Objective To evaluate the effectiveness,safety and economy of generic venlafaxine sustained-release capsules and the original drug in clinical practice based on real world clinical data.Methods This is a multicenter,retrospective real-world study.The information of outpatients who used venlafaxine sustained-release capsules in 7 hospitals from October 2021 to October 2022 was collected,including prescription data and laboratory data.They were divided into generic drug group and original drug group.After the baseline level was corrected by propensity score match method,the prescription daily dose,plasma concentration,medication possession ratio,the continuous medication rate for 3,6 and 9 months,dressing change rate,the incidence of adverse reactions,the frequency of drug use,the average daily cost,the annual cost per capita and the proportion of the average annual cost of drugs were compared between the two groups.Results After the baseline level was corrected by propensity score matching method,the prescription daily dose and medication possession ratio(MPR≥0.8)in the generic drug group were higher than that of the original drug group(P＜0.05).There was no statistically difference in plasma concentration between the two groups(P=0.294).The continuous medication rate for 3,6 and 9 months in the generic drug group were statistically higher than those in the original drug group(P＜0.01).The single dressing change rate of the generic drug group was lower than that of the original drug group(P=0.032).There was no significant difference in the rate of secondary dressing change between the two groups(P=1.000).There were no significant differences in the incidence of abnormal ALT,AST,TC,Na,APTT,and PLC between two groups(P＞0.05).The average daily cost of the generic drug group was lower than that of the original drug group.The per capita annual cost of drugs and the proportion of average annual cost of drugs in the generic drug group were significantly lower than those in the original drug group(P＜0.01).Conclusion In the actual clinical diagnosis and treatment,no clinically significant differences in effectiveness and safety were found between the generic venlafaxine sustained-release capsule and the original-patented,while the economic advantages of the generic drug were better than that of the original-patented drug.

Objective:To investigate the effect and safety of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) in treating the chronic pancreatitis (CP) patients with main pancreatic duct (MPD) stones and to analyze the influencing factors of success of lithotripsy.Methods:Clinical data of 132 patients with CP complicated with MPD stones treated with P-ESWL in the Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2022 to December 2023 were retrospectively analyzed, including 103 males and 29 females, aged (50.3±16.9) years. The times of P-ESWL, the success rate of stone fragmentation, the necessity of combining endoscopic retrograde cholangiopancreatograhy (ERCP), clearance rate of MPD stones, and incidence of post-P-ESWL complications (acute pancreatitis, abdominal hematoma, infection, steinstrasse, perforation, etc.) were evaluated. The factors influencing the success rate of lithotripsy were analyzed using univariate and multivariate logistic regression.Results:All patients underwent P-ESWL treatment, with (2.23±0.82) times of P-ESWL per person. The success rate of stone fragmentation was 87.1%(115/132). Of 107 CP patients (81.1%, 107/132) were treated with their first P-ESWL. Of 12 patients (9.1%, 12/132) underwent single P-ESWL, and 120 (90.9%, 120/132) underwent P-ESWL combined with ERCP. There were 95 cases (72.0%, 95/132) with effective removal of stones, and 62 (47.0%, 62/132) with complete removal of stones. Post-P-ESWL complications included eight cases (6.1%, 8/132) of acute pancreatitis, two (7.6%, 2/132) of steinstrasse complicated with acute pancreatitis and one (0.8%, 1/132) of abdominal hematoma. No infection or perforation occurred. Multivariate logistic regression analysis showed that the higher CT value of stones ( OR=1.239, 95% CI: 1.040-1.477, P=0.017) was associated with the lower success rate of stone fragmentation. Conclusion:P-ESWL is safe and effective in treating patients with CP complicated with MPD stones. The CT value of stones is a risk factor for the success rate of P-ESWL.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

OBJECTIVE: To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma. METHODS: In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously. RESULTS: In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01). CONCLUSIONS Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.
Aristolochic Acids/toxicity* ; Animals ; Humans ; NAD(P)H Dehydrogenase (Quinone)/genetics* ; HEK293 Cells ; Kidney/pathology* ; Cytochrome P-450 CYP1A2/genetics* ; Mice, Inbred C57BL ; DNA Adducts/drug effects* ; Male ; Kidney Diseases/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Prunus armeniaca ; Plant Extracts

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To investigate the effect and safety of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) in treating the chronic pancreatitis (CP) patients with main pancreatic duct (MPD) stones and to analyze the influencing factors of success of lithotripsy.Methods:Clinical data of 132 patients with CP complicated with MPD stones treated with P-ESWL in the Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2022 to December 2023 were retrospectively analyzed, including 103 males and 29 females, aged (50.3±16.9) years. The times of P-ESWL, the success rate of stone fragmentation, the necessity of combining endoscopic retrograde cholangiopancreatograhy (ERCP), clearance rate of MPD stones, and incidence of post-P-ESWL complications (acute pancreatitis, abdominal hematoma, infection, steinstrasse, perforation, etc.) were evaluated. The factors influencing the success rate of lithotripsy were analyzed using univariate and multivariate logistic regression.Results:All patients underwent P-ESWL treatment, with (2.23±0.82) times of P-ESWL per person. The success rate of stone fragmentation was 87.1%(115/132). Of 107 CP patients (81.1%, 107/132) were treated with their first P-ESWL. Of 12 patients (9.1%, 12/132) underwent single P-ESWL, and 120 (90.9%, 120/132) underwent P-ESWL combined with ERCP. There were 95 cases (72.0%, 95/132) with effective removal of stones, and 62 (47.0%, 62/132) with complete removal of stones. Post-P-ESWL complications included eight cases (6.1%, 8/132) of acute pancreatitis, two (7.6%, 2/132) of steinstrasse complicated with acute pancreatitis and one (0.8%, 1/132) of abdominal hematoma. No infection or perforation occurred. Multivariate logistic regression analysis showed that the higher CT value of stones ( OR=1.239, 95% CI: 1.040-1.477, P=0.017) was associated with the lower success rate of stone fragmentation. Conclusion:P-ESWL is safe and effective in treating patients with CP complicated with MPD stones. The CT value of stones is a risk factor for the success rate of P-ESWL.

Objective To evaluate the effectiveness,safety and economy of generic venlafaxine sustained-release capsules and the original drug in clinical practice based on real world clinical data.Methods This is a multicenter,retrospective real-world study.The information of outpatients who used venlafaxine sustained-release capsules in 7 hospitals from October 2021 to October 2022 was collected,including prescription data and laboratory data.They were divided into generic drug group and original drug group.After the baseline level was corrected by propensity score match method,the prescription daily dose,plasma concentration,medication possession ratio,the continuous medication rate for 3,6 and 9 months,dressing change rate,the incidence of adverse reactions,the frequency of drug use,the average daily cost,the annual cost per capita and the proportion of the average annual cost of drugs were compared between the two groups.Results After the baseline level was corrected by propensity score matching method,the prescription daily dose and medication possession ratio(MPR≥0.8)in the generic drug group were higher than that of the original drug group(P＜0.05).There was no statistically difference in plasma concentration between the two groups(P=0.294).The continuous medication rate for 3,6 and 9 months in the generic drug group were statistically higher than those in the original drug group(P＜0.01).The single dressing change rate of the generic drug group was lower than that of the original drug group(P=0.032).There was no significant difference in the rate of secondary dressing change between the two groups(P=1.000).There were no significant differences in the incidence of abnormal ALT,AST,TC,Na,APTT,and PLC between two groups(P＞0.05).The average daily cost of the generic drug group was lower than that of the original drug group.The per capita annual cost of drugs and the proportion of average annual cost of drugs in the generic drug group were significantly lower than those in the original drug group(P＜0.01).Conclusion In the actual clinical diagnosis and treatment,no clinically significant differences in effectiveness and safety were found between the generic venlafaxine sustained-release capsule and the original-patented,while the economic advantages of the generic drug were better than that of the original-patented drug.

Circadian rhythms are self-sustaining oscillations within biological systems that play key roles in a diverse multitude of physiological processes.The circadian clock mechanisms in brain and peripheral tissues can oscillate independently or be synchronized/disrupted by external stimuli.Dental enamel is a type of mineralized tissue that forms the exterior surface of the tooth crown.Incremental Retzius lines are readily observable microstructures of mature tooth enamel that indicate the regulation of amelogenesis by circadian rhythms.Teeth enamel is formed by enamel-forming cells known as ameloblasts,which are regulated and orchestrated by the circadian clock during amelogenesis.This review will first examine the key roles of the circadian clock in regulating ameloblasts and amelogenesis.Several physiological processes are involved,including gene expression,cell morphology,metabolic changes,matrix deposition,ion transportation,and mineralization.Next,the potential detrimental effects of circadian rhythm disruption on enamel formation are discussed.Circadian rhythm disruption can directly lead to Enamel Hypoplasia,which might also be a potential causative mechanism of amelogenesis imperfecta.Finally,future research trajectory in this field is extrapolated.It is hoped that this review will inspire more intensive research efforts and provide relevant cues in formulating novel therapeutic strategies for preventing tooth enamel developmental abnormalities.

Objective:To explore the effects and underlying mechanism of human adipose mesenchymal stem cells (ADSC)-derived exosomes on acute lung injury in septic mice.Methods:The study was an experimental study. Human ADSC of passages 4-5 were selected, and exosomes in their supernatant were isolated and extracted by differential ultracentrifugation. Exosomes were then used after identification. Twenty-four adult male BALB/c mice were selected and divided into normal control group, simple cecal ligation and puncture (CLP) group, and CLP+ADSC-exosome group according to the random number table method (the grouping method was the same below), with 8 mice in each group. The mice in simple CLP group were injected with phosphate buffer after CLP surgery (to establish an animal model of acute lung injury in septic mice), the mice in CLP+ADSC-exosome group were treated according to the corresponding group name, and the mice in normal control group were only injected with phosphate buffer. At 24 hours after surgery, the morphology of lung tissue was observed by hematoxylin-eosin staining, the apoptosis of lung tissue cells was detected by in-situ end-labeling method, the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the serum of mice was detected by enzyme-linked immunosorbent assay, the content of malondialdehyde and superoxide dismutase (SOD) in lung tissue was detected by microplate reader, and the expressions of CD86 and CD206 in mouse lung tissue cells was detected by immunofluorescence method. Mouse macrophage RAW264.7 was taken and divided into blank control group, simple lipopolysaccharide (LPS) group, and LPS+ADSC-exosome group. The cells of LPS+ADSC-exosome group and simple LPS group were cultured by adding LPS+ADSC-exosome and LPS, respectively, and cells in blank control group were routinely cultured. Twelve hours after culture, the ATP content, the percentage of mitochondrial reactive oxygen species positive cells, as well as mitochondrial membrane potential in cells were detected by related detection kits. The mRNA expression levels of M1 polarization marker inducible nitric oxide synthase (iNOS), M2 polarization marker arginase-1 (Arg1), and inflammatory factors TNF-α and IL-1β in cells were detected by real-time fluorescence quantitative reverse-transcription polymerase chain reaction method. Three samples were used for mRNA expression detection, and four samples were used for the detection of the other indicators.Results:At 24 hours after surgery, the structure of mouse lung tissues in normal control group was clear and intact without inflammatory cell infiltration. Compared with that in normal control group, the lung tissue edema as well as the infiltration of inflammatory cells of mice was much more obvious in simple CLP group. However, compared with that in simple CLP group, the lung tissue edema of mice in CLP+ADSC-exosome group was significantly alleviated, the infiltration of inflammatory cells was significantly reduced, and the cell apoptosis and necrosis were significantly improved. Twenty-four hours after surgery, compared with that in normal control group, the levels of TNF-α and IL-1β in the serum of mice in simple CLP group were significantly increased (with t values of 50.82 and 30.81, respectively, P<0.05); compared with that in simple CLP group, the levels of TNF-α and IL-1β in the serum of mice in CLP+ADSC-exosome group were significantly decreased (with t values of 16.36 and 19.25, respectively, P<0.05). Compared with that in normal control group, the content of malondialdehyde in the lung tissue of mice in simple CLP group was significantly increased ( t=9.89, P<0.05); and the content of SOD was significantly decreased ( t=5.01, P<0.05); compared with that in simple CLP group, the content of malondialdehyde in the lung tissue of mice in CLP+ADSC-exosome group was significantly decreased ( t=4.38, P<0.05), and the content of SOD was significantly increased ( t=2.97, P<0.05). Twenty-four hours after surgery, compared with that in normal control group, the proportion of CD86 positive cells in the lung tissue of mice in simple CLP group was significantly increased, and the proportion of CD206 positive cells was significantly decreased; compared with that in simple CLP group, the proportion of CD86 positive cells in the lung tissue of mice in CLP+ADSC-exosome group was significantly decreased, and the proportion of CD206 positive cells was significantly increased. After 12 hours of culture, compared with that in blank control group, the ATP content of RAW264.7 cells in simple LPS group was significantly decreased ( t=6.28, P<0.05); compared with that in simple LPS group, the ATP content of RAW264.7 cells in LPS+ADSC-exosome group was significantly increased ( t=4.01, P<0.05). After 12 hours of culture, compared with (22±4)% in blank control group, (40±6)% of positive cells of mitochondrial reactive oxygen species in RAW264.7 cells in simple LPS group was significantly increased ( t=5.04, P<0.05); compared with that in LPS group, (30±5)% of positive cells of mitochondrial reactive oxygen species in RAW264.7 cells in LPS+ADSC-exosome group was significantly decreased ( t=2.65, P<0.05). After 12 hours of culture, compared with that in blank control group, the mitochondrial membrane potential of RAW264.7 cells in simple LPS group was significantly decreased; the mitochondrial membrane potential of RAW264.7 cells in LPS+ ADSC-exosome group was between those in blank control group and simple LPS group. After 12 hours of culture, compared with that in blank control group, the mRNA expressions of TNF-α, IL-1β, and iNOS in RAW264.7 cells in simple LPS group were significantly increased (with t values of 16.51, 31.04, and 7.70, respectively, P<0.05), and the decrease in the mRNA expression of Arg1 was not statistically significant ( P>0.05); compared with that in simple LPS group, the mRNA expressions of TNF-α, IL-1β, and iNOS in RAW264.7 cells in LPS+ADSC-exosome group were significantly decreased (with t values of 11.38, 22.58, and 5.28, respectively, P<0.05), and the mRNA expression of Arg1 was significantly increased ( t=7.66, P<0.05). Conclusions:Human ADSC-exosomes may play a role in improving lung injury in septic mice by improving LPS-induced mitochondrial dysfunction in mice macrophages, inhibiting the polarization of macrophages toward M1, and reducing the inflammatory response.