BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P＜0.01),the time of"stand-to-walk"decreased(P＜0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P＜0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P＞0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P＞0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P＜0.01),and the visual analog pain scale score decreased significantly(P＜0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P＜0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.

With the rapid advancement of hemodynamic indices and monitoring technologies, their classification methods and application processes have become increasingly complex. Currently, no unified standard hasbeen established, making it difficult to fully meet the clinical requirements for hemodynamic management. To assist in hemodynamic monitoring assessment and therapeutic decision-making in critically ill patients, the Critical Hemodynamic Therapy Collaborative Group, in conjunction with the Critical Ultrasound Study Group, has jointly developed the Standard for the Application of Hemodynamic Monitoring Techniques in Critical Care. The first part of this standard systematically categorizes hemodynamic indicators into flow indicators, pressure and its derivative indicators, and tissue perfusion indicators, while elaborating on the clinical application of each. The second part establishes a standardized clinical implementation pathway for hemodynamic monitoring. It proposes a tiered monitoring strategy-comprising basic, advanced, indication-specific, and special scenario monitoring-tailored to different clinical settings. It emphasizes the central role of critical care ultrasound across all levels of monitoring and establishes hemodynamic assessment standards for organs such as the brain, kidneys, and gastrointestinal tract. This standard aims to provide a unified framework for clinical practice, teaching, training, and research in critical care medicine, thereby promoting standardized development within the discipline.

ObjectiveTo establish a mouse model of particulate matter 2.5 （PM_2.5）-induced dry eye and investigate whether Chufeng Yisuntang can ameliorate the PM_2.5-induced ocular surface damage by regulating the reactive oxygen species （ROS）/p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodsSixty 8-week-old male C57BL/6J mice were used. Ten were randomly selected as the control group. The remaining 50 mice received topical instillation of 1 drop （0.1 mL） of 5 g·L^-1 PM_2.5 suspension in both eyes， four times daily. Successfully modeled mice were randomized into four groups （n=10）： Model， p38 MAPK inhibitor， Chufeng Yisuntang， and combination （Chufeng Yisuntang at 7.3 g·kg^-1 + p38 MAPK inhibitor SB203580 at 5 mg·kg^-1）. Chufeng Yisuntang was administered via gavage， and the inhibitor group via intraperitoneal injection. The control and model groups received equal volumes of distilled water by gavage. All treatments lasted for 4 weeks. General conditions were dynamically observed. Tear secretion， tear film break-up time， and corneal fluorescein staining were assessed. After intervention for 4 weeks， hematoxylin and eosin （HE） staining was used to examine the histopathological changes. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure serum levels of ROS， malondialdehyde （MDA）， superoxide dismutase （SOD） 1， and SOD2. Western blot and Real-time PCR were employed to determine the protein and gene levels， respectively， of p38 MAPK， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteinyl aspartate-specific proteinase-3 （Caspase-3） in the corneal tissue. ResultsCompared with the control group， the model group exhibited reduced tear secretion volume and tear film breakup time， along with increased corneal fluorescein staining scores （P<0.01）. Compared with the model group， the Chufeng Yisuntang group， p38 MAPK inhibitor group， and combination group demonstrated increased tear secretion volume and tear film breakup time， along with decreased corneal fluorescein staining scores （P<0.01）. HE staining revealed that compared with the control group， the model group exhibited marked increases in corneal epithelial cell layers and epithelial thickness， along with reduced meibomian gland acini and intensely stained， densely packed nuclei around the acini. Compared with the model group， the Chufeng Yisuntang group， p38 MAPK inhibitor group， and combination group showed intact corneal structure， improved cell morphology， and reduced damage severity. ELISA revealed elevated ROS and MDA levels （P<0.01） and decreased SOD1 and SOD2 levels （P<0.01） in the model group compared with the control group. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination lowered ROS and MDA levels （P<0.01）， while raising SOD1 and SOD2 levels （P<0.05， P<0.01）. Western blot revealed that compared with the control group， the model group exhibited increased protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01） and reduced protein level of Bcl-2 （P<0.01）. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination down-regulated the protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， while up-regulating the protein level of Bcl-2 （P<0.01）. Compared with the Chufeng Yisuntang group， the combination group exhibited decreased protein levels of p38 MAPK， Bax， and Caspase-3 （P<0.01） and increased protein level of Bcl-2 （P<0.01）. Real-time PCR revealed that compared with the control group， the model group exhibited upregulated mRNA levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， and downregulated mRNA level of Bcl-2 （P<0.01）. Compared with the model group， Chufeng Yisuntang， p38 MAPK inhibitor， and the combination down-regulated the mRNA levels of p38 MAPK， Bax， and Caspase-3 （P<0.01）， while up-regulating the mRNA level of Bcl-2 （P<0.05， P<0.01）. Compared with the Chufeng Yisuntang group， the combination group exhibited decreased mRNA levels of p38 MAPK， Bax， and Caspase-3 expression （P<0.05， P<0.01） and increased mRNA level of Bcl-2 （P<0.01）. ConclusionChufeng Yisuntang may partially protect against PM_2.5-induced corneal injury by inhibiting the ROS/p38 MAPK pathway， enhancing antioxidant defense， and reducing epithelial apoptosis.

BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P＜0.01),the time of"stand-to-walk"decreased(P＜0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P＜0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P＞0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P＞0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P＜0.01),and the visual analog pain scale score decreased significantly(P＜0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P＜0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.

ObjectiveTo investigate the therapeutic effects and mechanisms of modified Huangqi Jianzhong decoction （HQJZ） on gastric precancerous conditions （GPC）. MethodsIn the cell experiment， human gastric mucosal epithelial cells underwent malignant transformation induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） for the modeling of GPC （MC cells）. The cells were allocated into four groups： control ， model， low-dose HQJZ （HQJZ-L）， and high-dose HQJZ （HQJZ-H）. The control and model groups were cultured with the complete medium， while HQJZ-L and HQJZ-H groups received additional interventions with HQJZ at low （0.5 g·L^-1） and high （1.0 g·L^-1） doses， respectively. Cell counting kit-8 （CCK-8） assay was used to evaluate cytotoxicity， Transwell assay to assess cell invasion， Annexin V-FITC/PI staining to detect apoptosis， immunofluorescence assay to analyze reactive oxygen species （ROS） expression and mitochondrial autophagy， and Western blot to verify expression of proteins in key pathways. In the animal experiment， the GPC model was established in healthy BALB/c mice through MNNG induction. Twenty-four mice were allocated into four groups： control， model， HQJZ-L， and HQJZ-H. Control and model groups received normal saline （10 mL·kg^-1·d^-1） orally， while HQJZ-L and HQJZ-H groups were administrated with low-dose （6.24 g·kg^-1·d^-1） and high-dose （12.48 g·kg^-1·d^-1） HQJZ， respectively. After treatment， hematoxylin‑eosin （HE） staining and AB-PAS staining were performed to observe histopathological changes in the gastric tissue. Immunofluorescence assay was used to detect reactive oxygen species （ROS） and microtubule-associated protein 1 light chain 3 （LC3） levels in the gastric mucosa， TdT-mediated dUTP nick-end labeling （TUNEL） staining to assess apoptosis rates， and Western blotting and immunohistochemistry （IHC） to analyze the expression levels of Ki67， proliferating cell nuclear antigen （PCNA）， and foxhead box O3 （FoxO3）. ResultsCell viability assays showed that HQJZ dose-dependently reduced MC cell viability compared with the control group （P<0.05， P<0.01）. Transwell assays revealed that the model group exhibited enhanced cell invasion compared with the control group （P<0.05）. Compared with the model group， HQJZ treatment attenuated the cell invasion （P<0.05）. Gastric mucosal pathology in mice demonstrated that compared with the control group， the model group showed elevated HE and AB-PAS pathological scores （P<0.05）， while HQJZ treatment reduced these scores （P<0.05）. Transmission electron microscopy revealed increased mitochondrial number and volume in the model group compared with the control group. HQJZ treatment resulted in abnormal mitochondrial structure and significant alterations in rough endoplasmic reticulum morphology and distribution， presenting as dilated and hollow forms. Mitochondrial and apoptosis assessments indicated that compared with the control group， the model group exhibited enhanced Mito Tracker Green fluorescence （P<0.05）， no significant change in DCFH-DA fluorescence， Mito Tracker Red CMXRos fluorescence， ROS immunofluorescence， or malondialdehyde （MDA） level， increased GSH level （P<0.05）， enhanced LC3 fluorescence （P<0.05）， no significant change in apoptosis rate， and elevated ATP content in cells and mouse serum （P<0.05）. Compared with the model group， HQJZ treatment reduced Mito Tracker Green fluorescence （P<0.05）， increased DCFH-DA fluorescence， Mito Tracker Red fluorescence， MDA level， LC3 fluorescence， and apoptosis rate （P<0.05）， and decreased cellular ATP content （P<0.05）. The HQJZ-L group showed no significant change in ROS immunofluorescence or GSH level， whereas the HQJZ-H group demonstrated enhanced ROS immunofluorescence and glutathione （GSH） level （P<0.05）. Immunohistochemistry and Western blotting revealed that compared with the control group， the model group exhibited increased numbers of PCNA- and Ki67-positive cells （P<0.05） and elevated protein levels of FoxO3， sirtuin 1 （SIRT1）， and B-cell lymphoma 6 （Bcl-6） （P<0.05）. HQJZ treatment reduced the numbers of PCNA- and Ki67-positive cells （P<0.05） and lowered the protein levels of FoxO3， SIRT1， and Bcl-6 （P<0.05）. ConclusionHQJZ alleviates the progression of gastric precancerous lesions by regulating mitochondrial function via the FoxO3/ROS pathway and promoting apoptosis of GPC-malignant cells.

OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors combined with neoadjuvant chemotherapy and adjuvant chemotherapy in the treatment of early-stage triple-negative breast cancer （TNBC）. METHODS A systematic search was conducted in PubMed， Embase， Cochrane Library， CNKI， and Wanfang Data to collect randomized controlled trials （RCT） on the use of immune checkpoint inhibitors combined with neoadjuvant chemotherapy and adjuvant chemotherapy （experimental group） versus neoadjuvant chemotherapy and adjuvant chemotherapy （control group） in the treatment of TNBC. After literature screening， data extraction and literature quality evaluation， meta-analysis was performed using Stata 17.0. RESULTS A total of 5 RCT involving 1 498 patients were included. The meta-analysis results showed that the pathological complete response rate （pCR） [RR＝1.34， 95%CI （1.09， 1.63）， P＝0.03]， pCR in patients with positive programmed death-1 （PD-1） and its ligand （PD-L1） [RR＝1.33， 95%CI （1.16， 1.51）， P＝0.01]， pCR in patients with positive lymph nodes [RR＝ 1.56， 95%CI （1.27， 1.93）， P＝0.01]， the incidence of grade 3-4 adverse events （AEs） [RR＝1.07， 95%CI （1.01， 1.14）， P＝ 0.04]， the incidence of serious AEs [RR＝1.57， 95%CI （1.31， 1.87）， P＝0.03]， and the incidence of treatment discontinuation due to AEs [RR＝1.45， 95%CI （1.19， 1.76）， P＝0.01] were significantly higher in the experimental group than control group. There were no statistically significant difference in pCR in patients with negative PD-1/PD-L1[RR＝ E-mail：biejun23@126.com 1.26， 95%CI （0.98， 1.62）， P＝0.08] and pCR in patients with negative lymph nodes [RR＝1.14， 95%CI （0.97， 1.33）， P＝0.17] between the two groups. CONCLUSIONS Immune checkpoint inhibitors combined with neoadjuvant chemotherapy and adjuvant chemotherapy demonstrates significant efficacy in early-stage TNBC patients， with more pronounced benefits observed in those who are PD-1/PD-L1 positive and lymph node- positive. However， the incidence of AEs is relatively high.

OBJECTIVE To establish a content determination method for multiple components in Sophora flavescens from different origins and to evaluate its quality by combining with chemometrics. METHODS Thirteen batches （No. K1-K13） of S. flavescens from different origins were selected as test samples. A high-performance liquid chromatography-tandem triple quadrupole mass spectrometry （HPLC-MS/MS） method was established to determine the contents of 12 components， including matrine， oxymatrine， betaine， cytisine， N-methylcytisine， sophoridine， genistein， sophoricoside， sophorone， formononetin， sophorolone Ⅰ and norkurarinone in S. flavescens. Chromatographic separation was performed on a Shim-pack GIST-HP C18 column with a mobile phase consisting of methanol （A） and water containing 0.1% formic acid （B）， using gradient elution at a flow rate of 0.25 mL/min， column temperature of 35 ℃， and an injection volume of 3 μL. Mass spectrometry was conducted using an electrospray ionization source with positive and negative ion scanning. Data were collected in segments using the multiple reaction monitoring mode. Technique for order preference by similarity to ideal solution （TOPSIS） and grey relational analysis （GRA）methods were employed to compare and comprehensively evaluate the 13 batches of S. flavescens from different origins. RESULTS The methodological validation for the content determination met the relevant regulatory requirements. The contents of the 12 components were 490.66-1 231.00， 11 088.10- 18 021.50， 7.91-25.38， 903.97-1 713.64， 336.08-1 485.54，1 065.33-2 075.50， 27.52-71.80， 109.36-517.83， 6 034.55-10 632.73， 21.26-145.35， 814.84-1 911.32， 1 040.87-3 446.37 μg/g）， respectively. TOPSIS results showed that the top 7 samples in Euclidean distance ranking were K6， K12， K11， K3， K5， K10， K13. The GRA results showed that the top 7 samples in the relative correlation ranking were K12， K11， K10， K6， K13， K5， K3. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate， highly sensitive， stable and reliable. Combined with chemometrics methods， it can be used for the quality control and evaluation of S. flavescens. The comprehensive quality of samples K3， K5， K6（ from Hebei）， K10（ from Sichuan）， K11-K13（ from Shanxi）， etc. is relatively superior.

Objective: To analyze the timeliness of antir-etroviral therapy (ART) and its influencing factors among newly reported HIV/AIDS cases in Wenzhou City, Zhejiang Province from 2016 to 2023, so as to provide a reference for improving the ART effect of HIV/AIDS cases. Methods: Newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were selected as the research subjects. Demographic information, the situation of the first CD4+ T lymphocyte (CD4 cell) test, baseline CD4 cell count, and ART situation were collected through the Chinese Disease Prevention and Control Information System. The timely rate of ART was analyzed, and the influencing factors for timely ART among HIV/AIDS cases were analyzed using a multivariable logistic regression model. Results: A total of 4 500 newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were included, among which 3 679 were males, accounting for 81.76%, and 821 were females, accounting for 18.24%. The median age was 46.24 (interquartile range, 26.23) years. Among these cases, 3 606 received timely ART, with a timely rate of 80.13%. The timely rate of ART increased from 57.54% in 2016 to 91.97% in 2023 (P<0.05). Multivariable logistic regression analysis showed that unmarried/divorced/widowed (OR=0.769, 95%CI: 0.641-0.922), detainees (OR=0.492, 95%CI: 0.269-0.900), untimely first CD4 cell test (OR=0.278, 95%CI: 0.234-0.330), baseline CD4 cell count ≥200 cells/µL (OR=0.709, 95%CI: 0.595-0.843) or undetected (OR=0.131, 95%CI: 0.080-0.213) were associated with a lower timeliness for ART among HIV/AIDS cases. Conclusion From 2016 to 2023, the timely rate of ART among newly reported HIV/AIDS cases in Wenzhou City showed an upward trend, which was mainly affected by marital status, case source, timeliness of the first CD4 cell test, and baseline CD4 cell count.

ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules （SFJD） in alleviating influenza A （H1N1） virus pneumonia and focus on its effect on Toll-like receptor （TLR） signaling pathway in respiratory epithelial cells. MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 （PR8） strain of influenza A virus. Mice were randomly divided into a normal group， a PR8 infection （PR8） group， and an SFJD group （8.4 g·kg^-1）， with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg^-1 daily， while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography （Micro-CT） was performed on day 5， and the mice were dissected to collect their lungs， after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） proteins in epithelial cell adhesion molecule （EpCAM）-positive cells， and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry， and Western blot was used to detect the expression of TLR， MyD88， TRAF6， Toll-interleukin receptor domain-containing adaptor inducing interferon-β （TRIF）， inhibitor of κB kinase α （IKKα）， and nuclear factor-κB （NF-κB） in the sorted epithelial cells. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in lung tissue. ResultsAt the transcriptional level， SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells， downregulating multiple TLR signaling pathway-related genes （P<0.01）. At the protein level， SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 （P<0.05）， the expression levels of TLR2， TLR3， TLR4， TRIF， TRAF6， IKKα， and NF-κB in epithelial cells（P<0.05， P<0.01）， as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue （P<0.01）. ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.