This article systematically reviews the characteristics and trends of the writing, editing, publication and promotion of physiology textbooks in China from the late 19th century to the present, focusing on the introduction, development and innovation of Chinese physiology textbooks. The development of physiology textbooks in China is divided into four main stages: the introduction and initial development of physiology textbooks from the late 19th century to 1925; the localization and diversification of textbooks from 1926 to 1949, after the establishment of the Chinese Physiological Society; the exploratory phase of textbook construction after the founding of the People's Republic of China from 1949 to 1976; the formation and innovation of the textbook development process from 1977 to the present, following the restoration of the college entrance examination. For each phase, the article not only records the historical development of physiology textbooks, but also analyzes the evolution of their content, writing styles and the interaction with the social and political contexts. The article summarizes the characteristics and experiences of all these four phases. Special attention is given to the comprehensive statistical analysis of physiology textbooks published since the restoration of the college entrance examination and Economic Reform and Opening-up in 1977, revealing the changes in the number, publication trends and academic features of textbooks during this period. Finally, the article presets the future development of physiology textbooks in China, proposing that textbook writing should integrate aspects such as ideological and political education, medical humanities, basic and clinical medicine, health education, scientific research and international exchange and collaboration. The article also advocates for the application of new technologies and methods, such as artificial intelligence, virtual teaching models and knowledge graphs, to support "personalized learning". This research provides a systematic reference for the study of the history of medical education and offers theoretical support for the future innovation of physiology textbook in China.
Humans ; China ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Physiology/education* ; Textbooks as Topic/history*

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.

Objective:To evaluate the safety and efficacy of thoracic radiotherapy (TRT) for extensive-stage small cell lung cancer (ES-SCLC) patients in the era of first-line chemoimmunotherapy.Methods:Medical records of 56 patients with ES-SCLC who received thoracic radiotherapy after first-line platinum-based chemotherapy plus immunotherapy in Cancer Hospital Chinese Academy of Medical Sciences from January 2018 to December 2021 were retrospectively analyzed. The control group was not established for clinical causes. The overall survival (OS), progression-free survival (PFS) and local recurrence-free survival (LRFS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were employed to identify prognostic factors using the Cox proportional hazards model. The cumulative incidence of local regional recurrence (LRR) was estimated using the Fine-Grey competing risks regression model.Results:Among 56 patients in our cohort, 47 patients received consolidative TRT (cTRT) before progression and 9 patients received salvage TRT after progression. The median follow-up time was 21 months (95% CI=19.8-22.2 months), the median OS was not reached, the median PFS was 9 months (95% CI=7.0-13.0 months), and the 1-year and 18-month OS rates were 84.9%, 62.1%. In the cTRT group, the 1-year and 18-month OS rates were 84.1%, 64.5%, with the median PFS of 10 months; 1-year and 18-month LRFS rates were 73.6% and 66.0%, respectively; the cumulative incidence of LRR at 1-year and 2-year were 24.9% and 30.8%, respectively. No other 4-5 grade adverse events (AE) were reported except 6 patients presenting with 4 grade hematologic toxicities. Three grade radiation esophagitis occurred in 3 patients (5%). Ten patients (18%) developed 1-2 grade treatment-related pneumonitis, including 5 (9%) patients with immune related pneumonitis and 5 (9%) patients with radiation pneumonitis. Conclusion:The application of TRT after first-line chemoimmunotherapy is safe and may has potential survival benefit for patients with ES-SCLC.

Objective:To investigate the mechanism by which baicalein alleviates osteoarthritis by regulating Sirtuin (Sirt) to inhibit the senescence of fibroblast-like synoviocytes (FLS).Methods:FLS were extracted from synovium of non-osteoarthritis patients (3 patients) and osteoarthritis patients (3 patients), and assessed the senescence of FLS in osteoarthritis patients by Western blot, β-galactosidase staining and immunofluorescence, and examined the changing levels of Sirt family proteins and mRNAs in FLS. The relative expression level of Sirt1 in FLS was knocked down by transfection with Sirt1 siRNA, and the antioxidative capacity and senescence degree of FLS were analyzed. Chondrocytes were co-cultured with FLS and functional changes in chondrocytes were detected by Western blot. After inducing FLS senescence with bleomycin (BLM), different concentrations of baicalein were administered to detect the expression levels of Sirt1, p16, and p21 proteins and intracellular reactive oxygen species (ROS). The expression level of Sirt1 in FLS was knocked down, and BLM and baicalein treatments were applied. The relative expression levels of Sirt1 and ROS were detected using Western blot and ROS assays. After BLM-induced FLS senescence, baicalein and Compound C were added. The relative expression levels of phosphorylated AMP-activated protein kinase (pAMPK), nuclear factor erythroid 2-related factor 2 (NRF2), p16, p21, and ROS were detected by Western blot and ROS assays.Results:The relative expression of p16 and p21 in FLS in the osteoarthritic group were 3.66±0.38 and 3.55±0.34, which were higher than those in non-osteoarthritis group 1.00±0.07 and 1.00±0.09 ( t=11.860, P<0.001; t=12.520, P<0.001). The relative expression levels of Sirt1 and Sirt6 in FLS in the osteoarthritis group were 0.30±0.04 and 0.16±0.01, which were smaller than those in the non-osteoarthritis group 1.00 ± 0.03 and 1.00±0.04 ( t=23.840, P<0.001; t=34.130, P<0.001). After baicalein treatment, the relative expression of ROS was 2.58±0.28, 1.65±0.14 and 1.00±0.24 in the BLM, BLM+Bai and control groups, respectively, with statistically significant differences between the groups ( F=35.700, P<0.001), which was greater in the BLM and BLM+Bai than in the control group, and lower in the BLM+Bai than in the BLM group ( P<0.05). The relative expression of pAMPK and NRF2 was 0.28±0.02 and 0.38±0.09 after Compound C+Baicalein treatment, which was lower than that of 0.56±0.07 and 0.60±0.08 in the BLM+Bai group ( P<0.05). The relative expression of ROS increased from 1.75±0.16 to 3.45±0.12 ( P<0.001). The proportion of positivity in the BLM+Bai+Compound C, BLM+Bai and control groups was 47.30%±4.29%, 18.18%±3.89% and 7.70%±3.53% ( F=109.700, P<0.001), respectively, with the BLM+Bai+Compound C group being higher than that in the BLM+Bai group ( P<0.05). Conclusion:The downregulation of Sirt1 expression in patients with osteoarthritis leads to FLS senescence and accelerates the progression of osteoarthritis. Baicalein can inhibit FLS senescence by activating Sirt1/AMPK/NRF2 pathway, which may delay the progression of osteoarthritis and improve the function of chondrocytes.

OBJECTIVE: To evaluate the surgical methods for treating distal urethral stricture. METHODS: The clinical data of 80 patients with distal urethral stricture in Beijing Jishuitan Hospital, Captial Medical University between January 2018 and December 2022 were retrospectively collected. Including male genital lichen sclerosus (MGLS) 33 cases, iatrogenic injury 25 cases, postoperative hypospadias 12 cases, and other causes such as trauma 10 cases. Among these cases, strictures involved the urethral meatus in 54 instances, of which 38 were treated with meatotomy (MO), 7 with penile skin flap urethroplasty (PSFU), and 9 with oral mucosa graft urethroplasty (OMGU). There were also 26 instances where strictures involved both the navicular fossa and meatus; one case underwent PSFU while 25 underwent OMGU. Based on different surgical methods used for treatment purposes we divided the patients into MO group, PSFU group and OMGU group. The age of the three groups was (48.8±20.0) years, (53.3±21.8) years and (44.5±16.4) years. The mean±SD body mass index (BMI) was (28.6±3.9) kg/m², (29.6±3.2) kg/m² and (29.2±4.8) kg/m². The preoperative maximum flow rate was (5.8±2.3) mL/s, (6.8±2.4) mL/s and (5.7±3.1) mL/s. RESULTS: All the operations were successfully completed without Clavien Ⅲ or Ⅳ complications. The median length of strictures (measured intraoperatively) in the three groups were 1.1 (1.0, 1.6), 1.5 (1.1, 2.0) and 4.0 (2.5, 5.0) cm. The median operation time was 60.0 (60.0, 75.0), 85.0 (75.0, 112.5) and 180.0 (75.0, 330.0) min. The median estimated blood loss was 5.0 (2.0, 10.0), 15.0 (5.0, 42.5) and 180.0 (135.0, 216.3) mL. The median postoperative hospital stay was 3.5 (2.0, 5.0), 6.5 (3.5, 7.0) and 7.5 (7.0, 11.3) days. The median follow-up duration was 40.0 (26.3, 57.3), 55.0 (18.8, 62.8) and 52.5 (30.5, 64.0) months. The median postoperative maximum flow rate was 18.3 (15.5, 19.8), 19.2 (16.1, 20.1) and 17.2 (14.2, 19.6) mL/s. Among the 38 patients with MO, 33 cases had normal urination without reintervention, and 5 cases experienced recurrent strictures and required regular urethral dilation. Among the 8 patients with PSFU, 7 cases had normal urination without reintervention, and one case developed a urinary fistula, for which intervention was recommended but the patient opted to maintain the status quo. Among the 34 patients with OMGU, 28 cases had normal urination without reintervention. There were 6 instances of stenosis recurrence, with 5 cases requiring regular urethral dilations and one case requiring reconstructive surgery. The overall success rate of operation was 85.0%, and the reintervention rate was 15.0%. Statistical analysis revealed significant differences in etiologies among the three groups (P=0.002), as well as in stricture locations (P < 0.001), length of strictures (P < 0.001), operation time (P < 0.001), estimated blood loss (P < 0.001) and postoperative hospital stays (P < 0.001). However, no significant differences were observed in terms of age, BMI, history of previous urethral stricture surgeries, preoperative maximum flow rate, follow-up duration, postoperative maximum flow rate and reintervention rate. Univariate and multivariate Logistic regression analyses indicated that a history of previous urethral stricture surgeries was a risk factor for postoperative reintervention (P=0.026). CONCLUSION MO and PSFU are primarily suitable for treating short-segment (≤1.5 cm) distal penile urethral strictures, whereas OMGU is more appropriate for longer segment strictures. MO and OMGU can both be utilized in managing MGLS cases. PSFU and OMGU are more conducive to improving the appearance of the urethral meatus. The success rate of surgical management of distal penile urethral stricture is 85.0%, 15.0% of the patients still require surgical intervention after surgery, and having history of previous urethral stricture surgeries is a risk factor for postoperative reintervention.
Humans ; Urethral Stricture/surgery* ; Male ; Retrospective Studies ; Middle Aged ; Adult ; Urethra/surgery* ; Surgical Flaps ; Penis/surgery* ; Mouth Mucosa ; Urologic Surgical Procedures, Male/methods* ; Plastic Surgery Procedures/methods* ; Lichen Sclerosus et Atrophicus/surgery* ; Operative Time ; Skin Transplantation/methods* ; Aged

OBJECTIVE: Tumor-derived exosomes (TDEs) play crucial roles in intercellular communication. Hypoxia in the tumor microenvironment enhances secretion of TDEs and accelerates tumor metastasis. Jiedu recipe (JR), a traditional Chinese medicinal formula, has demonstrated efficacy in preventing the metastasis of hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unknown. METHODS: Animal experiments were performed to investigate the metastasis-preventing effects of JR. Bioinformatics analysis and in vitro assays were conducted to explore the potential targets and active components of JR. TDEs were assessed using nanoparticle tracking analysis (NTA) and Western blotting (WB). Exosomes derived from normoxic or hypoxic HCC cells (H-TDEs) were collected to establish premetastatic mouse models. JR was intragastrically administered to evaluate its metastasis-preventive effects. WB and lysosomal staining were performed to investigate the effects of JR on lysosomal function and autophagy. Bioinformatics analysis, WB, NTA, and immunofluorescence staining were used to identify the active components and potential targets of JR. RESULTS: JR effectively inhibited subcutaneous-tumor-promoted lung premetastatic niche development and tumor metastasis. It inhibited the release of exosomes from tumor cells under hypoxic condition. JR treatment promoted both lysosomal acidification and suppressed secretory autophagy, which were dysregulated in hypoxic tumor cells. Quercetin was identified as the active component in JR, and the epidermal growth factor receptor (EGFR) was identified as a potential target. Quercetin inhibited EGFR phosphorylation and promoted the nuclear translocation of transcription factor EB (TFEB). Hypoxia-impaired lysosomal function was restored, and secretory autophagy was alleviated by quercetin treatment. CONCLUSION JR suppressed HCC metastasis by inhibiting hypoxia-stimulated exosome release, restoring lysosomal function, and suppressing secretory autophagy. Quercetin acted as a key component of JR and regulated TDE release through EGFR-TFEB signaling. Our study provides a potential strategy for retarding tumor metastasis by targeting H-TDE secretion. Please cite this article as: Jia WT, Xiang S, Zhang JB, Yuan JY, Wang YQ, Liang SF, Lin WF, Zhai XF, Shang Y, Ling CQ, Cheng BB. Jiedu recipe, a compound Chinese herbal medicine, suppresses hepatocellular carcinoma metastasis by inhibiting the release of tumor-derived exosomes in a hypoxic microenvironment through the EGFR-TFEB signaling pathway. J Integr Med. 2024; 22(6): 697-709.
Exosomes/drug effects* ; Animals ; Carcinoma, Hepatocellular/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Liver Neoplasms/pathology* ; Tumor Microenvironment/drug effects* ; Mice ; Humans ; Cell Line, Tumor ; Mice, Inbred BALB C ; Neoplasm Metastasis ; Male ; Mice, Nude

Based on the concept of quality by design(QbD), the Box-Behnken design-response surface methodology combined with standard relation(SR) and analytic hierarchy process(AHP)-entropy weight method(EWM) was applied to optimize the extraction process of the classic prescription Yihuang Decoction. The content of geniposidic acid, phellodendrine hydrochloride, and berberine hydrochloride in Yihuang Decoction, the extract yield, and fingerprint similarity were used as the critical quality attributes(CQAs) of the extraction process. The extraction time, water addition, and extraction times were used as the critical process parameters(CPPs). After determining the levels of each factor and level through single-factor experiments, response surface experiments were designed according to the Box-Behnken principle, and the experimental results were analyzed. The SR between each sample and the reference sample under various evaluation indicators of different extraction parameters was calculated. The weights of the five evaluation indicators were determined using AHP-EWM, followed by comprehensive evaluation. A function model between CPPs and CQAs characterized by comprehensive scores was established to predict the optimal extraction process parameters. In the final comprehensive weight coefficients, the yield rate accounted for 43.1%, and the content of berberine hydrochloride, phellodendrine hydrochloride, and geniposidic acid accounted for 35.1%, 6.3%, and 15.5%, respectively. After comprehensive score analysis with SR, the established second-order polynomial model was statistically significant(P<0.01, and the lack of fit was not significant). The predicted optimal extraction conditions for Yihuang Decoction were determined as follows: 8-fold volume of water, extraction time of 1.5 h, and extraction once. The mean comprehensive score of the validation experiment was 85.77, with an RSD of 0.99%, and it met the quality control stan-dards for the reference sample of Yihuang Decoction. The results indicate that the optimized extraction process for Yihuang Decoction is stable and reliable, and the water extract is close in quality attributes to the reference sample. This can serve as a foundation for the research and development of granules in the future. Box-Behnken design-response surface methodology combined with SR and AHP-EWM can provide references for the modern extraction process research of other classic prescriptions.
Drugs, Chinese Herbal ; Analytic Hierarchy Process ; Berberine ; Entropy ; Water

Objective:To evaluate the efficacy and safety of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost in the treatment of brain metastases of lung cancer.Methods:Forty lung cancer patients with brain metastases who received whole-brain radiotherapy with simultaneous integrated boost and hippocampal avoidance in Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2020 were enrolled in this study. Brain MRI, survival follow-up and evaluation of side effects were performed before radiotherapy and at 1, 3, 6 and 12 months after radiotherapy, respectively. Overall survival (OS), progression-free survival (PFS) and changes in cognitive function were analyzed. Continuous data were described as Mean ± SD. Categorical data were described by frequency and composition ratio or percentage. Survival analysis was conducted by Kaplan-Meier method. Influencing factors of survival were identified by univariate and multivariate Cox's regression analyses.Results:A total of 40 patients were enrolled in the study. The median follow-up time was 14.2 months and the median OS, PFS and intracranial PFS of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis showed that male gender and newly diagnosed stage Ⅳ disease were associated with worse OS and PFS, respectively. The Hopkins verbal learning test-revised (HVLT-R) scores at baseline and 1, 3 and 6 months after radiotherapy were 21.94±2.99, 20.88±3.12, 20.03±3.14, and 19.78±2.98, respectively. The HVLT-R score at 6 months after radiotherapy was decreased by approximately 9.8% compared with the baseline. No grade 3 or above toxic and side effect occurred in the entire cohort.Conclusion:Hippocampal avoidance whole-brain irradiation with simultaneous integrated boost is a safe and effective treatment for brain metastases of lung cancer, which is expected to reduce the impact of radiotherapy on cognitive function.

Objective: To investigate the association between triiodothyronine (T₃) and inflammatory factors, and its potential effect on long-term outcomes in hospitalized patients with heart failure (HF). Methods: A total of 2 475 patients with HF admitted in Heart Failure Care Unit were consecutively enrolled in this retrospective cohort study from December 2006 to June 2018. Patients were divided into low T₃ syndrome group (n=610, 24.6%) and normal thyroid function group (n=1 865, 75.4%). The median follow-up time was 2.9 (1.0, 5.0) years. A total of 1 048 all-cause deaths were recorded at the final follow-up. The effects of free T₃ (FT₃) and high-sensitivity C-reactive protein (hsCRP) on the risk of all-cause death were evaluated by Cox regression analysis and Kaplan-Meier analysis. Results: The age of the total population was 19-95 (57±16) years, 1 823 cases (73.7%) were male. Compared to those with normal thyroid function, albumin [(36.5±5.4) vs. (40.7±4.7) g/L], hemoglobin [(129.4±25.1) vs. (140.6±20.6) g/L], total cholesterol [3.6 (3.0, 4.4) vs. 4.2 (3.5, 4.9) mmol/L] (all P<0.001) were lower, Whereas age [(60.5±16.0) vs. (55.2±15.4) years], creatinine [105.0 (83.6, 137.0) vs. 87.8 (75.6, 106.3) mmol/L], log N-terminal B-type natriuretic peptide [(8.2±1.3) vs. (7.2±1.4) ng/L] were higher in LT₃S patients (all P<0.001). In Kaplan-Meier survival analysis, patients with lower FT₃ and higher hsCRP had significantly lower cumulative survival (P<0.001), lower FT₃ combined with higher hsCRP subgroup had the highest risk of all-cause death (P_trend<0.001). In multivariate Cox regression analysis, LT₃S was an independent predictor of all-cause mortality (HR=1.40, 95%CI 1.16-1.69, P<0.001). Conclusion: LT₃S is an independent predictor of poor prognosis in patients with heart failure. FT₃ combined with hsCRP improve the predictive value of all-cause death in hospitalized patients with heart failure.
Humans ; Male ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Female ; C-Reactive Protein ; Retrospective Studies ; Heart Failure ; Prognosis ; Triiodothyronine ; Syndrome