The classic formula Fangji Fulingtang is from ZHANG Zhongjing's Synopsis of the Golden Chamber in the Eastern Han dynasty. It is composed of Stephaniae Tetrandrae Radix， Astragali Radix， Cinnamomi Ramulus， Poria， and Glycyrrhizae Radix et Rhizoma， with the effects of reinforcing Qi and invigorating spleen， warming Yang and promoting urination. By a review of ancient medical books， this paper summarizes the composition， original plants， processing， dosage， decocting methods， indications and other key information of Fangji Fulingtang， aiming to provide a literature basis for the research， development， and clinical application of preparations based on this formula. Synonyms of Fangji Fulingtang exist in ancient medical books， while the formula composition in the Synopsis of the Golden Chamber is more widespread and far-reaching. In this formula， Stephaniae Tetrandrae Radix， Astragali Radix， Cinnamomi Ramulus， Poria， and Glycyrrhizae Radix et Rhizoma are the dried root of Stephania tetrandra， the dried root of Astragalus embranaceus var. mongholicus， the dried shoot of Cinnamomum cassia， the dried sclerotium of Poria cocos， and the dried root and rhizome of Glycyrrhiza uralensis， respectively. Fangji Fulingtang is mainly produced into powder， with the dosage and decocting method used in the past dynasties basically following the original formula. Each bag is composed of Stephaniae Tetrandrae Radix 13.80 g， Astragali Radix 13.80 g， Cinnamomi Ramulus 13.80 g， Poria 27.60 g， and Glycyrrhizae Radix et Rhizoma 9.20 g. The raw materials are purified， decocted in water from 1 200 mL to 400 mL， and the decoction should be taken warm， 3 times a day. Fangji Fulingtang was originally designed for treating skin edema， and then it was used to treat impediment in the Qing dynasty. In modern times， it is mostly used to treat musculoskeletal and connective tissue diseases and circulatory system diseases， demonstrating definite effects on various types of edema and heart failure. This paper clarifies the inheritance of Fangji Fulingtang and reveals its key information （attached to the end of this paper）， aiming to provide a theoretical basis for the development of preparations based on this formula.

The classic formula Fangji Fulingtang is from ZHANG Zhongjing's Synopsis of the Golden Chamber in the Eastern Han dynasty. It is composed of Stephaniae Tetrandrae Radix， Astragali Radix， Cinnamomi Ramulus， Poria， and Glycyrrhizae Radix et Rhizoma， with the effects of reinforcing Qi and invigorating spleen， warming Yang and promoting urination. By a review of ancient medical books， this paper summarizes the composition， original plants， processing， dosage， decocting methods， indications and other key information of Fangji Fulingtang， aiming to provide a literature basis for the research， development， and clinical application of preparations based on this formula. Synonyms of Fangji Fulingtang exist in ancient medical books， while the formula composition in the Synopsis of the Golden Chamber is more widespread and far-reaching. In this formula， Stephaniae Tetrandrae Radix， Astragali Radix， Cinnamomi Ramulus， Poria， and Glycyrrhizae Radix et Rhizoma are the dried root of Stephania tetrandra， the dried root of Astragalus embranaceus var. mongholicus， the dried shoot of Cinnamomum cassia， the dried sclerotium of Poria cocos， and the dried root and rhizome of Glycyrrhiza uralensis， respectively. Fangji Fulingtang is mainly produced into powder， with the dosage and decocting method used in the past dynasties basically following the original formula. Each bag is composed of Stephaniae Tetrandrae Radix 13.80 g， Astragali Radix 13.80 g， Cinnamomi Ramulus 13.80 g， Poria 27.60 g， and Glycyrrhizae Radix et Rhizoma 9.20 g. The raw materials are purified， decocted in water from 1 200 mL to 400 mL， and the decoction should be taken warm， 3 times a day. Fangji Fulingtang was originally designed for treating skin edema， and then it was used to treat impediment in the Qing dynasty. In modern times， it is mostly used to treat musculoskeletal and connective tissue diseases and circulatory system diseases， demonstrating definite effects on various types of edema and heart failure. This paper clarifies the inheritance of Fangji Fulingtang and reveals its key information （attached to the end of this paper）， aiming to provide a theoretical basis for the development of preparations based on this formula.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Lung cancer exhibits the highest incidence and mortality rates among cancers globally, with a five-year overall survival rate alarmingly below 20%. Targeting autophagy, though a controversial therapeutic strategy, is extensively employed in clinical practice. Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy. Nevertheless, the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention. This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer. It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells. Notably, most autophagy-targeting drugs, primarily natural small molecules, have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer, as opposed to inhibiting protective autophagy. These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies, offering promising approaches to combat this disease.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To investigate and analyze the distribution of serum cytokeratin 19 fragment antigen 21-1(CYFRA21-1)and squamous cell carcinoma-associated antigen(SCCA)levels in healthy pregnant women during pregnancy and to assess their diagnostic value for cervical cancer in pregnancy.Methods A total of 441 healthy pregnant women and 69 patients with cervical cancer in pregnancy who attended the Obstetrics and Gynecology Hospital of Fudan University from Jan 2021 to May 2024 were selected,and 165 healthy women in the Physical Examination Center of the Obstetrics and Gynecology Hospital of Fudan University were included in the same period as the control group.The healthy pregnant women were divided into 143 in early pregnancy(T1 group),147 in middle pregnancy(T2)and 151 in late pregnancy(T3).Serum CYFRA21-1 and SCCA values were detected and analyzed in all groups.One-way ANOVA,independent samples t-test,Mann-Whitney U-test,Kruskal-Wallis H-test,logistic analysis,and ROC curves were used for comparative analysis.Results The CYFRA21-1 and SCCA values were 1.66(1.19-2.17)ng/mL and 0.8(0.6-1.0)ng/mL in the control group,3.07(2.11-4.14)ng/mL and 0.9(0.7-1.3)ng/mL in the healthy pregnant women group,and were 4.33(2.99-7.60)ng/mL and 1.8(0.9-8.5)ng/mL in the patients with cervical cancer in pregnancy group,respectively.There was a statistically significant difference in the two serum values between every two groups(P<0.05).CYFRA21-1 levels were 3.13(2.46-4.05)ng/mL,1.89(1.50-2.53)ng/mL and 4.19(3.48-5.43)ng/mL in the T1,T2,and T3 groups,respectively;and SCCA levels were 0.9(0.7-1.1)ng/mL,0.7(0.6-1.0)ng/mL and 1.2(0.8-1.7)ng/mL,respectively.The results of T1 and T3 groups were higher than those of the control group(P<0.05);however,there was no statistically significant difference between the results of the T2 group and those of the control group(P>0.05).The areas under the ROC curves for the diagnosis of cervical cancer in pregnancy for CYFRA21-1,SCCA,human epididymis protein 4(HE4),anti-carcinoembryonic antigen(CEA)and joint indicators were 0.684,0.724,0.612,0.791 and 0.913,with sensitivities of 36%,48%,38%,57%and 73%,specificities of 96%,97%,89%,86%and 99%,respectively.The cut-off values of each indicator were 6.05 ng/mL,2.60 ng/mL,51.45 pg/mL and 1.75 ng/mL,respectively.Conclusion Serum CYFRA21-1 and SCCA levels were higher in pregnant women during early and late pregnancy compared with non-pregnant individuals,while they were not statistically different from non-pregnant women during mid-trimester.CYFRA21-1 and SCCA have diagnostic value for patients with cervical cancer during pregnancy.

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applica-tions of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.

Objective To evaluate the process risk of the implementation of prevention and control measures for surgical site infection(SSI)after colorectal surgery,and explore the application effect of failure mode and effects analysis(FMEA)based on action priority.Methods FMEA based on action priority was adopted to evaluate the whole process of the implementation of prevention and control measures for SSI after colorectal surgery.Prioritiza-tion ranking was conducted according to whether optimized measures were taken.Standard-reaching rate of comp-liance to SSI prevention and control measures as well as SSI incidence before and after the implementation of FMEA were compared.Results After evaluation,there were 7 high-priority and 22 medium-priority prevention and control measures for SSI.The control of medium-priority measures was strengthened,with a focus on developing further preventive and detectable measures for high-priority measures.The re-evaluation results after improvement showed that 7 high-priority measures have been downgraded to medium priority,and 16 medium-priority measures have been downgraded to low priority.Standard-reaching rate of compliance to SSI prevention and control measures in-creased from 77.15％(2 566/3 326)to 92.47％(3 096/3 348),and SSI incidence decreased from 6.04％(58/960)to 2.54％(60/2 364).Conclusion Application of FMEA based on action priority can effectively evaluate the risk of prevention and control process of SSI after colorectal surgery,and adopting preventive risk control measures accord-ing to the current situation can reduce the incidence of SSI after colorectal surgery.