Traditional Chinese medicine （TCM） offers a rich theoretical foundation and clinical experience for the prevention and treatment of cardiovascular-kidney-metabolic syndrome（CKM）， demonstrating unique advantage. Building on previous work in managing diabetes， its complications， and chronic kidney disease， our team has proposed a five-phase evolution theory of "constraint， heat， deficiency， stasis， and toxin" as the core pathogenesis. These phases correspond to the pathological progression of constraint of phlegm-dampness， constraint transforming into heat， heat damaging qi and yin， stasis accumulated in the collateral vessels， and toxin induced by deficiency and stasis. In the prevention and treatment of CKM by TCM， it is emphasized to integrate the concept of "treating disease before it arises" with constitution theory， and incorporate the "2-5-8" prevention and treatment strategy， which combines prevention with treatment， tailors interventions to different phases， and employs comprehensive treatment modalities. Our goal is to leverage TCM's holistic advantages in preventing and treating CKM.

G protein-coupled receptors (GPCRs) are a large family of membrane protein receptors, and Takeda G protein-coupled receptor 5 (TGR5) is a member of this family. As a membrane receptor, TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism, including the processes of energy consumption, weight loss and blood glucose homeostasis. Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver, obesity and diabetes. With the global obesity situation becoming more and more serious, a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed. In this review, we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target, and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands, which can effectively provide new ideas for ligand research and promote drug research.

African swine fever virus(ASFV)I177L gene deletion vaccine is one of the key directions of African swine fever(ASF)live attenuated vaccine research and development.In order to effec-tively distinguish between the wild-type ASFV strain and the I177L gene-deleted strain,specific primers and probes were designed based on ASFV B646L and I177L genes,respectively.After screening and optimization,a duplex real-time PCR method was developed that can simultaneously detect these two genes.The results showed that ASFV B646L and I177L genes were detected spe-cifically and simultaneously by the method developed without cross-reactions with porcine circovir-us type 2,Seneca virus A,classical swine fever virus,foot-and-mouth disease virus,porcine respira-tory and reproductive syndrome virus.The detection limits of the duplex real-time PCR for recom-binant plasmids pUC57-B646L and pUC57-I177L were 1×103 copies/mL.The intra-and inter-as-say coefficients of variation were less than 4％,respectively.Detection of 122 pork and pork prod-ucts using the duplex real-time PCR developed and the real-time PCR recommended by WOAH showed that the coincidence rates of the two methods for B646L gene detection was 100％with two amplification curves appeared in the positive results of the established methods.The method established in this study can be used for the detection of ASFV I177L gene deletion strains,which provides technical support for ASF surveillance and epidemiological investigation.

Objective:To investigate the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treatment of high-risk multiple myeloma (MM) patients and its influencing factors of the prognosis.Methods:The clinical data of 44 high-risk MM patients treated with allo-HSCT in Changzheng Hospital Affiliated of Naval Military Medical University from April 2003 to March 2017 were retrospectively analyzed. The overall response rate (ORR), relapse rate, non-relapse-related death (NRM) rate, graft-versus-host disease (GVHD) incidence of patients were also analyzed. Kaplan-Meier was used to analyze the overall survival (OS) rate and progression-free survival (PFS) rate after transplantation. Cox proportional hazard model was used to make regression analysis of the factors affecting the prognosis.Results:Among 44 patients, 38 cases could be evaluated for efficacy after transplantation. The median follow-up time was 111 months (0-216) months, 22 cases survived, 22 cases died, 21 cases relapsed. Before transplantation, complete remission (CR) rate was 29.5%(13/44), very good partial remission(VGPR) rate was 45.5%(20/44), partial remission (PR) rate was 22.7% (10/44), stable disease (SD) rate was 2.3% (1/44); After transplantation, CR rate was 71.7%(27/38), VGPR rate was 13.2% (5/38), PR rate was 13.2% (5/38), the progression of the disease (PD) rate 2.6% (1/38). The 5-year OS rate and PFS rate was 51.8% and 47.8%, the 10-year OS rate and PFS rate was 51.3% and 43.1%, respectively; the 5-year and 10-year cumulative disease relapse rate was 38.6% and 45.4%, the 5-year cumulative NRM rate was 25.0%. Acute GVHD rate was 38.6% (17/44) and grade 3-4 acute GVHD rate was 6.8% (3/44); chronic GVHD rate was 27.3% (12/44). Cox univariate and multivariate analysis showed that the use of bortezomib before transplantation ( HR = 3.461, 95% CI 1.211-9.880, P = 0.020) and post-transplant infection ( HR = 0.283, 95% CI 0.098-0.819, P = 0.020) were independent factors affecting OS after transplantation. Conclusions:Allo-HSCT can overcome the high-risk factors of MM and is worth to try for high-risk MM patients. The use of bortezomib before transplantation and post-transplant infection can be important factors affecting OS after transplantation.

Objective:To investigate the treatment options for multiple myeloma patients with central nervous system involvement (CNS-MM) , as well as their clinical characteristics and prognostic factors.Methods:Between January 2011 and January 2022 our center diagnosed 18 people with CNS-MM. A retrospective analysis was done on the clinical information from the initial diagnosis and central nervous system involvement, and it was compared to 1∶3 matched newly diagnosed MM from the same period. Analysis was done on the clinical characteristics and survival rates of the two groups.Results:In patients with CNS-MM, the median time of onset was 14.2 (0.9-79.6) months and the median overall survival (OS) was 30.5 months from initial diagnosis and only 3.8 months in patients after CNS involvement. The CNS-MM patients showed more IgD type ( P=0.010) , severer anemia ( P=0.014) , a higher proportion of bone marrow plasma cells ( P=0.013) , more extramedullary lesions ( P=0.001) , and increased lactic dehydrogenase (LDH) ( P=0.009) when compared to the control group. Lenalidomide or pomalidomide-based combinations had higher rates of hematology and CNS remission than bortezomib or daratumumab-based regimens (75.0% vs 16.7% , P=0.019) . Patients who received IMiD-based regimens and had 2 high-risk factors at initial diagnosis (high LDH and extramedullary lesions) had a significantly lower incidence of CNS-MM ( P=0.026) . At the initial diagnosis, LDH ( P=0.008, HR=7.319, 95% CI 1.663-32.219) and extramedullary lesions ( P=0.006, HR=8.054, 95% CI 1.828-35.486) were independent risk factors for the occurrence of CNS-MM. Conclusion:Patients with CNS-MM had a poor prognosis. Patients with high LDH or extramedullary lesions at the time of the initial diagnosis are more likely to have CNS-MM. The prognosis of this patient may be improved by immunoregulator-based therapy.

Objective:To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM) .Methods:The clinical characteristics, adverse reactions, efficacy, and prognosis of 46 patients with RRMM treated with daratumumab in Shanghai Changzheng Hospital from September 2017 to March 2020 were retrospectively analyzed.Results:All patients were treated with daratumumab-based regimen: 8 in the Dd group, 35 in the DRd group, and 3 in the DVd group. With a median follow-up of 9.6 months, the overall response rate (ORR) was 75% [complete remission (CR) rate 18.2% ] among the 44 patients available for evaluation. The ORRs of patients resistant to bortezomib, lenalidomide, and both were 70.6% , 69.2% , and 63.6% , respectively. The CR rates of patients resistant to bortezomib, lenalidomide, and both were 17.6% , 11.5% , and 13.6% , respectively. No significant difference was observed in ORR and CR rates among the three groups. The ORRs of the DRd, DVd, and Dd groups were 85.3% , 66.7% , and 28.6% , respectively ( P=0.007) . The median PFS of 46 patients was 8.9 months, the median OS was not reached, and the 1-year OS rate was 74% . The median PFS and OS in the DRd group were longer than those in the Dd group (PFS: 14.4 months vs 2.0 months; OS: not reached vs 5.2 months) . After treatment with daratumumab, neutropenia is the most common hematological adverse reaction above grade 3. Non-hematological adverse reactions are mainly infusion-related adverse reactions and infections. Prognostic analysis showed that patients with extramedullary invasion had shorter PFS and OS compard with patients without extramedullary invasion (PFS: 5.7 vs 14.4 months, P=0.033; OS: 6.3 months vs not reached, P=0.029) . The OS of patients with an ECOG score of 3-4 was significantly shorter than patients with an ECOG score of 1-2 (5.9 months vs not reached, P=0.004) . Conclusion:Daratumumab-based regimens have good efficacy and safety in the treatment of RRMM.

Objective:To summarize the clinical characteristics and prognosis of 51 patients with Waldenstr?m’s macroglobulinemia (WM) and evaluate the efficacy and adverse reactions of ibrutinib in the treatment of WM.Methods:We carried out a single-center retrospective study, including 51 patients with WM of our single center from November 2008 to October 2019.Results:The median age at diagnosis was 65 years with a male-to-female ratio of 2.64∶1. There were 9 (18%) , 21 (41%) , and 21 (41%) ISSWM stage low-, intermediate- and high-risk patients identified, respectively. A total of 27 (73%) patients harbored MYD88 L265P mutation. The median follow-up time was 38.6 (0.3-120.0) months, the median progression free survival was 46.4 months, and the median overall survival was not reached. The overall remission and major remission rates of patients who received ibrutinib were 87% and 80%, respectively. The median time to achieve at least partial remission of patients treated with ibrutinib was 8 weeks, which was earlier than those treated with other drugs ( P<0.05) . Conclusion:WM is often seen in elderly men. MYD88 L265P had a high frequency in WM. The findings of our study validate the efficacy of ibrutinib monotherapy. Even in patients with advanced age and at high risk of ISSWM, the overall remission rate and major remission rate are high. Ibrutinib is a safe and effective therapy because of its rapid onset and rare serious adverse reactions.

Objective: To evaluate the prognostic value of serum free light chain ratio (rFLC) and difference (dFLC) in patients with multiple myeloma (MM) . Methods: Clinical data of 479 cases of newly diagnosed MM patients with FLC test records referred to our hospital from January 2012 to March 2016 were collected. rFLC preferred cut-off values were selected as≤14.828,14.828-364.597, ≥364.597 according to the literatures. The dFLC was divided into ≤112.85,112.85-2891.83, ≥2891.83 mg/L three groups. The rFLC and dFLC values among the death, the non-death, the progress and the non-progress groups were compared by t test. The correlation analysis showed that the rFLC and dFLC values were related to the death or progression of the disease. Logistic regression was used to analyze the correlation between each factor and death or progression. Univariate survival analysis (PFS) and total survival (OS) were performed using Kaplan-Meier. Single-variable and multivariate prognostic analysis were performed using Cox model. Results: The cutoff values of rFLC less than 14.828 or dFLC less than or equal to 112.85 mg/L impacted most significant on OS and PFS of the patients (P<0.05) . Different rFLC cut-off values between two groups showed that when rFLC=14.828, OS was significantly better than the other two groups (NR vs 61 & 47 months, P=0.019) ; different dFLC cut-off values between two groups disclosed that PFS and OS were statistically significant when dFLC less than or equal to 112.85 mg/L compared with the other two groups (P<0.05) . The 4-year PFS/OS rates in the initial dFLC≤112.85 mg/L and rFLC≤14.828 groups was significantly higher than of the other two groups. Conclusion Different cutoff levels of rFLC and dFLC might have obviously effects on the prognoses of patients with newly diagnosed MM. The difference of survival prognosis would be more pronounced when rFLC≤14.828 or dFLC≤112.85 mg/L with lower risk of death and lower risk ratio, which might be ideal cutoff value for determining the prognosis of these patients.

Objective: To analyze the significance of serum free light chain (sFLC) for the prognosis of the patients with newly diagnosed multiple myeloma (NDMM). Methods: The clinical data of 621 NDMM patients in Changzheng Hospital from June 2010 to December 2016 was retrospectively analyzed. The serum free light chain levels were measured and the ratios of κ/λ chains were calculated. The significance of serum free light chain ratio (sFLCR) for the prognosis of NDMM patients was analyzed. Results: Among the 621 NDMM patients, 42 patients (6.8%) were in the normal free light chain ratio group (0.26≤sFLCR≤1.65), 247 patients (39.8%) were in the low free light chain ratio group (0.01＜sFLCR＜0.26 or 1.65＜sFLCR＜100), and 332 patients (53.5%) were in the high free light chain ratio group (sFLCR≤0.01 or sFLCR≥100). Compared with normal sFLCR group, the abnormal sFLCR group showed low level of hemoglobin; elevated levels of bone marrow plasma cells, serum creatinine and β 2 -MG, and more patients were in DS stage Ⅲ and ISS stage Ⅲ with high risks of cytogenetics(all P＜0.05). The overall survival (OS) in the normal sFLCR group was significantly better than the abnormol sFLCR groups (not reached vs 58.7 months, P=0.043). Compared with the patients with both high sFLCR and low risks of cytogenetics, the patients with high sFLCR and high risks of cytogenetics showed shorter overall survival time (median OS time was 41.6 months vs 61.4 months, P=0.015). Conclusion The NDMM patients with significantly abnormal sFLCR may indicate more tumor load and higher aggressive progression. sFLCR should be an independent prognostic indicator for the outcome of multiple myeloma. The patients with high sFLCR and cytogenetic abnormalities, have worse prognosis than the others.

Objective To analyze the diagnostic value of multicolor scanning laser imaging (confocal scanning laser ophthalmoscopy, cSLO) combined with swept-source optical coherence tomography (SS-OCT) for lacquer cracks (LC) and myopia stretch lines (MSL) of pathological myopia.Methods A observational study. A total of 83 eyes of 58 patients with pathological myopia were recruited from May 2017 to January 2018 in Department of Ophthalmology of The First People's Hospital Affiliated to Shanghai Jiao Tong University. Among 58 patients, 20 were males (30 eyes) and 38 were females (53 eyes). The mean age was 50.65±12.02 (range from 24 to 70) years old; the average BCVA was 0.37±0.32; the average diopter was?11.38±4.96 D; and the average axial length was 28.91±2.15 mm. All participants underwent FFA and ICGA examination to obtain FFA, ICGA, infrared light reflection (IR) and autofluorescence (AF) images. SS-OCT was applied for scanning macular and optic disc at 9 mm× 9 mm range. cSLO was performed with macular as the center. All images were inspected carefully by three independent observers and the consistency test was detect. LC were diagnosed as hyperreflective line in FFA and hypofluorescent linear lesions in late ICGA. MSL were defined as both hypofluorescent linear lesions in FFA and late ICGA. The accuracy of each inspection item in the diagnosis of LC was detected. The optimal technique was applied with SS-OCT to further explore the detection rate of LC.Results The intra-observer reproducibility was good to excellent for all measurements (Kappa=0.938,P<0.01). The positive detection rate of LC and MSL was highest in the standard images of cSLO (77.1％), followed by SS-OCT red free (73.1％), fundus photography (72.3％), IR (72.3％) and AF (49.4％). The cSLO was optimal in the test consistency (Kappa=0.520,P<0.01) and accuracy (the area under the receiver operating characteristic was 0.750). SS-OCT and cSLO were jointly applied to diagnosis of LC and MSL in high myopia. The positive detection rate of LC, MSL and LC+MSL were 91.7％, 91.2％ and 93.3％respectively. The characteristics of LC in SS-OCT were irregularities and discontinuous of the RPE-Bruch membrane line, discontinuous inner ellipsoid zone, thinner choroid, an increased light penetrance into deeper tissues, and RPE fracture in severe cases. MSL was mainly manifested as RPE clumps, visible large choroidal vessels protruding and pushing the overlying RPE toward the vitreous.Conclusions The diagnosis rate of LC in pathological myopia by cSLO is 77.1％. The standard images of cSLO combined with SS-OCT can diagnose LC, MSL and LC+MSL at rates of 91.7％, 91.2％ and 93.3％ respectively.