ObjectiveTo observe the clinical efficacy of Shentong Zhuyutang combined with Dilongtang in the treatment of lumbar disc herniation （LDH） with Qi stagnation and blood stasis syndrome， and its effect on nucleus pulposus reabsorption and immune-inflammatory factors， exploring its therapeutic mechanism from the perspective of reabsorption. MethodsA total of 120 patients with LDH from the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine， treated between June 2020 and January 2023， were randomly divided into the control group （52 cases， with 8 dropouts） and the observation group （49 cases， with 11 dropouts） according to a random number table. The control group received routine treatment， while the observation group was treated with Shentong Zhuyutang combined with Dilongtang in addition to routine treatment. Visual Analogue Scale （VAS）， Oswestry Disability Index （ODI）， Japanese Orthopaedic Association （JOA） score， and traditional Chinese medicine （TCM） syndrome score were measured before treatment and after 3 courses of treatment. Venous blood samples were collected for the determination of serological indexes. MR examination was performed during the 6-month follow-up to calculate the absorption rate. ResultsAfter treatment， both groups showed significant reductions in VAS， ODI， TCM syndrome score， serum tumor necrosis factor （TNF）-α， matrix metalloproteinase （MMP）-9， and vascular endothelial growth factor （VEGF） levels， and a significant increase in JOA score compared with pre-treatment values （P<0.05）. Compared with the control group， the observation group showed significantly lower VAS， ODI， TCM syndrome score， serum TNF-α， MMP-9， and VEGF levels， and a significantly higher JOA score （P<0.05）. The proportion of nucleus pulposus reabsorption in the observation group was 57.14% （28/49）， significantly higher than 21.15% （11/52） in the control group （χ²=6.161， P<0.05）. ConclusionShentong Zhuyutang combined with Dilongtang can effectively relieve pain， improve lumbar function， and alleviate TCM clinical symptoms in LDH patients with Qi stagnation and blood stasis syndrome. Imaging findings suggest that the treatment promotes the reabsorption of nucleus pulposus protrusion， while laboratory testing shows reduced serum levels of TNF-α， MMP-9， and VEGF， which contribute to the rehabilitation of patients.

Bone marrow suppression is one of the common adverse reactions to radiotherapy and chemotherapy. Anticancer treatments such as radiotherapy and chemotherapy first directly damage the patient′s peripheral blood cells, impairing qi and blood; further, they damage the actively proliferating cell populations in the bone marrow, impairing yin and blood; and then they interfere with hematopoietic stem cells, impairing essence and blood. This process is rapid and intense, consistent with the characteristics of " acute deficiency syndrome" , marked by sudden onset, rapid changes, critical condition, complexity and variability, multiple complications, and poor prognosis. Given this, its diagnosis and treatment should differ from those of general deficiency syndromes. This paper advocates the principles and ideas of diagnosis and treatment such as " preventing first and treating early to prevent changes; supplementing for deficiency and strengthening vital qi to eliminate pathogenic factor; urgent rescue for critical conditions, no time to lose; and comprehensive supplementing throughout the process, with severe cases requiring singular action" . This approach is intended to provide theoretical reference and practical guidance for bone marrow suppression after radiotherapy and chemotherapy.

BACKGROUND: The mechanisms distinguishing metabolically healthy from unhealthy phenotypes within the same BMI categories remain unclear. This study aimed to investigate the associations between regional fat distribution and metabolically unhealthy phenotypes in Chinese adults across different BMI categories. METHODS: This cross-sectional study involving 11833 Chinese adults aged 20 years and older. Covariance analysis, adjusted for age, compared the percentage of regional fat (trunk, leg, or arm fat divided by whole-body fat) between metabolically healthy and unhealthy participants. Trends in regional fat percentage with the number of metabolic abnormalities were assessed by the Jonckheere-Terpstra test. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated by logistic regression models. All analyses were performed separately by sex. RESULTS: In non-obese individuals, metabolically unhealthy participants exhibited higher percent trunk fat and lower percent leg fat compared to healthy participants. Additionally, percent trunk fat increased and percent leg fat decreased with the number of metabolic abnormalities. After adjustment for demographic and lifestyle factors, as well as BMI, higher percent trunk fat was associated with increased odds of being metabolically unhealthy [highest vs. lowest quartile: ORs (95%CI) of 1.64 (1.35, 2.00) for men and 2.00 (1.63, 2.46) for women]. Conversely, compared with the lowest quartile, the ORs (95%CI) of metabolically unhealthy phenotype in the highest quartile for percent arm and leg fat were 0.64 (0.53, 0.78) and 0.60 (0.49, 0.74) for men, and 0.72 (0.56, 0.93) and 0.46 (0.36, 0.59) for women, respectively. Significant interactions between BMI and percentage of trunk and leg fat were observed in both sexes, with stronger associations found in individuals with normal weight and overweight. CONCLUSIONS Trunk fat is associated with a higher risk of metabolically unhealthy phenotype, while leg and arm fat are protective factors. Regional fat distribution assessments are crucial for identifying metabolically unhealthy phenotypes, particularly in non-obese individuals.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Adipose Tissue ; Body Fat Distribution ; Body Mass Index ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Phenotype

Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Objective:To explore the effect of necroptosis inhibitor necrosulfonamide (NSA) on traumatic brain injury (TBI) mouse model and BV2 cell pyroptosis model and their mechanisms.Methods:(1) In vivo experiments: 50 mice were randomly divided into sham-operated group, TBI group, TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group, with 10 mice in each group. TBI model was established using a modified Feeney's weight-drop method; 4 h after modeling, 90% corn oil, 1 mg/kg NSA, 5 mg/kg NSA, or 10 mg/kg NSA was administered into the mice, respectively. Mice in the sham-operated group only had circular bone window opened without being subjected to impact. At 48 hours after modeling, neurological function was evaluated by modified neurological function score (mNSS), serum lactate dehydrogenase (LDH) content was detected by LDH detection kit, contents of interleukin (IL)-18, IL-1β and tumor necrosis factor-α (TNF-α) in the brain tissues were detected by enzyme-linked immunosorbent assay (ELISA), and expressions and localizations of ionized calcium binding adaptor molecule 1 (IBA-1), cysteinyl aspartate specific proteinase-1 (Caspase-1) p20 and gasdermin D (GSDMD) in the injured parietal cortex were detected by double immunofluorescent staining. (2) In vitro experiments: BV2 cells were divided into control group, lipopolysaccharide (LPS)+adenosine triphosphate (ATP)+dimethyl sulfoxide (DMSO) group, LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group. Cells in the latter 4 groups were induced by LPS+ATP to establish BV2 cell pyroptosis model, and incubated with 2 μL DMSO, 5 μmol/L NSA, 10 μmol/L NSA, and 15 μmol/L NSA for 1 hour, respectively; cells in the control group were cultured conventionally. Contents of LDH, IL-1β, IL-18, and TNF-α in the cell culture supernatant were detected by ELISA; pyroptosis was detected by calcein acetoxymethyl ester (CAM)/propidium iodide (PI) double staining; protein expressions of nucleotide binding domain-like receptor protein 3 (NLRP3), Caspase-1 p20, GSDMD, and N-terminal fragment of GSDMD (GSDMD-N) were detected by Western blotting. Results:(1) Compared with the TBI group, the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had decreased mNSS score and serum LDH content, decreased IL-1β and IL-18 contents in the brain tissues and number of Caspase-1 p20 + cells in the injured parietal cortex, successively, with significant differences ( P<0.05). Compared with the TBI group ([287.80±12.26] cells/mm 2), the TBI+1 mg/kg NSA group, TBI+5 mg/kg NSA group, and TBI+10 mg/kg NSA group had decreased number of Iba-1 +GSDMD + cells in the injured parietal cortex ([213.70±11.87] cells/mm 2, [205.30±9.15] cells/mm 2, [131.70±13.69] cells/mm 2),successively, with significant differences ( P<0.05). Compared with the TBI group, the TBI+5 mg/kg NSA group and TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 + cells in the injured parietal cortex, and the TBI+10 mg/kg NSA group had significantly decreased TNF-α content in the brain tissues and number of GSDMD + cells in the injured parietal cortex ( P<0.05). Compared with the TBI group ([247.20±9.88] cells/mm 2), the TBI+10 mg/kg NSA group had significantly decreased number of Iba-1 +Caspase-1 p20 + cells in the injured parietal cortex ([181.70±9.37] cells/mm 2, P<0.05). (2) Compared with the LPS+ATP+DMSO group, the LPS+ATP+5 μmol/L NSA group, LPS+ATP+10 μmol/L NSA group, and LPS+ATP+15 μmol/L NSA group had decreased IL-18 content in the supernatant, successively, with significant differences ( P<0.05); and compared with the LPS+ATP+DMSO group, the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased contents of LDH, IL-1β, and TNF-α in the supernatant and ratio of PI +/CAM + cell counts ( P<0.05). Compared with the LPS+ATP+DMSO group (2.62±0.50), the LPS+ATP+10 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased Caspase-1 p20 protein expression (1.36±0.14, 1.32±0.07, P<0.05). Compared with the LPS+ATP+DMSO group (5.00±1.67), the LPS+ATP+5 μmol/L NSA group and LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD protein expression (1.42±0.26, 1.68±0.32, P<0.05). Compared with the LPS+ATP+DMSO group (2.28±0.24), the LPS+ATP+15 μmol/L NSA group had significantly decreased GSDMD-N protein expression (1.23±0.08, P<0.05). Conclusion:NSA can inhibit microglial pyroptosis after TBI by inhibiting the Caspase-1 p20/GSDMD pathway, thereby playing a neuroprotective role.

Objective:To investigate the variation of pharmacokinetic(PK)distribution after transfusion of coagulation fac-tor Ⅷ.(FVⅢ.)in patients with hemophilia,and to explore the clinical application of individualized rehabilita-tion training.Method:Thirteen patients diagnosed with hemophilia A were enrolled from March 2021 to May 2022.The dis-tribution characteristics of PK parameters after FVⅢ.were monitored and calculated by myPKFiT software.Indi-vidualized rehabilitation training guidance was carried out according to the individual characteristics of patients.The improvement of annual bleeding rate(ABR),annual joint bleeding rate(AJBR),Hemophilia joint health score(HJHS)and functional independence measure(FIM)score after rehabilitation training was evaluated.Result:The mean and 95%CI of clearance,steady-state distribution volume,half time were 0.03(0.02-0.03)dL/hr/kg,0.49(0.46-0.52)dL/kg,14.05(12.19-15.92)hours,respectively.The coefficients of variation(CV)of clearance,steady-state distribution volume,half time were 23.93%,10.03%and 21.97%,respective-ly.The results of the Wilcoxon signed-rank test indicated that clinical symptoms such as ABR,AJBR,HJHS and FIM were significantly improved after rehabilitation training(P<0.05).Conclusion:The distribution of pharmacokinetics of hemophilia patients shows an uneven distribution between indi-viduals,and individualized rehabilitation training can further improve the joint symptom score of hemophilia patients.

Objective:To analyze the drug-resistance pattern and molecular epidemiological characteristics of Enterobacteriales carrying the blaNDM gene in Lishui, aiming to guide clinical anti-infection treatment. Methods:Non-duplicate blaNDM-carrying Enterobacteriales, isolated from Lishui Central Hospital, were collected and identified by VITEK MS. The minimal inhibitory concentrations (MICs) were detected by the broth microdilution method. The ST types of the strains were determined by multilocus sequence typing (MLST). Plasmid types were identified by transformation or conjugation experiments and replication initiator amplification experiments. The transposon structures were detected by PCR amplification. Finally, the epidemic regularity of blaNDM gene in Lishui was analyzed from three levels: clonal group, plasmid, and mobile genetic elements. Results:A total of 109 blaNDM-positive strains were collected. Among them, 60 strains carried the blaNDM-1 gene and 49 strains carried the blaNDM-5 gene. The 109 strains showed 100% resistance to ceftazidime and cefotaxime. The resistance rates to peracillin-tazobactam and imipenem were higher than 80%. Strains carrying the blaNDM-5 gene were more resistant to meropenem than those carrying blaNDM-1 gene( P<0.05). A total of 68 STs were detected from 109 strains, and IncX3, IncFⅡγ, IncA/C and IncT/R plasmids were detected, and 90.83% of the blaNDM genes were located in the IncX3 plasmid. Twelve types of blaNDM gene surrounding structures existed, and they all carried the highly conserved blaNDM- bleMBL- trpF gene sequence. Conclusions:The blaNDM gene has diverse transmission modes in Lishui. The IncX3 plasmid is the main factor mediating its transfer, and all strains carry highly conserved blaNDM- bleMBL- trpF gene sequence.

Zishen Huoxue decoction (ZSHX) enhances cardiomyocyte viability following hypoxic stress; however, its upstream therapeutic targets remain unclear. Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway. In vitro, ZSHX inhibited pathological mitochondrial fission following hypoxic stress, regulated FUN14 domain-containing protein 1 (FUNDC1)-related mitophagy, and increased the levels of mitophagy lysosomes and microtubule-associated protein 1 light chain 3 beta II (LC3II)/translocase of outer mitochondrial membrane 20 (TOM20) expression while inhibiting the over-activated mitochondrial unfolded protein response. Additionally, ZSHX regulated the stability of beta-tubulin through Sirtuin 5 (SIRT5) and could modulate FUNDC1-related synergistic mechanisms of mitophagy and unfolded protein response in the mitochondria (UPR^mt) via the SIRT5 and -β-tubulin axis. This targeting pathway may be crucial for cardiomyocytes to resist hypoxia. Collectively, these findings suggest that ZSHX can protect against cardiomyocyte injury via the SIRT5-β-tubulin axis, which may be associated with the synergistic protective mechanism of SIRT5-β-tubulin axis-related mitophagy and UPR^mt on cardiomyocytes.
Mitophagy/drug effects* ; Tubulin/genetics* ; Animals ; Myocytes, Cardiac/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sirtuins/genetics* ; Unfolded Protein Response/drug effects* ; Myocardial Ischemia/genetics* ; Rats ; Humans ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Male

Objective To analyze the efficacy of self-formulated Bushen Qianyang Decoction combined with alendronate sodium and vitamin D3 in treating osteoporosis(OP)and to observe its effect on bone metabolism and trimethylamine oxide(TMAO)-nuclear factor κB(NF-κB)/activated T nuclear factor c1(NFATc1)pathway.Methods A total of 102 cases of patients with OP of spleen and kidney yang deficiency type who admitted to Taizhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2021 to January 2023 were randomly divided into an observation group and a western medicine group according to the random number table method,51 cases in each group.The western medicine group was treated with alendronate sodium and vitamin D,and the observation group was treated with self-formulated Bushen Qianyang Decoction on the basis of treatment for the western medicine group,and the course of treatment covered for 12 weeks.The changes of traditional Chinese medicine(TCM)syndrome score,Oswestry Disability Index(ODI)score,pain visual analogue scale(VAS)score,bone metabolism indicators,and levels of TMAO-NF-κB/NFATc1 pathway related factors before and after treatment in the two groups were observed.Moreover,the clinical efficacy and medication safety of the two groups were evaluated.Results(1)After 12 weeks of treatment,the total effective rate of the observation group was 96.08%(49/51),and that of the western medicine group was 78.43%(40/51).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the western medicine group(P<0.01).(2)After treatment,the two groups presented the decreased scores of TCM symptoms such as cold pain in the lower back,soreness and fatigue,shortness of breath and reluctance to talk,vertigo and dizziness when compared with those before treatment(P<0.05),and the decrease of TCM syndrome scores in the observation group was significantly superior to that in the western medicine group(P<0.01).(3)After treatment,the ODI scores and pain VAS scores of patients in the two groups were decreased when compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the western medicine group(P<0.01).(4)After treatment,the serum osteocalcium(BGP)level in the two groups of patients was increased when compared with that before treatment(P<0.05),and the serum total procollagen type 1 intact N(amino)-terminal propeptide(PINP)and β-collagen degradation product(β-CTX)levels were decreased when compared with those before treatment(P<0.05),and the increase of the serum BGP level and the decrease of the serum PINP and β-CTX levels in the observation group were significantly superior to those in the western medicine group(P<0.01).(5)After treatment,the levels of serum TMAO,NF-κB,and NFATc1 in the two groups of patients were all decreased when compared with those before treatment(P<0.05),and the decrease of the above indicators in the observation group was significantly superior to that in the western medicine group(P<0.01).(6)The total incidence of adverse reactions in the observation group was 5.88%(3/51)and that in the western medicine group was 9.80%(5/51),and the intergroup comparison showed that the difference was not statistically significant between the two groups(P>0.05).Conclusion Self-formulated Bushen Qianyang Decoction combined with alendronate sodium and vitamin D3 exerts certain efficacy in treating OP patients with spleen and kidney yang deficiency type,which can effectively alleviate the symptoms such as cold pain in the lower back,alleviate the degree of dysfunction,improve bone metabolism,and inhibit the high-expressed TMAO,NF-κB,and NFATc1 in the serum.Moreover,the combined therapy does not cause serious adverse reactions,with high safety.

Objective To investigate the safety and efficacy of selective hepatic inflow occlusion in laparoscopic hepatectomy.Methods A retrospective analysis was conducted on the clinical data of 64 patients who underwent laparoscopic hepatectomy.Based on the different methods of hepatic in-flow occlusion,the patients were divided into Pringle occlusion group with 31 patients(using inter-mittent Pringle's maneuver)and selective occlusion group with 33 patients(using selective hepatic inflow occlusion).The general,intraoperative,and postoperative data were compared between the two groups.Results There were no statistically significant differences in general data,operative time,intraoperative blood loss,central venous pressure,and mean arterial pressure between the two groups(P＞0.05).On postoperative day 3,the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBil)in the selective occlusion group were lower than those in the Pringle occlusion group(P＜0.05).There were no statistically significant differences in length of hospital stay and postoperative complication rates between the two groups(P＞0.05).Sub-group analysis showed that in patients undergoing laparoscopic hemihepatectomy,the AST and ALT levels on postoperative day 3 were lower in the selective occlusion group than in the Pringle occlusion group(P＜0.05).In patients undergoing laparoscopic liver segmentectomy,the TBil level on postop-erative day 3 was lower in the selective occlusion group than in the Pringle occlusion group(P＜0.05),but there were no statistically significant differences in AST and ALT levels between the two groups(P＞0.05).Conclusion Selective hepatic inflow occlusion demonstrates good safety and efficacy in laparoscopic hepatectomy.It can significantly reduce postoperative liver function damage,espe-cially in patients undergoing hemihepatectomy.