OBJECTIVES: To evaluate preterm white matter injury (PWMI) in neonatal rats using multimodal magnetic resonance imaging (MRI) combined with histological assessments and to explore its underlying mechanisms. METHODS: Healthy 3-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group and a PWMI group (n=12 in each group). A PWMI model was established in neonatal rats through hypoxia-ischemia. Laser speckle imaging was used to observe changes in cerebral oxygen saturation and blood flow at different time points post-modeling. Multimodal MRI was employed to assess the condition of white matter injury, while hematoxylin-eosin staining was utilized to observe morphological changes in the striatal area on the injured side. Immunofluorescence staining was performed to detect the proliferation and differentiation of oligodendrocyte precursor cells. RESULTS: At 0, 6, 12, 24, and 72 hours post-modeling, the relative blood flow and relative oxygen saturation on the injured side in the PWMI group were significantly lower than those in the sham operation group (P<0.05). At 24 hours post-modeling, T2-weighted imaging showed high signals in the white matter of the injured side in the PWMI group, with relative apparent diffusion coefficient values and Lorenz differential values being lower than those in the sham operation group (P<0.001); additionally, the arrangement of nerve cells in the PWMI group was disordered, and the number of EdU⁺PDGFR-α⁺ cells was higher than that in the sham operation group (P<0.001). At 28 days post-modeling, the relative fractional anisotropy values, the number of EdU⁺Olig2⁺ cells, and the fluorescence intensity of myelin basic protein and neurofilament protein 200 in the white matter region of the PWMI group were all lower than those in the sham operation group (P<0.001). CONCLUSIONS Multimodal MRI can evaluate early and long-term changes in PWMI in neonatal rat models in vivo, providing both imaging and pathological evidence for the diagnosis and treatment of PWMI in neonates. Hypoxia-ischemia inhibits the proliferation and differentiation of oligodendrocyte precursor cells in neonatal rats, leading to PWMI.
Animals ; Rats, Sprague-Dawley ; Magnetic Resonance Imaging/methods* ; Rats ; White Matter/injuries* ; Animals, Newborn ; Female ; Multimodal Imaging ; Male ; Hypoxia-Ischemia, Brain/pathology*

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate the effectiveness of astragalosideⅣ(AS-Ⅳ)in ameliorating radiation-induced cardiomyocyte edema and its molecular mechanism.Methods The AC 16 cells were divided into blank group,model group,AS-Ⅳ pre-irradiation administration group(Q group),post-irradiation administration group(H group)and pre-post-irradiation administration group(Q+H group).H group was incubated with 40 mol·L-1 AS-Ⅳ drug-containing medium,and the other groups were incubated with normal medium for 24 h.After 24 h of incubation,6 Gy X-ray irradiation was given to establish the cardiomyocyte edema model in all groups except the blank group,and group Q was replaced with normal medium,and group H was replaced with 40 mol·L-1 AS-Ⅳ drug-containing medium for 24 h of incubation.Calcein AM staining was used to observe the edema of AC 16 cells,Western blot method was used to detect the expression of key proteins of aqueous fluid metabolism,and Annexin-V/PI flow apoptosis assay was used to detect apoptosis of AC 16 cells.Results The area of cellular edema in blank,model,Q,H,and Q+H groups were 690.77±199.55,1 184.47±307.36,713.65±152.48,809.72±262.85 and 897.61±213.66;the relative expression levels of hypoxia inducible factor(HIF)-1α protein were 0.94±0.02,1.35±0.03,0.91±0.03,0.69±0.02 and 0.86±0.03;the relative expression levels of aquaporin 4(AQP4)protein were 0.66±0.03,1.07±0.04,0.67±0.02,0.56±0.03 and 0.56±0.02;the apoptosis rates were(3.90±0.76)％,(16.58±0.63)％,(12.91±0.51)％,(14.05±0.22)％and(12.13±0.38)％,respectively.Statistically significant differences were found between the above indicators in the blank,Q,H and Q+H groups when compared to the model group(all P＜0.05).Conclusion AS-Ⅳ can regulate water-liquid metabolism,ameliorate radiation-induced cardiomyocyte edema,and attenuate apoptosis by inhibiting the abnormal activation of the HIF-1 α/AQP4 axis in irradiated AC 16 cells.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Sialolithiasis occurs in approximately 0.45% to 1.20% of the general population. The typical clinical symptom manifests as a painful swelling of the affected glands after a meal or upon salivary stimulation, which extremely affects the life quality of the patients. With the development of sialendoscopy and lithotripsy, most sialoliths can be successfully removed with preservation of the gland. However, sialoliths in the deep hilar-parenchymal submandibular ducts and impacted parotid stones located in the proximal ducts continue to pose great challenges. Our research center for salivary gland diseases (in Peking University School and Hospital of Stomatology) has used sialendoscopy for 17 years and treated >2 000 patients with salivary gland calculi. The success rate was approximately 92% for submandibular gland calculi and 95% for parotid calculi. A variety of minimally invasive surgical techniques have been applied and developed, which add substantial improvements in the treatment of refractory sialolithiasis. Further, the radiographic positioning criteria and treatment strategy are proposed for these intractable stones. Most of the hilar-parenchymal submandibular stones are successfully removed by a transoral approach, including transoral duct slitting and intraductal basket grasping, while a small portion of superficial stones can be removed by a mini-incision in submandibular area. Impacted stones located in the distal third of parotid gland ducts are removed via "peri-ostium incision", which is applied to avoid a cicatricial stenosis from a direct ostium incision. Impacted parotid stones located in the middle and proximal third of the Stensen's duct are removed via a direct mini-incision or a peri-auricular flap. A direct transcutaneous mini-incision is commonly performed under local anesthesia with an imperceptible scar, and is indicated for most of impacted stones located in the middle third, hilum and intraglandular ducts. By contrast, a peri-auricular flap is performed under general anesthesia with relatively larger operational injury of the gland parenchyma, and should be best reserved for deeper intraglandular stones. Laser lithotripsy has been applied in the treatment of sialolithiasis in the past decade, and holmium ∶YAG laser is reported to have the best therapeutic effects. During the past 3 years, our research group has performed laser lithotripsy for a few cases with intractable salivary stones. From our experiences, withdrawal of the endoscopic tip 0.5-1.0 cm away from the extremity of the laser fiber, consistent saline irrigation, and careful monitoring of gland swelling are of vital importance for avoidance of injuries of the ductal wall and the vulnerable endoscope lens during lithotripsy. Larger calculi require multiple treatment procedures. The risk of ductal stenosis can be alleviated by endoscopic dilation. In summary, appropriate use of various endoscopy-assisted lithotomy helps preserve the gland function in most of the patients with refractory sialolithiasis. Further studies are needed in the following aspects: Transcervical removal of intraglandular submandibular stones, intraductal laser lithotripsy of impacted parotid stones and deep submandibular stones, evaluation of long-term postoperative function of the affected gland, et al.
Humans ; Salivary Gland Calculi/surgery* ; Constriction, Pathologic ; Endoscopy ; Salivary Ducts/surgery* ; Lithotripsy ; Treatment Outcome

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective: To analyze the survival time of reported HIV/AIDS and influencing factors of Yunnan Province from 1989 to 2021. Methods: The data were extracted from the Chinese HIV/AIDS comprehensive response information management system. The retrospective cohort study was conducted. The life table method was applied to calculate the survival probability. Kaplan-Meier was used to draw survival curves in different situations. Furthermore, the Cox proportion hazard regression model was constructed to identify the factors related to survival time. Results: Of the 174 510 HIV/AIDS, the all-cause mortality density was 4.23 per 100 person-years, the median survival time was 20.00 (95%CI:19.52-20.48) years, and the cumulative survival rates in 1, 10, 20, and 30 years were 90.75%, 67.50%, 47.93% and 30.85%. Multivariate Cox proportional risk regression model results showed that the risk of death among 0-14 and 15-49 years old groups were 0.44 (95%CI: 0.34-0.56) times and 0.51 (95%CI:0.50-0.52) times of ≥50 years old groups. The risk for death among the first CD4⁺T lymphocytes counts (CD4) counts levels of 200-349 cells/μl, 350-500 cells/μl and ≥501 cells/μl groups were 0.52 (95%CI: 0.50-0.53) times, 0.41 (95%CI: 0.40-0.42) times and 0.35 (95%CI: 0.34-0.36) times of 0-199 cells/μl groups. The risk of death among the cases that have not received antiretroviral therapy (ART) was 11.56 (95%CI: 11.26-11.87) times. The risk for death among the cases losing to ART, stopping to ART, both losing and stopping ART was 1.66 (95%CI:1.61-1.72) times, 2.49 (95%CI:2.39-2.60) times, and 1.65 (95%CI:1.53-1.78) times of the cases on ART. Conclusions: The influencing factors for the survival time of HIV/AIDS cases were age at diagnosis in Yunnan province from 1989 to 2021. The first CD4 counts levels, antiretroviral therapy, and ART compliance. Early diagnosis, early antiretroviral therapy, and increasing ART compliance could extend the survival time of HIV/AIDS cases.
Humans ; Middle Aged ; Retrospective Studies ; China/epidemiology* ; Acquired Immunodeficiency Syndrome/epidemiology* ; Anti-Retroviral Agents/therapeutic use* ; Asian People