This paper summarizes professor WANG Qingguo's experience in treatment of headache based on the "achieving harmony by unblocking and balancing" concept. It is considered that although the pathogenesis of headache is generally attributed to "pain arises from obstruction" and "pain arises from malnourishment"， clinical presentations often involve a complex mixture of deficiency and excess， as well as cold and heat patterns. Professor WANG proposes the diagnostic and therapeutic theory of "achieving harmony by unblocking and balancing"， advocating for equal emphasis on "freeing the flow of qi and blood" and "regulating the balance of yin and yang". He has summarized eight treatment methods for common headache patterns. For wind-cold attacking the collaterals， treatment should focus on dispersing and unblocking through modified Gegen Decoction （葛根汤）. For wind-dampness binding， it is recommended to unblock and drain， using modified Qingshang Juantong Decoction （清上蠲痛汤）. For damp-heat congestion， unblocking and clearing is the method， using modified Toufeng Shen Formula （头风神方）. For liver-gallbladder qi constraint， unblocking and soothing is the treatment principle， and modified Sanpian Decoction （散偏汤） is suggested. For insufficiency of center qi， even supplementation method is recommended， and modified Yiqi Congming Decoction （益气聪明汤） can be used. For liver yang hyperactivity， unblocking and subduing are combined， using modified Xunlong Decoction （驯龙汤）. For deficiency-cold in the liver and stomach， warming， harmonizing， unblocking， and descending are applied， using modified Wuzhuyu Decoction （吴茱萸汤）. For blood deficiency with cold congelation， unblocking and nourishing are undertaken together， using modified Danggui Sini Decoction （当归四逆汤）. The ultimate goal is to restore the dynamic balance of yin， yang， qi， and blood in the body， thereby allevia-ting pain by restoring clarity and function to the head orifices.

This paper summarizes professor WANG Qingguo's experience in treatment of headache based on the "achieving harmony by unblocking and balancing" concept. It is considered that although the pathogenesis of headache is generally attributed to "pain arises from obstruction" and "pain arises from malnourishment"， clinical presentations often involve a complex mixture of deficiency and excess， as well as cold and heat patterns. Professor WANG proposes the diagnostic and therapeutic theory of "achieving harmony by unblocking and balancing"， advocating for equal emphasis on "freeing the flow of qi and blood" and "regulating the balance of yin and yang". He has summarized eight treatment methods for common headache patterns. For wind-cold attacking the collaterals， treatment should focus on dispersing and unblocking through modified Gegen Decoction （葛根汤）. For wind-dampness binding， it is recommended to unblock and drain， using modified Qingshang Juantong Decoction （清上蠲痛汤）. For damp-heat congestion， unblocking and clearing is the method， using modified Toufeng Shen Formula （头风神方）. For liver-gallbladder qi constraint， unblocking and soothing is the treatment principle， and modified Sanpian Decoction （散偏汤） is suggested. For insufficiency of center qi， even supplementation method is recommended， and modified Yiqi Congming Decoction （益气聪明汤） can be used. For liver yang hyperactivity， unblocking and subduing are combined， using modified Xunlong Decoction （驯龙汤）. For deficiency-cold in the liver and stomach， warming， harmonizing， unblocking， and descending are applied， using modified Wuzhuyu Decoction （吴茱萸汤）. For blood deficiency with cold congelation， unblocking and nourishing are undertaken together， using modified Danggui Sini Decoction （当归四逆汤）. The ultimate goal is to restore the dynamic balance of yin， yang， qi， and blood in the body， thereby allevia-ting pain by restoring clarity and function to the head orifices.

Objective:To investigate effects of picroside Ⅱ(PⅡ)on proliferation,apoptosis and immune escape of lung cancer cells by regulating C-C motif chemokine ligand 2(CCL2)/C-C motif chemokine receptor 2(CCR2)signaling axis.Methods:Human lung cancer cells NCI-H292 were cultured and treated with 0,5,10,20,40 and 80 μmol/L PⅡ,MTT method was applied to detect cell viability.Experiment was separated into control group,low,medium and high concentrations PⅡ groups(PⅡ-L,PⅡ-M,PⅡ-H,10,20 and 40 μmol/L PⅡ),high concentration PⅡ+CCL2 overexpression negative control group(PⅡ-H+pcDNA-NC,40 μmol/L PⅡ+pcDNA-NC)and high concentration PⅡ+CCL2 overexpression group(PⅡ-H+CCL2,40 μmol/L PⅡ+pcDNA-CCL2).EdU method was applied to measure cell proliferation;flow cytometry was applied to measure cell apoptosis;immunoblotting was applied to determine expressions of CCL2,CCR2,B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax).Lung can-cer cells in each group were co-cultured with CD8+T cells,Trypan blue staining was applied to measure CD8+T cell viability;ELISA was applied to determine levels of programmed death receptor-ligand 1(PD-L1),IL-10,IFN-γ and TGF-β.Results:Compared with 0 μmol/L,cell viability treated with 10,20,40 and 80 μmol/L PⅡ were significantly reduced(P<0.05),and 10,20 and 40 μmol/L PⅡ were selected for subsequent experiments.Compared with control group,positive rate of EdU and expressions of Bcl-2,CCL2 and CCR2 in PⅡ-L group,PⅡ-M group and PⅡ-H group were decreased sequentially(P<0.05),while apoptosis rate and expression of Bax were increased sequentially(P<0.05).Compared with PⅡ-H+pcDNA-NC group,positive rate of EdU and expressions of Bcl-2,CCL2 and CCR2 in PⅡ-H+CCL2 group were increased obviously(P<0.05),while apoptosis rate and expression of Bax were de-creased significantly(P<0.05).After co-culturing with CD8+T cells,compared with control group,levels of IL-10,TGF-β and PD-L1 in PⅡ-L group,PⅡ-M group and PⅡ-H group were decreased sequentially(P<0.05),while CD8+T cell viability and level of IFN-γ were increased sequentially(P<0.05).Compared with PⅡ-H+pcDNA-NC group,levels of IL-10,TGF-β and PD-L1 in PⅡ-H+CCL2 group were increased obviously(P<0.05),while CD8+T cell viability and level of IFN-γ were reduced significantly(P<0.05).Conclu-sion:PⅡ may inhibit proliferation and immune escape of lung cancer cells,and promote cell apoptosis by inhibiting CCL2-CCR2 sig-naling axis.

Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the effects of asiaticoside(AS)on epithelial-mesenchymal transition(EMT)and radiotherapy sensitivity of esophageal cancer(EC)cells by its mechanism of regulating the hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods EC9706 cells were subjected to different concentrations of AS or different doses of radiation.Methyl thiazolyl tetrazolium method was used to detect cell proliferation and calculate the half-maximal inhibitory con-centration.EC9706 cells were divided into a control group,radiology group(X-ray irradiation),AS group,combined group(AS+X-ray irradiation),and activator group(AS+X-ray irradiation+HIF-1α/VEGF pathway activator dimethyloxallyl glycine).Plate cloning experi-ments were conducted to detect sensitivity,and Transwell assays were used to detect cell migration and invasion.Flow cytometry helped detect apoptosis,and real-time quantitative polymerase chain reaction detected the expression of HIF-1α and VEGF mRNA.Western blotting method was used to detect the expression of matrix metalloproteinase-2(MMP-2),vimentin,E-cadherin,Bcl-2 associated X protein(Bax),HIF-1α,and VEGF proteins.Results With the increase of AS concentration and radiation dose,the cell viability of EC9706 cells gradually decreased;compared with the control group,the survival fraction;the numbers of cells that had migrated and invaded;the expression of HIF-1α and VEGF mRNA;and the expression of MMP-2,vimentin,HIF-1α,and VEGF in the radiology group and AS group were reduced;further,the apoptosis rate and the expression of E-cadherin and Bax were increased(P＜0.05).Compared with the radiology group and AS group,the survival fraction;the numbers of cells that had migrated and invaded;the expression of HIF-1αand VEGF mRNA;and the expressions of MMP-2,vimentin,HIF-1α,and VEGF in the combined group were reduced;the apoptosis rate and the expression of E-cadherin and Bax were increased(P＜0.05).In comparison with the combined group,the changes in the above indicators in the activator group were reversed(P＜0.05).Conclusion AS may inhibit EMT by inhibiting the HIF-1α/VEGF signaling pathway,thus enhancing the radiotherapy sensitivity of EC cells.

Objective:To explore the potential causal relationships between major depressive disorder(MDD),anxiety disorder(AD)and various highly prevalent cancers from the genetic perspective.Methods:Sum-mary statistics from large-scale genome-wide association studies(GW AS)were analyzed using a bidirectional two-sample Mendelian randomization(MR)approach.The inverse variance weighting method(IVW)was usedas the main analytical approach.The intercept term of MR-Egger regression and the MR-PRESSO method were adopted for the pleiotropy test.Results:The IVW analysis revealed potential causal relationships between MDD and breast cancer[OR(95％CI):1.11(1.01-1.22),P＜0.05],AD and lung cancer[OR(95％CI):1.30(1.02-1.65),P＜0.05],and between colon cancer and MDD[OR(95％CI):1.05(1.00-1.11),P＜0.05].The results of the pleiotropy test showed that the intercept terms of the MR-Egger regression were not statistically significant,indica-ting the absence of pleiotropy.The MR-PRESSO method detected outliers only in the relationship between MDD and breast cancer.The association between MDD and breast cancer remained significant after correction for outliers[OR(95％CI):1.10(1.03-1.17),P＜0.05].Conclusion:The study suggests that MDD may be a risk factor for breast cancer,AD may increase the risk factor for lung cancer,and colon cancer may elevate the risk factor of MDD.Moreover,the possibility of reverse causal relationships has been excluded in all these cases.

Objective:To explore the potential causal relationships between major depressive disorder(MDD),anxiety disorder(AD)and various highly prevalent cancers from the genetic perspective.Methods:Sum-mary statistics from large-scale genome-wide association studies(GW AS)were analyzed using a bidirectional two-sample Mendelian randomization(MR)approach.The inverse variance weighting method(IVW)was usedas the main analytical approach.The intercept term of MR-Egger regression and the MR-PRESSO method were adopted for the pleiotropy test.Results:The IVW analysis revealed potential causal relationships between MDD and breast cancer[OR(95％CI):1.11(1.01-1.22),P＜0.05],AD and lung cancer[OR(95％CI):1.30(1.02-1.65),P＜0.05],and between colon cancer and MDD[OR(95％CI):1.05(1.00-1.11),P＜0.05].The results of the pleiotropy test showed that the intercept terms of the MR-Egger regression were not statistically significant,indica-ting the absence of pleiotropy.The MR-PRESSO method detected outliers only in the relationship between MDD and breast cancer.The association between MDD and breast cancer remained significant after correction for outliers[OR(95％CI):1.10(1.03-1.17),P＜0.05].Conclusion:The study suggests that MDD may be a risk factor for breast cancer,AD may increase the risk factor for lung cancer,and colon cancer may elevate the risk factor of MDD.Moreover,the possibility of reverse causal relationships has been excluded in all these cases.

Objective:To investigate effects of picroside Ⅱ(PⅡ)on proliferation,apoptosis and immune escape of lung cancer cells by regulating C-C motif chemokine ligand 2(CCL2)/C-C motif chemokine receptor 2(CCR2)signaling axis.Methods:Human lung cancer cells NCI-H292 were cultured and treated with 0,5,10,20,40 and 80 μmol/L PⅡ,MTT method was applied to detect cell viability.Experiment was separated into control group,low,medium and high concentrations PⅡ groups(PⅡ-L,PⅡ-M,PⅡ-H,10,20 and 40 μmol/L PⅡ),high concentration PⅡ+CCL2 overexpression negative control group(PⅡ-H+pcDNA-NC,40 μmol/L PⅡ+pcDNA-NC)and high concentration PⅡ+CCL2 overexpression group(PⅡ-H+CCL2,40 μmol/L PⅡ+pcDNA-CCL2).EdU method was applied to measure cell proliferation;flow cytometry was applied to measure cell apoptosis;immunoblotting was applied to determine expressions of CCL2,CCR2,B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax).Lung can-cer cells in each group were co-cultured with CD8+T cells,Trypan blue staining was applied to measure CD8+T cell viability;ELISA was applied to determine levels of programmed death receptor-ligand 1(PD-L1),IL-10,IFN-γ and TGF-β.Results:Compared with 0 μmol/L,cell viability treated with 10,20,40 and 80 μmol/L PⅡ were significantly reduced(P<0.05),and 10,20 and 40 μmol/L PⅡ were selected for subsequent experiments.Compared with control group,positive rate of EdU and expressions of Bcl-2,CCL2 and CCR2 in PⅡ-L group,PⅡ-M group and PⅡ-H group were decreased sequentially(P<0.05),while apoptosis rate and expression of Bax were increased sequentially(P<0.05).Compared with PⅡ-H+pcDNA-NC group,positive rate of EdU and expressions of Bcl-2,CCL2 and CCR2 in PⅡ-H+CCL2 group were increased obviously(P<0.05),while apoptosis rate and expression of Bax were de-creased significantly(P<0.05).After co-culturing with CD8+T cells,compared with control group,levels of IL-10,TGF-β and PD-L1 in PⅡ-L group,PⅡ-M group and PⅡ-H group were decreased sequentially(P<0.05),while CD8+T cell viability and level of IFN-γ were increased sequentially(P<0.05).Compared with PⅡ-H+pcDNA-NC group,levels of IL-10,TGF-β and PD-L1 in PⅡ-H+CCL2 group were increased obviously(P<0.05),while CD8+T cell viability and level of IFN-γ were reduced significantly(P<0.05).Conclu-sion:PⅡ may inhibit proliferation and immune escape of lung cancer cells,and promote cell apoptosis by inhibiting CCL2-CCR2 sig-naling axis.

Objective To investigate the effects of asiaticoside(AS)on epithelial-mesenchymal transition(EMT)and radiotherapy sensitivity of esophageal cancer(EC)cells by its mechanism of regulating the hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods EC9706 cells were subjected to different concentrations of AS or different doses of radiation.Methyl thiazolyl tetrazolium method was used to detect cell proliferation and calculate the half-maximal inhibitory con-centration.EC9706 cells were divided into a control group,radiology group(X-ray irradiation),AS group,combined group(AS+X-ray irradiation),and activator group(AS+X-ray irradiation+HIF-1α/VEGF pathway activator dimethyloxallyl glycine).Plate cloning experi-ments were conducted to detect sensitivity,and Transwell assays were used to detect cell migration and invasion.Flow cytometry helped detect apoptosis,and real-time quantitative polymerase chain reaction detected the expression of HIF-1α and VEGF mRNA.Western blotting method was used to detect the expression of matrix metalloproteinase-2(MMP-2),vimentin,E-cadherin,Bcl-2 associated X protein(Bax),HIF-1α,and VEGF proteins.Results With the increase of AS concentration and radiation dose,the cell viability of EC9706 cells gradually decreased;compared with the control group,the survival fraction;the numbers of cells that had migrated and invaded;the expression of HIF-1α and VEGF mRNA;and the expression of MMP-2,vimentin,HIF-1α,and VEGF in the radiology group and AS group were reduced;further,the apoptosis rate and the expression of E-cadherin and Bax were increased(P＜0.05).Compared with the radiology group and AS group,the survival fraction;the numbers of cells that had migrated and invaded;the expression of HIF-1αand VEGF mRNA;and the expressions of MMP-2,vimentin,HIF-1α,and VEGF in the combined group were reduced;the apoptosis rate and the expression of E-cadherin and Bax were increased(P＜0.05).In comparison with the combined group,the changes in the above indicators in the activator group were reversed(P＜0.05).Conclusion AS may inhibit EMT by inhibiting the HIF-1α/VEGF signaling pathway,thus enhancing the radiotherapy sensitivity of EC cells.