teaching satisfaction survey were conducted in the two groups. SPSS 28.0 was used for t-test and Chi-square test. Results:After teaching, the total score of courses and the score of theoretical examination and skill assessment of the experimental group were higher than those of the control group, and the differences were statistically significant ( P<0.05). The total score and the multi-dimension scores of the nursing clinical decision-making consciousness scale in the experimental group were higher than those in the control group, and the differences were statistically significant ( P<0.05). The teaching satisfaction of the experimental group was 92.42% (61/66), which was significantly higher than that of the control group [69.57% (48/69)], and the differences were statistically significant ( P<0.05). Conclusion:Blended learning combined with Jigsaw teaching is applied to collect arterial blood specimens for undergraduate nursing interns, which is beneficial to improve the academic performance and clinical decision-making ability of nursing students.