To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Hepatic fibrosis is a reversible pathological process in various chronic liver diseases and is closely associated with the development and progression of severe liver diseases such as liver cirrhosis and hepatocellular carcinoma， and it has emerged as a significant global health challenge. In recent years， studies have shown that histone lactylation， a newly discovered epigenetic modification， actively participates in regulating the progression of hepatic fibrosis. This article systematically reviews the core regulatory effect of histone lactylation modification in the interaction between inflammatory microenvironment and hepatic fibrosis， in order to clarify the cascade regulatory mechanism of “inflammation-hepatic fibrosis” and provide new insights for early diagnosis， targeted intervention， and prevention of malignant transformation in hepatic fibrosis.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature

Objective:To investigate the effect of Xuebijing injection against blood-brain barrier(BBB)damage in the mice with anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis,and to elucidate its regulatory effect on the imbalance of helper T cells 17(Th17)/regulatory T cells(Treg).Methods:The active immunization models of anti-NMDAR encephalitis in the mice were established using glutamate receptor N1 subunit(GluN1)356-385 antigen peptide,and the serum anti-NMDAR immunoglobulin G(IgG)antibody levels were detected by enzyme-linked immunosorbent assay(ELISA).The healthy mice without modeling were served as control group,and the mice with successful modeling were randomly divided into model group,low dose of Xuebijing injection(XBJ-L)group,and high dose of Xuebijing injection(XBJ-H)group,with 10 mice in each group.After modeling,the mice in XBJ-L and XBJ-H groups were intraperitoneally injected with 5 and 10 mL·kg-1 Xuebijing injection,respectively.The Longa score was used to assess the neurological impairment of the mice in various groups;evans blue(EB)staining was used to determine the BBB permeability;immunofluorescence staining was used to detect the expressions of zonula occludens 1(ZO-1)and Occludin in cerebral cortex of the mice in various groups;Western blotting method was used to determine the expression levels of ZO-1,Occludin,Claudin-5,and neuron-specific nuclear protein(NeuN)in cerebral cortex of the mice in various groups;ELISA method was used to determine the levels of Th17-and Treg-related cytokines including interleukin(IL)-17,IL-22,and IL-10 in serum of the mice;flow cytometry was used to determine the percentages of Th17 and Treg cells in peripheral blood of the mice in various groups,and the Th17/Treg ratio was calculated.Results:The serum of the mice induced with the GluN1 356-385 antigen peptide was positive for NMDAR IgG antibodies,indicating that the models were successfully established.Compared with control group,the neurological impairment score of the mice in model group was significantly increased(P＜0.05),and the EB level in brain tissue was significantly increased(P＜0.05);the fluorescence staining intensities of ZO-1 and Occludin in the cerebral cortex were decreased,and the expression levels of ZO-1,Occludin,Claudin-5,and NeuN proteins in the cerebral cortex were significantly decreased(P＜0.05);the serum levels of IL-17 and IL-22 were significantly increased(P＜0.05),while the IL-10 level was significantly decreased(P＜0.05);the percentage of Th17 cells in peripheral blood was significantly increased(P＜0.05),while the percentage of Treg cells was significantly decreased(P＜0.05),and the Th17/Treg ratio was significantly increased(P＜0.05).Compared with model group,the neurological impairment scores of the mice in XBJ-L and XBJ-H groups were significantly decreased(P＜0.05),the EB levels in brain tissue were significantly decreased(P＜0.05),the fluorescence staining intensities of ZO-1 and Occludin in cerebral cortex were increased,and the expression levels of ZO-1,Occludin,Claudin-5,and NeuN proteins were significantly increased(P＜0.05);the levels of IL-17 and IL-22 in serum were significantly decreased(P＜0.05),and the level of IL-10 was significantly increased(P＜0.05);the percentages of Th17 cells in peripheral blood were significantly decreased(P＜0.05),the percentages of Treg cells were significantly increased(P＜0.05),and the Th17/Treg ratios were significantly decreased(P＜0.05).Compared with XBJ-L group,the neurological function injury score of the mice in XBJ-H group was significantly decreased(P＜0.05),the EB level in brain tissue was significantly decreased(P＜0.05);the fluorescence staining intensities of ZO-1 and Occludin in the cerebral cortex were increased,and the expression levels of ZO-1,Occludin,Claudin-5,and NeuN proteins were significantly increased(P＜0.05);the serum levels of IL-17 and IL-22 were significantly decreased(P＜0.05),and the level of IL-10 was significantly increased(P＜0.05);the percentage of Th17 cells in peripheral blood was significantly decreased(P＜0.05),the percentage of Treg cells was significantly increased(P＜0.05),and the Th17/Treg ratio was significantly decreased(P＜0.05).Conclusion:Xuebijing injection can improve BBB injury,regulate Th17/Treg balance,and thereby alleviate the neurological functional damage in anti-NMDAR encephalitis.

OBJECTIVE: To observe the efficacy and safety of 21-day venetoclax (VEN) plus azacitidine (AZA) (21-day VA) in newly diagnosed unfit acute myeloid leukemia (AML) patients in the real-world. METHODS: The clinical data of patients with unfit-AML who received 21-day VA regimen from December 2020 to July 2024 in our center and completed at least 1 cycle of therapeutic effect assessment was retrospectively collected to analyze the safety, efficacy and its influencing factors. RESULTS: A total of 59 patients were enrolled in our study, with a median age of 67(48-87) years old. After 1 cycle of therapy, the composite complete remission (cCR) rate was 74.5%, 54.2% of cases were negative for minimal residual disease (MRD). Among them, the MRD negative rate of patients with NPM1 mutation was significantly higher than that of patients without NPM1 mutation ( P =0.032). The median follow-up of patients was 19(2-38) months, the best cCR and MRD negative rates were 78% and 64.4%, respectively, the median overall survival (OS) time was 12 months, and the median progression free survival (PFS) time was 5 months. Multivariate Cox regression analysis showed less than 4 cycles of VA chemotherapy were independent risk factor for PFS and OS ( P < 0.05). After achieving remission, anemia and thrombocytopenia improved with the increase of the number of chemotherapy cycle. CONCLUSION In real-world, 21-day VA regimen still shows significant efficacy in the treatment of newly diagnosed unfit-AML, without adversely affecting remission rate and MRD negative rate of the first cycle.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Aged ; Middle Aged ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Azacitidine/therapeutic use* ; Aged, 80 and over ; Male ; Female ; Retrospective Studies ; Nucleophosmin ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Remission Induction ; Mutation ; Treatment Outcome