ObjectiveTo explore the application value of probe-based confocal laser endomicroscopy (pCLE) in rapidly detecting and evaluating the morphological characteristics of digestive tract tissues in mice. MethodsTwelve male SPF Kunming mice aged 6 weeks were randomly divided into two groups. Six mice were subjected to gastric gavage with 52% Red Star Erguotou to establish the model, and six were given saline by gastric gavage as a control. After 28 days of modeling, 3 mice were randomly selected from each group. After deep anesthesia induced by inhalation of 3% isoflurane, the mice were sacrificed by cervical dislocation. The stomach, duodenum, jejunum, and rectum tissues were excised and immersed in 1% fluorescein sodium solution for staining. The microstructure of the mucosal surface of each tissue was observed using pCLE. The remaining mice in the model group and the control group were deeply anesthetized by inhaling 3% isoflurane, then cardiac perfusion was performed successively with saline and 4% paraformaldehyde. The stomach, duodenum, jejunum, and rectum tissues were excised for dehydration, section and hematoxylin-eosin (HE) staining, and the morphological changes of the tissues were observed under a microscope. ResultsUnder pCLE imaging, fluorescence staining on the surface of the gastrointestinal mucosa was uniform in the control group; the morphology of gastric pits, intestinal villi, and intestinal crypts was intact, arranged compactly, and had distinct boundaries. In the model group, the gastrointestinal mucosa exhibited mucosal swelling and deformation, with uneven fluorescence staining and fluorescein leakage. Furthermore, some tissues showed defects or cell shedding, and the boundaries between adjacent characteristic structures (e.g., gastric pits, intestinal crypts) were blurred. HE staining showed that the gastrointestinal tissue structure of the control group mice was normal and well-organized, with no structural defects. Moreover, submucosal glands were uniform in size, with no hyperplasia observed, and no obvious inflammatory cell infiltration. In the model group, some gastrointestinal mucosal structures were defective and sparsely arranged; submucosal glands showed atrophy, accompanied by obvious inflammatory cell infiltration. The histological characteristics detected by pCLE were consistent with those of HE staining. ConclusionpCLE can be used to obtain rapid, real-time, large-scale, and high-resolution microscopic imaging of the gastrointestinal mucosa, realistically and comprehensively displaying its physiological and microstructural characteristics. It shows promising prospects and practical utility in the histological evaluation of digestive system injuries in small animals.

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

ObjectiveTo explore the effect of respiratory training based on core stabilization training on lumbar disc herniation. MethodsFrom January, 2023 to October, 2024, 96 patients with lumbar disc herniation admitted to the First Affiliated Hospital of Bengbu Medical University were divided into control group (n = 32), core group (n = 32) and respiratory group (n = 32). All the groups underwent conventional rehabilitation therapy, with core stabilization training in the core group and respiratory training combined with core stabilization training in the respiratory group, additionally, for four weeks. Before and after training, the scores of Visual Analogue Scale, Japanese Orthopaedic Association (JOA) and Oswestry Dysfunction Index (ODI) were compared, the average electromyographic value (AEMG) and root mean square (RMS) value of the multifidus and transversus abdominis were detected by surface electromyography (sEMG); and the thickness of the multifidus and transversus abdominis were measured by musculoskeletal ultrasonography bilaterally. ResultsThe intra-group effect (F > 597.796, P < 0.001), inter-group effect (F > 16.535, P < 0.001) and interaction effect (F > 49.622, P < 0.001) were significant in the scores of VAS, JOA and ODI; which were better in the respiratory group than in the control group and the core group (P < 0.05), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 7971.631, P < 0.001), inter-group effect (F > 177.760, P < 0.001) and interaction effect (F > 478.771, P < 0.001) were significant in the thickness of the transversus abdominis and multifidus; which were better in the respiratory group than in the control group and the core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 144303.007, P < 0.001), inter-group effect (F > 1495.458, P < 0.001) and interaction effect (F > 3121.361, P < 0.001) were significant in the RMS of the multifidus and transversus abdominis; which were better in the respiratory group than in the control group and the core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 1890.532, P < 0.001), inter-group effect (F > 607.132, P < 0.001) and interaction effect (F > 824.923, P < 0.001) were significant in the AEMG of the multifidus and transversus abdominis; which were better in the respiratory group than in the control group and core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). ConclusionCore training combined with respiratory training can more effectively reduce pain and improve dysfunction by enhancing the strength and control of the core muscles， thus improving the quality of life of patients with lumbar disc herniation.

The general models for intermediates quality analysis in the production process of Yaobitong capsule were established by near infrared spectroscopy (NIRS) combined with chemometrics, realizing the rapid determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd and moisture. The spray-dried fine powder and total mixed granule were selected as research objects. The contents of five saponins were determined by high performance liquid chromatography and the moisture content was determined by drying method. The measured contents were used as reference values. Meanwhile, NIR spectra were collected. After removing abnormal samples by Monte Carlo cross validation (MCCV), Monte Carlo uninformative variables elimination (MC-UVE) and competitive adaptive reweighted sampling (CARS) were used to select feature variables respectively. Based on the feature variables, quantitative models were established by partial least squares regression (PLSR), extreme learning machine (ELM) and ant lion optimization least squares support vector machine (ALO-LSSVM). The results showed that CARS-ALO-LSSVM model had the optimum effect. The correlation coefficients of the six index components were greater than 0.93, and the relative standard errors were controlled within 6%. ALO-LSSVM was more suitable for a large number of samples with rich information, and the prediction effect and stability of the model were significantly improved. The general models with good predicting effect can be used for the rapid quality determination of Yaobitong capsule intermediates.

ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals ; Rats, Sprague-Dawley ; Rats ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Oxytocin/genetics* ; Receptors, Oxytocin/genetics* ; Humans ; Osteoporosis, Postmenopausal/genetics* ; Bone and Bones/drug effects* ; Brain/drug effects* ; Bone Marrow/drug effects*

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged