ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula （扶正化积方） for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted， collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1， 2014， and December 31， 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group， while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B， there were 55 cases in the combined treatment group and 63 cases in the western medicine group； among patients with hepatitis B-related cirrhosis， there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% （3/55） in the combined treatment group and 17.46% （11/63） in the western medicine group， with a statistically significant difference between groups （Z = 2.003， P = 0.045）. Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% （9/110） in the combined treatment group and 22.58% （28/124） in the western medicine group， also showing a statistically significant difference （Z = 3.007， P = 0.003）. Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma （P＜0.05）. ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B， reducing the incidence of cirrhosis and hepatocellular carcinoma.

Objective To explore the effects and mechanisms of human umbilical cord mesenchymal stem cell (HUC-MSC)-derived exosomes (Exo) pretreated with Huangkui capsules on renal ischemia-reperfusion injury (IRI). Methods HUC-MSCs were cultured in media containing different concentrations of Huangkui capsules for 24 hours to determine cell viability and select an appropriate concentration for subsequent experiments. HUC-MSCs were pretreated with 50 μg/mL Huangkui capsules for 24 hours, and Exo were extracted using an exosome extraction kit. The morphology was observed under a transmission electron microscope, particle size was measured by nanoparticle tracking analysis, and the expression of exosomal membrane surface marker proteins was detected by Western blot. Human renal tubular epithelial cells (HK-2 cells) were randomly divided into hypoxia/reoxygenation group (M group), hypoxia/reoxygenation + Exo group (E group), and hypoxia/reoxygenation + Huangkui capsules pretreated Exo group (H group). Western blotting was used to measure the expression of endoplasmic reticulum stress (ERS)-related proteins, and real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to measure the expression of ERS-related gene messenger RNA (mRNA). Mice were randomly divided into sham operation group (Sham group), ischemia-reperfusion group (I/R group), ischemia-reperfusion + Exo group (E group), and ischemia-reperfusion + Huangkui capsules pretreated Exo group (H group). Renal histological assessment, serum creatinine (Scr), blood urea nitrogen (BUN) measurement and inflammatory factor detection were performed 24 hours later. Results Both Exo and Huangkui capsules prereated Exo had a bilayer membrane structure and a cup-shaped morphology; their average particle sizes were 116.8 nm and 81.3 nm, respectively. Both expressed CD9, CD63, TSG101. Compared with the M group, the E group had decreased relative expression of transcription factor 6 (ATF6) and protein kinase R-like endoplasmic reticulum kinase (PERK) proteins, increased mRNA relative expression, increased relative expression of C/EBP homologous protein (CHOP) protein, and decreased mRNA relative expression. Compared with the E group, the H group had decreased relative expression of ATF6, PERK, CHOP proteins, and decreased mRNA relative expression of ATF6 and PERK (all P<0.05). Animal experimental results showed that compared with the Sham group, the I/R group had increased renal tubular injury scores, Scr, BUN, interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor (TNF)-α levels. Compared with the I/R group, the E and H groups had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels. Compared with the E group, the H group had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels (all P<0.05). Conclusions Huangkui capsules pretreatment HUC-MSC-derived Exo may alleviate renal IRI by inhibiting ERS.

OBJECTIVE: To investigate correlation between preoperative C ₂ slope (C2S) and effectiveness at 2 years after short-segment anterior cervical discectomy and fusion (ACDF), with the aim of providing reliable indicators for predicting effectiveness. METHODS: One hundred and eighteen patients with cervical spondylotic myelopathy, who received short-segment ACDF between January 2018 and December 2022 and met the selection criteria, were enrolled in the study. There were 46 males and 72 females, aged from 26 to 80 years, with a mean age of 53.6 years. The operative duration was (127.6±33.46) minutes and the intraoperative blood loss was (34.75±30.40) mL. All patients were followed up 2 years. The pre- and post-operative Neck Disability Index (NDI), Japanese Orthopaedic Association (JOA) score, and visual analogue scale (VAS) score for pain were recorded. Based on the anteroposterior and lateral cervical X-ray films, the sagittal parameters of the cervical spine were measured [C ₂-C ₇ Cobb angle, C ₀-C ₂ Cobb angle, T ₁ slope, C2S, sagittal segmental angle (SSA) of the surgical segment, and average surgical disc height (ASDH) of the surgical segment]. Statistical analyses were performed to assess the differences in these indicators between pre- and post-operation, as well as the correlations between the preoperative C2S and the JOA score, NDI, and VAS score at 2 years after operation. The patients were allocated into group A (C2S >11.73°) and group B (C2S≤ 11.73°) according to the median value of the preoperative C2S (11.73°). The JOA score, NDI, and VAS score before operation and at 2 years after operation, as well as the differences between pre- and post-operative values (change values), were compared between the two groups. RESULTS: The T ₁ slope, C ₂-C ₇ Cobb angle, C ₀-C ₂ Cobb angle, SSA, and ASDH at immediate after operation and JOA score, NDI, and VAS score at 2 years after operation significantly improved in 118 patients when compared with preoperative ones ( P<0.05). Pearson correlation analysis showed that preoperative C2S was not correlated with JOA score and NDI at 2 years after operation ( P>0.05), but negatively correlated with VAS score ( P<0.05). There were 59 patients with preoperative C2S>11.73° (group A) and 59 with C2S≤11.73° (group B). There was no significant difference in preoperative JOA score, NDI, and VAS score between the two groups ( P>0.05). There were significant differences in VAS score at 2 year after operation and the change value between the two groups ( P<0.05); there was no significant difference in the JOA score and NDI ( P>0.05). CONCLUSION Patients with cervical spondylotic myelopathy and a higher preoperative C2S exhibited superior long-term pain relief and effectiveness following short-segment ACDF.
Humans ; Male ; Spinal Fusion/methods* ; Female ; Middle Aged ; Cervical Vertebrae/diagnostic imaging* ; Diskectomy/methods* ; Aged ; Adult ; Treatment Outcome ; Aged, 80 and over ; Spondylosis/diagnostic imaging* ; Pain Measurement ; Preoperative Period ; Follow-Up Studies

Endothelial dysfunction is one of the early triggers of vascular remodeling during pulmonary hypertension (PH) with complex predisposing mechanisms, mainly via an unbalanced generation of vasoactive factors, increased expression of growth factors, prothrombotic elements, and inflammatory markers. Conventional treatment regimens are restricted to a single therapeutic pathway, which usually leads to limited clinical outcomes. Combination therapies targeting multiple cells and several signaling pathways are increasingly adopted in PH treatment. Herein, inspired by the cocrystal pleomorphism theory, we prepared rod-shaped nanococrystals of the endothelin-1 (ET-1) receptor antagonist (bosentan, BST) and the anti-inflammatory drug (andrographolide, AG) for targeting the pulmonary endothelium and alleviating PH. The 525 nm-sized co-delivery system displayed a rod-like morphology, preferentially accumulated in the pulmonary endothelium and alleviated pulmonary artery (PA) remodeling. A three-week treatment with the preparation significantly alleviated the monocrotaline (MCT)- or Sugen 5416/hypoxia (SuHx)-induced PH by reducing the pulmonary artery pressure, increasing the survival rate, improving the hemodynamics, and inhibiting vascular remodeling. Mechanistically, the nanococrystals collaboratively repaired endothelial dysfunction by suppressing the pathways of ET-1/NF-κB/ICAM-1/TNF-α/IL-6. In conclusion, the cocrystal-based strategy offers a promising approach for constructing co-delivery systems. The developed rod-shaped nanococrystals effectively target the pulmonary endothelium and relieve experimental PH.

OBJECTIVES: To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice. METHODS: Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference. CONCLUSIONS CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals ; Ferroptosis/drug effects* ; Toll-Like Receptor 4/metabolism* ; Myocytes, Cardiac/metabolism* ; Mice, Inbred C57BL ; Mice ; Male ; Doxorubicin/adverse effects* ; Cinnamates/pharmacology* ; Signal Transduction ; Reactive Oxygen Species/metabolism*

The high prevalence of childhood caries poses a considerable threat to children's overall health. Traditional Chinese medicine (TCM) concepts offers a distinctive and valuable perspective on caries prevention. This study explores TCM's conceptualization of dental caries in relation to the physiological characteristics of children and proposes targeted preventive strategies, including holistic care, dietary regulation, and lifestyle modification. In addition, the study highlights the role of traditional modalities, such as Chinese herbal medicine, acupuncture, moxibustion, and tuina, in caries prevention, while emphasizing the importance of supporting children's mental health. The integration of TCM with modern medical practices holds promise for advancing research into the prevention and treatment of caries. Furthermore, promoting the overall improvement of children's health.
Dental Caries/prevention & control* ; Humans ; Medicine, Chinese Traditional ; Child ; Acupuncture Therapy ; Moxibustion ; Life Style ; Drugs, Chinese Herbal/therapeutic use*

Objective To analyze trends in the disease burden of esophageal cancer attributable to high body mass index (BMI) in the Chinese and United States populations from 1990 to 2019 and predict deaths over the next 10 years. Methods This study used Global Burden of Disease 2019 data to obtain mortality and disability-adjusted life-year (DALY) data by year, gender, and age for the disease burden of esophageal cancer attributable to high BMI in China and the United States from 1990 to 2019. Joinpoint regression analysis was conducted to analyze long-term trends. Bayesian age–period–cohort analysis was used to predict age-standardized mortality attributable to esophageal cancer in 2020–2030. Results From 1990 to 2019, the age-standardized mortality rate for esophageal cancer attributable to high BMI in China increased from 1.44/10⁵ to 1.80/10⁵ and the age-standardized DALY rate increased from 34.17/10⁵ to 40.79/10⁵. From the perspective of gender, the number of deaths, DALYs, and the corresponding age-standardized rate of males in China and the United States increased from 1990 to 2019. The age-standardized mortality and DALY rates of Chinese women showed a downward trend, decreasing by 21.36/10⁵ and 29.71/10⁵, respectively. Joinpoint analysis results revealed that the average annual percentage changes (AAPCs) in mortality attributable to esophageal cancer in the total population and men in China from 1990 to 2019 increased by 0.78% (95%CI: 0.71-0.84) and 1.52% (95%CI: 1.44-1.60), respectively, and that in females decreased by 0.88% (95%CI: −0.96-−0.80). AAPC in women in the United States rose at a slow rate of 0.07% (95%CI: 0.02-0.09). The burden of esophageal cancer deaths attributable to high BMI is predicted to continue to rise in China and the United States in 2020–2030. Conclusion The disease burden of esophageal cancer attributable to high BMI significantly increased in China from 1990 to 2019. The disease burden of esophageal cancer caused by high BMI in China is expected to increase from 2020 to 2030.

Objective:To conduct comparative analysis of lung cancer incidence and mortality, as well as long-term trends in incidence and mortality rates and risk factors in China and the United States from 1990 to 2019 based on data from the Global Burden of Disease Study 2019 (GBD 2019) .Methods:The GBD 2019 database was used to extract new lung cancer cases, deaths, and age-standardized rate data for the analysis of lung cancer incidence and deaths in China and the United States based on different sex and age groups from 1990 to 2019. Joinpoint software was used to calculate and analyze annual percentage change (APC) and average annual percentage change (AAPC) of age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of lung cancer in China and the United States from 1990 to 2019, and to analyze the long-term trends. Risk factors associated with lung cancer mortality in China and the United States were analyzed using the disability-adjusted life years (DALYs) .Results:New cases of lung cancer in China increased from 257 000 cases in 1990 to 832 900 cases in 2019, and ASIR increased from 30.20/100 000 in 1990 to 41.71/100 000 in 2019; deaths increased from 256 300 cases in 1990 to 757 200 cases in 2019, and ASMR increased from 31.18/100 000 in 1990 to 38.70/100 000 in 2019. ASIR and ASMR for lung cancer in the United States showed a decreasing trend from 1990 to 2019, with ASIR decreasing from 58.87/100 000 in 1990 to 45.13/100 000 in 2019, and ASMR decreasing from 49.35/100 000 in 1990 to 36.11/100 000 in 2019. In terms of gender, the disease burden of lung cancer in Chinese males was higher than that of females in 1990 and 2019, with new cases of lung cancer in males rising from 179 000 in 1990 to 576 200 in 2019, and ASIR rising from 44.29/100 000 in 1990 to 61.74/100 000 in 2019, mortality rising from 177 900 in 1990 to 523 200 in 2019, and ASMR rising from 46.33/100 000 in 1990 to 58.10/100 000 in 2019. The number of new cases of lung cancer in Chinese females rose from 78 100 in 1990 to 256 700 in 2019, and ASIR rose from 18.01/100 000 in 1990 to 24.76/100 000 in 2019; the number of deaths rose from 78 400 in 1990 to 234 000 in 2019, and ASMR rose from 18.63/100 000 in 1990 to 22.86/100 000 in 2019. In 2019, lung cancer incidence rates for males and females in China and the United States showed an increasing and then decreasing trend with age, with incidence rates of lung cancer in Chinese males and females peaking in the age group of 85-89 years old; and in the United States, incidence rates of lung cancer in males peaked in the age group of 85-89 years old, and incidence rates of females peaked in the age group of 80-84 years old. In 2019, it was shown that mortality rate of lung cancer among males in China increased and then decreased with age, reaching a peak in the age group of 85-89 years old, and mortality rate of lung cancer among females increased with age, reaching a peak in the age group of ≥95 years old. In the United States, lung cancer mortality rate for males and females showed an increasing and then decreasing trend with age, peaking in the 85-89 and 80-84 age groups, respectively. Incidence and mortality rates were higher for males than females in all age groups in China and the United States in 1990 and 2019. The analysis results of Joinpoint software showed that ASIR and ASMR of lung cancer in China showed an overall increasing trend from 1990 to 2019, with an AAPC of 1.16% (95% CI: 0.93%-1.38%, P<0.001) for ASIR and 0.78% (95% CI: 0.56%-1.01%, P<0.001) for ASMR, with the most obviously increasing trend in ASIR and ASMR from 1997 to 2004, the APC were 2.84% and 2.58%, respectively. Lung cancer ASIR and ASMR in the United States population showed a decreasing trend, with an AAPC of -1.08% (95% CI: -1.20%-0.96%, P<0.001) for ASIR and -1.05% (95% CI: -1.24%--0.87%, P<0.001) for ASMR. In 1990 and 2019, the major mortality-related risk factor for lung cancer in China and the United States was smoking, and the major mortality-related risk factor for lung cancer in Chinese females was environmental particulate matter pollution. Conclusion:ASIR and ASMR of lung cancer in China show an increasing trend from 1990 to 2019, and ASIR and ASMR of lung cancer in the United States show a decreasing trend. In 2019, incidence rate of lung cancer in males and females in China show an increasing and then decreasing trend with age, mortality rate of lung cancer for males show an increasing and then decreasing trend with age, and mortality rate of lung cancer for females show an increasing trend with age. Lung cancer incidence and mortality rates for males and females in the United States in 2019 show an increasing and then decreasing trend with age. In both 1990 and 2019, incidence rates and mortality rates are higher for males than for females in all age groups in both China and the United States. Smoking is the major mortality-related risk factor for lung cancer in China and the United States, and environmental particulate matter pollution is the major mortality-related risk factor for lung cancer in Chinese females.

BACKGROUND:In recent years,the development of liver organoids has made it a hot spot in the field of international liver disease research,but there is still no article on the bibliometric analysis of liver organoids. OBJECTIVE:To explore the hot trends in liver organoids in the last 20 years based on bibliometrics and visualization analysis. METHODS:We searched the articles about liver organoids in the Web of Science Core Collection from January 1,2002 to November 12,2022.Origin,Office,and CiteSpace software were used for bibliometrics and visualization analysis.We statistically analyzed the number of annually published articles,countries,institutions,authors,journals,and keywords of the articles by generating charts. RESULTS AND CONCLUSION:The number of articles,citation frequency,institutions and personnel involved in the research about liver organoids showed an overall upward trend in the last 20 years,indicating that the field was growing rapidly and attention was increasing.The USA had published the most papers and had the strongest influence in this field.Although it had invested a lot of time and energy,the number of papers published by a single research institution in the USA was not the highest among many research institutions.China was second only to the USA in the number of publications,with the Chinese Academy of Sciences and Fudan University leading the list.Utrecht University in the Netherlands was the institution with the most publications.Clevers H was the author with the highest number of articles.The article with the highest co-citation frequency was"Long-term culture of genome-stable bipotent stem cells from adult human liver".The main fields of study for liver organoids were Molecular Science,Biology,and Immunology.The most frequently occurring keywords were stem cell,in vitro,and culture.The research hotspots in the liver organoids field were mainly focused on in vitro stem cell three-dimensional culture,differentiation and gene expression.

Objective:To evaluate the effect of propofol on parvalbumin (PV) neurons in the medical prefrontal cortex(mPFC)of rats with social behavior disorders induced by chronic sleep deprivation.Methods:Forty-two SPF male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups ( n=14 each) using a random number table method: control group (group Con), chronic sleep deprivation plus natural sleep group (group CSD+ NS), and chronic sleep deprivation plus propofol group (group CSD+ Pro). Sleep deprivation model was established by the modified multiple platform method, the rats were placed in the sleep-deprivation tank for 20 h a day (14: 00-10: 00), and allowed to sleep naturally for 4 h (10: 00-14: 00) a day for 28 consecutive days. Propofol 40 mg/kg was intraperitoneally injected for 28 consecutive days after sleep deprivation in CSD+ Pro group. While the equal volume of 10% fat emulsion was given in Con and CSD+ NS groups. After the end of sleep deprivation, a three-box social experiment was used to detect the social behavior of rats, and the number of the PV positive cells and density of the perineuronal network (PNN) in the mPFC area were measured by immunofluorescence. Results:Compared with group Con, the pertentage of rapid eye movement sleep and sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly decreased, and the number of the PV positive cells and density of PNN in the mPFC area were decreased in group CSD+ NS ( P<0.05). Compared with group CSD+ NS, the sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly increased, the number of the PV positive cells and density of PNN in the mPFC area were increased( P<0.05), and no significant change was found in the percentage of the rapid eye movement sleep in group CSD+ Pro. Conclusions:Propofol probably increases the number and function of PV neurons in the mPFC and ameliorates sleep deprivation-induced social behavior disorders in sleep-deprived rats.