OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

OBJECTIVE: To evaluate the clinical effect and safety of acupuncture manipulation on treatment of intractable facial paralysis (IFP), and verify the practicality and precision of the Anzhong Facial Paralysis Precision Scale (Eyelid Closure Grading Scale, AFPPS-ECGS). METHODS: A multicentre, single-blind, randomized controlled trial was conducted from October 2022 to June 2024. Eighty-nine IFP participants were randomly assigned to an ordinary acupuncture group (OAG, 45 cases) and a characteristic acupuncture group (CAG, 44 cases) using a random number table method. The main acupoints selected included Yangbai (GB 14), Quanliao (SI 18), Yingxiang (LI 20), Shuigou (GV 26), Dicang (ST 4), Chengjiang (CV 24), Taiyang (EX-HN 5), Jiache (ST 6), Fengchi (GB 20), and Hegu (LI 4). The OAG patients received ordinary acupuncture manipulation, while the CAG received characteristic acupuncture manipulation. Both groups received acupuncture treatment 3 times a week, with 10 times per course, lasting for 10 weeks. Facial recovery was assessed at baseline and after the 1st, 2nd and 3rd treatment course by AFPPS-ECGS and the House-Brackmann (H-B) Grading Scale. Infrared thermography technology was used to observe the temperature difference between healthy and affected sides in various facial regions. Adverse events and laboratory test abnormalities were recorded. The correlation between the scores of the two scales was analyzed using Pearson correlation coefficient. RESULTS: After the 2nd treatment course, the two groups showed statistically significant differences in AFPPS-ECGS scores (P<0.05), with even greater significance after the 3rd course (P<0.01). Similarly, H-B Grading Scale scores demonstrated significant differences between groups following the 3rd treatment course (P<0.05). Regarding temperature measurements, significant differences in temperatures of frontal and ocular areas were observed after the 2nd course (P<0.05), becoming more pronounced after the 3rd course (P<0.01). Additionally, mouth corner temperature differences reached statistical significance by the 3rd course (P<0.05). No safety-related incidents were observed during the study. Correlation analysis revealed that the AFPPS-ECGS and the H-B Grading Scale were strongly correlated (r=0.86, 0.91, 0.93, and 0.91 at baseline, and after 1st, 2nd, and 3rd treatment course, respectively, all P<0.01). CONCLUSIONS Acupuncture is an effective treatment for IFP, and the characteristic acupuncture manipulation enhances the therapeutic effect. The use of the AFPPS-ECGS can more accurately reflect the recovery status of patients with IFP. (Trial registration No. ChiCTR2200065442).
Humans ; Acupuncture Therapy/methods* ; Facial Paralysis/therapy* ; Female ; Male ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Aged

Objective To explore the risk factors for 28-day mortality of sepsis-associated acute kidney injury(SA-AKI)patients and to develop a nomogram risk prediction model.Methods A retrospective cohort study was conducted,involving 184 patients with SA-AKI admitted to the intensive care unit(ICU)of the 940th Hospital of Joint Logistic Support Force of PLA between January 2017 and December 2022.Patients were categorized into survival(n=135)and non-survival(n=49)groups based on 28-day mortality.Clinical data were collected,and statistically significant risk factors were preliminarily screened.Multivariate stepwise logistic regression analysis was performed to identify independent risk factors for 28-day mortality of SA-AKI patients.A nomogram predictive model was constructed using these factors,and internally validated with the Bootstrap method.The receiver operating characteristic curve(ROC curve)was drawn,and the area under the ROC curve(AUC)was calculated to verify the predictive value and accuracy of the model.Results The 28-day mortality rate among 184 SA-AKI patients was 26.6％(49/184).Multivariate stepwise logistic regression analysis identified multiple organ dysfunction syndrome(MODS)(OR=16.393,95％CI 4.317-62.254,P＜0.001),high acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score(OR=1.097,95％CI 1.036-1.161,P=0.002),low oxygenation index(OR=0.992,95％CI 0.986-0.998,P=0.015),low neutrophil count(OR=0.912,95％CI 0.860-0.968,P=0.002)and low fibrinogen concentration(OR=0.733,95％CI 0.549-0.978,P=0.034)as independent risk factors.The prediction model equation was P=1/1+e-logit(P),logit(P)=-1.626+2.797×MODS+0.092×AP ACHE Ⅱ+(-0.311)×fibrinogen+(-0.092)×neutrophil count+(-0.008)×oxygenation index.Internal validation with 1000 Bootstrap resamples showed high consistency between predicted and actual values.ROC analysis showed an AUC of 0.911(95％CI 0.868-0.955,P＜0.05)for the model,with 93.9％sensitivity and 78.5％specificity at a cut-off of 0.194.The Hosmer-Lemeshow test confirmed good calibration(P=0.62),and decision-making curve analysis demonstrated clinical utility within the high-risk threshold range(0.1-0.9).Conclusions MODS,high APACHE Ⅱ score,low oxygenation index,low neutrophil count,and low fibrinogen concentration are independent risk factors for 28-day mortality in SA-AKI patients.The developed nomogram risk prediction model may provide important guidance for predicting 28-day mortality in SA-AKI patients.

Process analytical technology(PAT) is a key means for digital transformation and upgrading of the traditional Chinese medicine(TCM) manufacturing process, serving as an important guarantee for consistent and controllable TCM product quality. Near-infrared(NIR) spectroscopy has become the core technology for measuring the TCM manufacturing process. By incorporating NIR spectroscopy into PAT and starting from the construction of a smart platform for the TCM manufacturing process, this paper systematically described the development history and innovative application of the combination of NIR spectroscopy with chemometrics in measuring the TCM manufacturing process by the research team over the past two decades. Additionally, it explored the application of a validation method based on accuracy profile(AP) in the practice of NIR spectroscopy. Furthermore, the software development progress driven by NIR spectroscopy supported by modeling technology was analyzed, and the prospect of integrating NIR spectroscopy in smart factory control platforms was exemplified with the construction practices of related platforms. By integrating with the smart platform, NIR spectroscopy could improve production efficiency and guarantee product quality. Finally, the prospect of the smart platform application in measuring the TCM manufacturing process was projected. It is believed that the software development for NIR spectroscopy and the smart manufacturing platform will provide strong technical support for TCM digitalization and industrialization.
Spectroscopy, Near-Infrared/methods* ; Drugs, Chinese Herbal/analysis* ; Software ; Medicine, Chinese Traditional ; Quality Control

Objective To investigate the effects of exercise and complex environment on lipopolysaccharide(LPS)-induced dopaminergic neuron death in the substantia nigra of midbrain.Methods C57BL/6 mice were divided into control group,LPS group,LPS+swimming group and LPS+complex environment group,with 7 mice in each group.The mice in the LPS group were injected with LPS into the brain to establish an inflammatory model of Parkinson's disease and lived in cages for 2 weeks.Mice in LPS+swimming group were forced to swim for 15 minutes every day for 2 weeks after modeling.The mice in the LPS+complex environment group were placed in a complex environment for 2 weeks after modeling.The control group mice were not treated.After 14 days of modeling,behavioral experiments such as footprint,open field and rotating rod were performed on each group of mice to detect the autonomous exercise ability,exercise balance ability and depression level of mice.The expressions of tyrosine hydroxylase(TH)in substantia nigra was detected by immunohistochemical staining and Western blotting.The expressions of brain-derived neurotrophic factor(BDNF),Caspase-3,interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the substantia nigra of the midbrain were detected by Western blotting.The transcription levels of IL-1β,IL-6 and TNF-α in substantia nigra were detected by RT-PCR.Results Compared with the control group,the exercise ability and balance ability of mice in LPS group,LPS+swimming group and LPS+complex environment group decreased,the depression level increased(P＜0.001),the number of TH positive neurons and BDNF protein decreased significantly(P＜0.001),and the contents of Caspase-3,IL-1β,IL-6 and TNF-α increased significantly(P＜0.001).Compared with the LPS group,the exercise ability and balance ability of the mice in the LPS+swimming group and the LPS+complex environment group were restored,the depression level decreased significantly(P＜0.01),the survival number of TH positive neurons and the content of BDNF increased significantly(P＜0.01),Caspase-3,IL-1β,IL-6 and TNF-α reduced significantly(P＜0.01),and the phenomenon in the LPS+complex environment group was more significant.Conclusion Exercise and complex environment can inhibit LPS-induced central nervous system inflammation in mice,thereby reducing damage to midbrain substantia nigra neurons,and the inhibitory effect of LPS+complex environment group is more significant.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset, posing a serious threat to human physical and mental health. The cognitive impairments caused by AD are generally diffuse and overlap symptomatically with other neurodegenerative diseases. Moreover, the symptoms of AD are often covert, leading to missed opportunities for optimal treatment after diagnosis. Therefore, early diagnosis of AD is crucial. In vitro diagnostic biomarkers not only contribute to the early clinical diagnosis of AD but also aid in further understanding the disease's pathogenesis, predicting disease progression, and observing the effects of novel candidate therapeutic drugs in clinical trials. Currently, although there are numerous biomarkers associated with AD diagnosis, the complex nature of AD pathogenesis, limitations of individual biomarkers, and constraints of clinical detection methods have hindered the development of efficient, cost-effective, and convenient diagnostic methods and standards. This article provides an overview of the research progress on in vitro diagnostic biomarkers and detection methods related to AD in recent years.
Humans ; Alzheimer Disease/diagnosis* ; Neurodegenerative Diseases ; Early Diagnosis ; Cognitive Dysfunction ; Biomarkers

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset, posing a serious threat to human physical and mental health. The cognitive impairments caused by AD are generally diffuse and overlap symptomatically with other neurodegenerative diseases. Moreover, the symptoms of AD are often covert, leading to missed opportunities for optimal treatment after diagnosis. Therefore, early diagnosis of AD is crucial. In vitro diagnostic biomarkers not only contribute to the early clinical diagnosis of AD but also aid in further understanding the disease's pathogenesis, predicting disease progression, and observing the effects of novel candidate therapeutic drugs in clinical trials. Currently, although there are numerous biomarkers associated with AD diagnosis, the complex nature of AD pathogenesis, limitations of individual biomarkers, and constraints of clinical detection methods have hindered the development of efficient, cost-effective, and convenient diagnostic methods and standards. This article provides an overview of the research progress on in vitro diagnostic biomarkers and detection methods related to AD in recent years.
Humans ; Alzheimer Disease/diagnosis* ; Neurodegenerative Diseases ; Early Diagnosis ; Cognitive Dysfunction ; Biomarkers

Drug discrimination is a behavioral pharmacological technique to study the discriminative stimulus effects of drug. Currently drug discrimination has been widely used in preclinical drug development of CNS drugs, the most extensive of which is psychodependent research in the field of drug abuse. This review describes in general the basic principles of drug discrimination, preliminarily elaborates on the relevant characteristics and applications of the subjective effects, time-course effect, stereo specificity, individual differences, and receptor mechanisms, and its development prospects for hallucinogens and cannabis drugs are also presented.