Objective To summarize the clinical and genetic characteristics of children with sodium taurocholate co-transporting polypeptide(NTCP)deficiency.Methods Clinical data of children with NTCP deficiency diagnosed and treated at the First People's Hospital of Yunnan Province from July 2022 to March 2025 were retrospectively analyzed.Results A total of 14 children were included(6 males,8 females),all with normal growth and development.Reasons for initial consultation included elevated serum bile acids in 7 cases,jaundice in 4 cases,cholestatic hepatitis in 1 case,and one case each of pneumonia and cow's milk protein allergy.At the first visit,all patients had elevated serum total bile acids beyond the normal range,with a mean of 152.5 μmol/L.Elevated alanine aminotransferase was observed in 1 case,elevated aspartate aminotransferase in 2 cases,and elevated total bilirubin in 10 cases.Genetic sequencing revealed that all children carried the homozygous SLC10A1 variant c.800C>T(p.Ser267Phe),classified as likely pathogenic.Conclusions NTCP deficiency often lacks obvious clinical symptoms and signs.Some children present with transient hyperbilirubinemia,cholestasis,or other liver function abnormalities.Persistent isolated elevation of serum bile acids warrants suspicion for this disease.Biallelic pathogenic variants in SLC10A1 constitute the basis for definitive diagnosis.There is no specific treatment for this disease,and management is mainly symptomatic.

AIM To explore the clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 6-week intervention of conventional treatment,and observation group(60 cases)for 6-week intervention of both Supplemented Buyang Huanwu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,spinal cord conduction signals(SEP amplitude,MEP amplitude),serum neurotrophic factors(NGF,IGF-1,BDNF),coagulation and inflammatory indices(PT,APTT,TNF-α,IL-1 β)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,TNF-α,IL-1β(P＜0.05),increased spinal cord conduction signals,coagulation and inflammatory indices(P＜0.05),and shortened PT,APTT(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern,Supplemented Buyang Huanwu Decoction can safely and effectively promote neurological function recovery.

Objective To summarize the clinical and genetic characteristics of children with sodium taurocholate co-transporting polypeptide(NTCP)deficiency.Methods Clinical data of children with NTCP deficiency diagnosed and treated at the First People's Hospital of Yunnan Province from July 2022 to March 2025 were retrospectively analyzed.Results A total of 14 children were included(6 males,8 females),all with normal growth and development.Reasons for initial consultation included elevated serum bile acids in 7 cases,jaundice in 4 cases,cholestatic hepatitis in 1 case,and one case each of pneumonia and cow's milk protein allergy.At the first visit,all patients had elevated serum total bile acids beyond the normal range,with a mean of 152.5 μmol/L.Elevated alanine aminotransferase was observed in 1 case,elevated aspartate aminotransferase in 2 cases,and elevated total bilirubin in 10 cases.Genetic sequencing revealed that all children carried the homozygous SLC10A1 variant c.800C>T(p.Ser267Phe),classified as likely pathogenic.Conclusions NTCP deficiency often lacks obvious clinical symptoms and signs.Some children present with transient hyperbilirubinemia,cholestasis,or other liver function abnormalities.Persistent isolated elevation of serum bile acids warrants suspicion for this disease.Biallelic pathogenic variants in SLC10A1 constitute the basis for definitive diagnosis.There is no specific treatment for this disease,and management is mainly symptomatic.

AIM To explore the clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 6-week intervention of conventional treatment,and observation group(60 cases)for 6-week intervention of both Supplemented Buyang Huanwu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,spinal cord conduction signals(SEP amplitude,MEP amplitude),serum neurotrophic factors(NGF,IGF-1,BDNF),coagulation and inflammatory indices(PT,APTT,TNF-α,IL-1 β)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,TNF-α,IL-1β(P＜0.05),increased spinal cord conduction signals,coagulation and inflammatory indices(P＜0.05),and shortened PT,APTT(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern,Supplemented Buyang Huanwu Decoction can safely and effectively promote neurological function recovery.

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Objective To investigate the regulatory effect and possible mechanism of lactic acid on the fibrotic phenotype of cardiac fibroblasts.Methods Mouse cardiac fibroblasts(mCFs)were divided into control group(conventional culture),experimental-L group(4 mmol·L-1 L-lactic acid),experimental-M group(8 mmol·L-1 L-lactic acid),experimental-H group(12 mmol·L-1 L-lactic acid),transforming growth factor-β1(TGF-β1)group(10 ng·mL-1 TGF-β1),combined group(10 ng·mL-1 TGF-β1+12 mmol·L-1 L-lactic acid)and monocarboxylate transporter inhibitor(CHC)group(3 mmol·L-1 CHC).Western blot was used to detect the expression of fibrosis-related proteins and pan-lactate modification(Pan Kla)and H3 histone K18 lactate modification;cell scratch assay was used to detect cell migration ability.Results The cell migration rates of the control group,TGF-β1 group,experimental-H group and combined group were(40.56±0.03)％,(61.61±0.04)％,(26.59±0.05)％and(38.33±0.06)％,respectively.Compared with the control group,TGF-β1 group and experimental-H group,TGF-β1 group and combined group,the differences were statistically significant(all P＜0.01).The relative expression levels of collagen type Ⅰ alpha 1(COL1A1)protein in the control group,TGF-β1 group,experimental-H group and TGF-β1+experimental-H group were 0.76±0.09,1.10±0.07,0.40±0.04 and 0.68±0.10,respectively;the relative expression levels of COL3A1 protein were 0.87±0.05,1.15±0.07,0.32±0.07 and 0.73±0.06,respectively;the relative expression levels of α-smooth muscle actin(α-SMA)protein were 0.86±0.04,1.24±0.09,0.30±0.05 and 0.74±0.08,respectively.Compared with the control group,the above indexes of the TGF-β1 group and the experimental-H group were significantly different from those of the control group,and the above indexes of the TGF-β1 group were significantly different from those of the combined group(all P＜0.01).The cell migration rates of mCFs in the control group,experimental-H group and CHC group were(62.60±6.50)％,(28.00±8.15)％and(39.40±4.50)％,respectively;the relative expression levels of COL1A1 protein were 1.10±0.07,0.49±0.04 and 0.34±0.06,respectively;the relative expression levels of COL3A1 protein were 1.04±0.10,0.60±0.20 and 0.37±0.03,respectively;the relative expression levels of α-SMA protein were 1.20±0.11,0.67±0.20 and 0.48±0.18,respectively;the modification levels of Pan Kla were 1.06±0.07,1.54±0.09 and 1.53±0.12,respectively;the modification levels of H3K18la protein were 0.67±0.06,1.23±0.06 and 1.14±0.08,respectively.The above indexes of CHC group and experimental-H group were significantly different from those of control group(all P＜0.01).Conclusion L-lactic acid may play a role in inhibiting the fibrosis phenotype of mCFs by increasing non-histone lactic acid modification and H3K18la modification.

Objective To investigate the regulatory effect and possible mechanism of lactic acid on the fibrotic phenotype of cardiac fibroblasts.Methods Mouse cardiac fibroblasts(mCFs)were divided into control group(conventional culture),experimental-L group(4 mmol·L-1 L-lactic acid),experimental-M group(8 mmol·L-1 L-lactic acid),experimental-H group(12 mmol·L-1 L-lactic acid),transforming growth factor-β1(TGF-β1)group(10 ng·mL-1 TGF-β1),combined group(10 ng·mL-1 TGF-β1+12 mmol·L-1 L-lactic acid)and monocarboxylate transporter inhibitor(CHC)group(3 mmol·L-1 CHC).Western blot was used to detect the expression of fibrosis-related proteins and pan-lactate modification(Pan Kla)and H3 histone K18 lactate modification;cell scratch assay was used to detect cell migration ability.Results The cell migration rates of the control group,TGF-β1 group,experimental-H group and combined group were(40.56±0.03)％,(61.61±0.04)％,(26.59±0.05)％and(38.33±0.06)％,respectively.Compared with the control group,TGF-β1 group and experimental-H group,TGF-β1 group and combined group,the differences were statistically significant(all P＜0.01).The relative expression levels of collagen type Ⅰ alpha 1(COL1A1)protein in the control group,TGF-β1 group,experimental-H group and TGF-β1+experimental-H group were 0.76±0.09,1.10±0.07,0.40±0.04 and 0.68±0.10,respectively;the relative expression levels of COL3A1 protein were 0.87±0.05,1.15±0.07,0.32±0.07 and 0.73±0.06,respectively;the relative expression levels of α-smooth muscle actin(α-SMA)protein were 0.86±0.04,1.24±0.09,0.30±0.05 and 0.74±0.08,respectively.Compared with the control group,the above indexes of the TGF-β1 group and the experimental-H group were significantly different from those of the control group,and the above indexes of the TGF-β1 group were significantly different from those of the combined group(all P＜0.01).The cell migration rates of mCFs in the control group,experimental-H group and CHC group were(62.60±6.50)％,(28.00±8.15)％and(39.40±4.50)％,respectively;the relative expression levels of COL1A1 protein were 1.10±0.07,0.49±0.04 and 0.34±0.06,respectively;the relative expression levels of COL3A1 protein were 1.04±0.10,0.60±0.20 and 0.37±0.03,respectively;the relative expression levels of α-SMA protein were 1.20±0.11,0.67±0.20 and 0.48±0.18,respectively;the modification levels of Pan Kla were 1.06±0.07,1.54±0.09 and 1.53±0.12,respectively;the modification levels of H3K18la protein were 0.67±0.06,1.23±0.06 and 1.14±0.08,respectively.The above indexes of CHC group and experimental-H group were significantly different from those of control group(all P＜0.01).Conclusion L-lactic acid may play a role in inhibiting the fibrosis phenotype of mCFs by increasing non-histone lactic acid modification and H3K18la modification.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Five new terpenoids, including two vibsane-type diterpenoids (1, 2) and three iridoid allosides (3-5), together with eight known ones, were isolated from the leaves and twigs of Viburnum odoratissimum var.sessiliflorum. Their planar structures and relative configurations were determined by spectroscopic methods, especially 2D NMR techniques. The sugar moieties of the iridoids were confirmed as β-D-allose by GC analysis after acid hydrolysis and acetylation. The absolute configurations of neovibsanin Q (1) and dehydrovibsanol B (2) were determined by quantum chemical calculation of their theoretical electronic circular dichroism (ECD) spectra and Rh₂(OCOCF₃)₄-induced ECD analysis. The anti-inflammatory activities of compounds 1, 3, 4, and 5 were evaluated using an LPS-induced RAW264.7 cell model. Compounds 3suppressed the release of NO in a dose-dependent manner, with an IC₅₀ value of 55.64 μmol·L^-1. The cytotoxicities of compounds 1-5 on HCT-116 cells were assessed and the results showed that compounds 2 and 3 exhibited moderate inhibitory activities with IC₅₀ values of 13.8 and 12.3 μmol·L^-1, respectively.
Terpenes/pharmacology* ; Viburnum/chemistry* ; Molecular Structure ; Diterpenes/chemistry* ; Plant Leaves/chemistry*

With the continuous exploration of microemulsions as solvents for traditional Chinese medicine extraction, polyoxyethy-lene(35) castor oil(CrEL), a commonly used surfactant, is being utilized by researchers. However, the problem of detecting residues of this surfactant in microemulsion extracts has greatly hampered the further development of microemulsion solvents. Based on the chemical structures of the components in CrEL and the content determination method of castor oil in the 2020 edition of the Chinese Pharmacopoeia(Vol. Ⅳ), this study employed gas chromatography(GC) and single-factor experiments to optimize the preparation method of methyl ricinoleate from CrEL. The conversion coefficient between the two was validated, and the optimal sample preparation method was used to process microemulsion extracts of Zexie Decoction from three batches. The content of methyl ricinoleate generated was determined, and the content of CrEL in the microemulsion extracts of Zexie Decoction was calculated using the above conversion coefficient. The results showed that the optimal preparation method for CrEL was determined. Specifically, 10 mL of 1 mol·L~(-1) KOH-methanol solution was heated at 60 ℃ for 15 min in a water bath. Subsequently, 10 mL of boron trifluoride etherate-methanol(1∶3) solution was heated at 60 ℃ for 15 min in a water bath, followed by extraction with n-hexane twice. CrEL could stably produce 20.84% methyl ricinoleate. According to this conversion coefficient, the average mass concentration of CrEL in the three batches of Zexie Decoction microemulsion extracts was 11.94 mg·mL~(-1), which was not significantly different from the CrEL mass concentration of 11.57 mg·mL~(-1) during microemulsion formulation, indicating that the established content determination method of this study was highly accurate, sensitive, and repeatable. It can be used for subsequent research on microemulsion extracts of Zexie Decoction and provide a reference for quality control of other drug formulations containing CrEL.
Polyethylene Glycols/chemistry* ; Castor Oil ; Methanol ; Surface-Active Agents/chemistry* ; Solvents ; Water/chemistry* ; Emulsions/chemistry*