Knee osteoarthritis (KOA) is a common chronic degenerative disease that not only causes pain and reduces the quality of life for patients but also imposes a significant societal burden. Clinical pathways can be developed by referencing recommendations from clinical practice guidelines to localize guidelines within the context of integrated traditional Chinese and western medical systems. However, existing clinical pathways suffer from shortcomings such as deficiencies in integrated traditional Chinese and western medical diagnosis and treatment, inadequate shared decision-making between healthcare providers and patients, and suboptimal visualization of clinical pathways. This study aimed to address and optimize the clinical pathway of KOA by comprehensively organizing and localizing the recommended guidelines. The concept of integrated traditional Chinese and western medicine was reflected through the construction of a path of joint decision-making between doctors and patients, emphasizing the coexistence of diagnosis and screening, the combination of clinical and imaging staging, joint decision-making between doctors and patients, and treatment stages. This pathway emphasizes patient-centered approach, with pain relief and functional rehabilitation running parallel, achieving the implementation of evidence-based concepts in practical medical practice. It provides a concrete basis for joint decision-making between doctors and patients in the integrated treatment of KOA with traditional Chinese and western medicine, which helps to improve diagnosis and treatment efficiency and patient quality of life.

Objective:To construct a calcium alginate (ALG-Ca 2+) composite hydrogel loaded with chlorella protein (Cp) (ALG-Ca 2+@Cp) and investigate its combined effect with microwave hyperthermia on the proliferation, apoptosis, and immune activation of mouse pancreatic cancer cells. Methods:ALG-Ca 2+@Cp was prepared using a physical cross-linking method and its physiochemical properties was characterized via scanning electron microscopy, rheological analysis, Ca 2+ release experiments, and microwave thermal conversion tests. The BCA protein quantification assay was used to evaluate the adsorption capacity of ALG-Ca 2+@Cp for pancreatic cancer cell antigens. The effects of ALG-Ca 2+@Cp extract combined with microwave intervention on pancreatic cancer cell proliferation, apoptosis protein expression, and cell viability were assessed using CCK-8 assays, ELISA, and Calcein-AM/PI double fluorescence staining. Flow cytometry was performed to determine the maturation-promoting ability of ALG-Ca 2+@Cp on immature mouse bone marrow-derived dendritic cells (BMDCs). Results:ALG-Ca 2+@Cp exhibited a three-dimensional network structure with a storage modulus (G') greater than the loss modulus (G''), demonstrating typical hydrogel properties. The hydrogel loaded with 0.5 mol/ml Ca 2+ reached 48°C after 5 minutes of microwave irradiation at 5.0 W/cm 2, and Ca 2+ release plateaued within 5 minutes. ALG-Ca 2+@Cp effectively adsorbed pancreatic cancer cell antigens. Combined with microwave treatment, it significantly reduced pancreatic cancer cell proliferation ( A450 value 0.39±0.07 vs 2.78±0.15) and increased apoptosis markers calreticulin (CRT) and high mobility group box-1 protein (HMGB1) [(557.09±37.84) pg/ml vs (135.14±11.84) pg/ml, (4.77±0.18) ng/ml vs (1.6±0.16) ng/ml], leading to decreased cell viability; and all the differences were statistically significant (all P value <0.05). ALG-Ca 2+@Cp synergistically promoted the maturation of immature BMDCs in the presence of pancreatic cancer antigens, with a CD 80+ positivity rate of (75.67±6.53)%. Conclusions:ALG-Ca 2+@Cp is successfully constructed. Its combination with microwave hyperthermia can significantly enhance the cytotoxicity and immune activation against mouse pancreatic cancer cells by targeting intracellular antigens and inducing immunogenic cell death.

Objective:To construct a calcium alginate (ALG-Ca 2+) composite hydrogel loaded with chlorella protein (Cp) (ALG-Ca 2+@Cp) and investigate its combined effect with microwave hyperthermia on the proliferation, apoptosis, and immune activation of mouse pancreatic cancer cells. Methods:ALG-Ca 2+@Cp was prepared using a physical cross-linking method and its physiochemical properties was characterized via scanning electron microscopy, rheological analysis, Ca 2+ release experiments, and microwave thermal conversion tests. The BCA protein quantification assay was used to evaluate the adsorption capacity of ALG-Ca 2+@Cp for pancreatic cancer cell antigens. The effects of ALG-Ca 2+@Cp extract combined with microwave intervention on pancreatic cancer cell proliferation, apoptosis protein expression, and cell viability were assessed using CCK-8 assays, ELISA, and Calcein-AM/PI double fluorescence staining. Flow cytometry was performed to determine the maturation-promoting ability of ALG-Ca 2+@Cp on immature mouse bone marrow-derived dendritic cells (BMDCs). Results:ALG-Ca 2+@Cp exhibited a three-dimensional network structure with a storage modulus (G') greater than the loss modulus (G''), demonstrating typical hydrogel properties. The hydrogel loaded with 0.5 mol/ml Ca 2+ reached 48°C after 5 minutes of microwave irradiation at 5.0 W/cm 2, and Ca 2+ release plateaued within 5 minutes. ALG-Ca 2+@Cp effectively adsorbed pancreatic cancer cell antigens. Combined with microwave treatment, it significantly reduced pancreatic cancer cell proliferation ( A450 value 0.39±0.07 vs 2.78±0.15) and increased apoptosis markers calreticulin (CRT) and high mobility group box-1 protein (HMGB1) [(557.09±37.84) pg/ml vs (135.14±11.84) pg/ml, (4.77±0.18) ng/ml vs (1.6±0.16) ng/ml], leading to decreased cell viability; and all the differences were statistically significant (all P value <0.05). ALG-Ca 2+@Cp synergistically promoted the maturation of immature BMDCs in the presence of pancreatic cancer antigens, with a CD 80+ positivity rate of (75.67±6.53)%. Conclusions:ALG-Ca 2+@Cp is successfully constructed. Its combination with microwave hyperthermia can significantly enhance the cytotoxicity and immune activation against mouse pancreatic cancer cells by targeting intracellular antigens and inducing immunogenic cell death.

Objective:To investigate the value of flattening filter-free (FFF) mode in postoperative deep inspiration breath-hold (DIBH) intensigy-modulated radiotherapy for left breast cancer.Methods:A retrospective case series study was conducted. Clinical data of 21 patients with left breast cancer who underwent DIBH intensity-modulated radiotherapy after modified radical surgery in Meizhou People's Hospital from January 2021 to December 2022 were retrospectively analyzed. On the DIBH-mode CT of each patient, the 7-field intensity-modulation plan was designed using the plan developed in the 6 MV FFF-mode (FFF group) or the plan developed in the 6 MV flattening filter (FF)-mode (FF group). The target areas and organs at risk, dosimetric and biological parameters, and dose validation results were compared between the two plans.Results:Twenty-one patients were female with the age [ M ( Q1, Q3)] of 47 years old (32 years old, 61 years old). The percentage of target areas receiving 95% of the prescribed dose (V 95%) was (95.9±0.8)% and (95.7±1.9)% in the FF and FFF groups ( t = 2.98, P = 0.089), and the maximum dose was (5 401±251) cGy and (5 424±201) cGy ( t = 2.85, P = 0.181), the fitness indices were 0.88±0.05 and 0.87±0.06 ( t = 0.32, P = 0.562), the homogeneity indices were 1.06±0.01 and 1.07±0.02 ( t = 2.91, P = 0.009), the equivalent uniform doses (EUD) were (51.81±0.21) Gy and (51.97±0.20) Gy ( t = 0.51, P = 0.309), and the tumor control probability (TCP) was (99.68±0.01)% and (99.61±0.02)% ( t = 0.81, P = 0.560). The plans of the FFF group and the FF group were compliant, and the doses of all organs at risk to be irradiated were within the clinically acceptable range, and the radiation doses in the FFF group in the left lung [5 Gy irradiated volume (V 5 Gy), mean dose (D mean), EUD and normal tissue complication rate (NTCP)], right lung (V 5 Gy and D mean), heart (V 10 Gy, D mean, EUD and NTCP), and right breast (V 5 Gy, D mean and EUD) were differently lower than those in the FF group, and the differences were statistically significant (all P < 0.05). The monitor units in the FFF and FF groups were (984±132) MU and (751±145) MU ( t = -1.25, P < 0.001), and the total beam-on time was (1.4±0.3) min and (2.2±0.4) min ( t = 0.68, P < 0.001); individual field beam-on time was (12±7) s and (16±10) s ( t = 2.68, P = 0.001), and the beam-on time for each field in patients of the FFF group was less than 25 s; γ pass rates were (97.1±2.8)% and (97.6±2.1)% ( t = 0.59, P = 0.484). Conclusions:In the intensity-modulated radiotherapy of left breast cancer, the radiation dose of the energy to the critical organs in FFF mode is lower and has higher dose rate and shorter treatment time. FFF combined with DIBH technique has positive clinical significance in the intensity-modulated radiotherapy of breast cancer.

Background::C-reactive protein to albumin ratio (CRP/Alb ratio, CAR) has been suggested as a potential prognostic biomarker in lung cancer. This updated systematic review and meta-analysis aimed to assess the association between CAR and lung cancer prognosis in current literature.Methods::A systematic search of databases was conducted to identify relevant studies published up to April 2023. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between CAR and overall survival (OS) and progression-free survival (PFS) and recurrence-free survival (RF) in lung cancer patients.Results::This meta-analysis includes 16 studies with a total of 5337 patients, indicating a significant association between higher CAR and poorer OS, PFS, and RFS in lung cancer patients, with a pooled HR of 1.78 (95% CI = 1.60–1.99), 1.57 (95% CI = 1.36–1.80), and 1.97 (95% CI = 1.40–2.77), respectively.Conclusions::This updated meta-analysis provides evidence for the potential prognostic role of CAR in lung cancer, suggesting its utility as an effective and noninvasive biomarker for identifying high-risk patients and informing treatment decisions in a cost-effective manner. However, further large-scale studies will be necessary to establish the optimal cut-off value for CAR in lung cancer and confirm the present findings.

Background::C-reactive protein to albumin ratio (CRP/Alb ratio, CAR) has been suggested as a potential prognostic biomarker in lung cancer. This updated systematic review and meta-analysis aimed to assess the association between CAR and lung cancer prognosis in current literature.Methods::A systematic search of databases was conducted to identify relevant studies published up to April 2023. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between CAR and overall survival (OS) and progression-free survival (PFS) and recurrence-free survival (RF) in lung cancer patients.Results::This meta-analysis includes 16 studies with a total of 5337 patients, indicating a significant association between higher CAR and poorer OS, PFS, and RFS in lung cancer patients, with a pooled HR of 1.78 (95% CI = 1.60–1.99), 1.57 (95% CI = 1.36–1.80), and 1.97 (95% CI = 1.40–2.77), respectively.Conclusions::This updated meta-analysis provides evidence for the potential prognostic role of CAR in lung cancer, suggesting its utility as an effective and noninvasive biomarker for identifying high-risk patients and informing treatment decisions in a cost-effective manner. However, further large-scale studies will be necessary to establish the optimal cut-off value for CAR in lung cancer and confirm the present findings.

Esophageal squamous cell carcinoma （ESCC）， the predominant histological strain of esophageal cancer in China， is complex in pathogenesis and may be associated with mutations in several genes and dysregulation of the mitogen-activated protein kinase （MAPK） pathway， the phosphatidylinositol 3-kinase （PI3K） pathway， etc. MAPK signaling pathway can be activated by growth factors， proto-oncogenes， and oxidative stress， thus participating in biological functions such as cell proliferation， differentiation， migration， and apoptosis. More evidence shows that the MAPK signaling pathway plays an important role in the occurrence and development of ESCC and is expected to become an effective target for the treatment of ESCC. The classical MAPK family consists of extracellular signal-regulated kinases 1/2 （ERK1/2）， c-Jun N-terminal kinases 1/2/3 （JNK1/2/3）， p38 α/β/γ/δ， and extracellular signal-regulated kinase 5 （ERK5）. Each pathway consists of three cascade sequentially phosphorylated and activated protein kinase systems. The activation of the ERK1/2 pathway is related to the proliferation， migration， drug resistance， and apoptosis inhibition of ESCC. JNK， p38， and ERK5 pathways seem to show bidirectional regulation， and there is signal integration between MAPK internal pathways. Chemotherapeutic drugs for esophageal cancer often have side effects and are prone to drug resistance， so it has become a new idea to find effective and low-toxic drug alternatives. Studies have found that flavonoids， terpenoids， alkaloids， saponins， phenols， and other active ingredients in Chinese medicine can play an anti-ESCC effect by targeting the MAPK pathway， which is mainly reflected in inhibiting proliferation， migration， and invasion， inducing cycle arrest， promoting apoptosis， reversing drug resistance， etc. Therefore， this paper reviewed the regulatory role of the MAPK signaling pathway in ESCC and the research progress in active ingredients of Chinese medicine in regulating MAPK pathway against ESCC to provide references for the mechanism research and new drug development of Chinese medicine in the prevention and treatment of esophageal cancer.

Esophageal cancer ranks the seventh and sixth in morbidity and mortality among the malignant tumors， respectively. In traditional Chinese medicine， toxic medicinals are commonly used to enhance the efficacy on esophageal cancer. In recent years， as natural drugs have become the focus of research on anti-tumor drugs， toxic Chinese medicinals have received wide attention. It has been found that a variety of toxic Chinese medicinals have significant anti-esophageal cancer effect. In this study， articles on the treatment of esophageal cancer were retrieved from SinoMed， China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP， and the toxic Chinese medicinals in the articles were summarized. It was found that the toxic Paridis Rhizoma， Gekko， Cremastrae Pseudobulbus Pleiones Pseudobulbus， Scolopendra， Hirudo， Sophorae Tonkinesis Radix et Rhizoma， Scorpio， and Bufonis Corium were mainly used for the treatment of this cancer. They can be classified into the heat-clearing and toxin-removing medicinals， toxin-counteracting medicinals， phlegm-resolving medicinals， and blood-activating and stasis-resolving medicinals. Most of them were pungent （19，52.78%） or bitter （17，47.22%）. The majority had the meridian tropism toward liver （25， 69.44%）， spleen （13， 36.11%）， and lung （12， 33.33%）. According to the research on the above commonly used toxic Chinese medicinals， most of them have anti-tumor effect and some have been reported to have anti-esophageal cancer effect. The mechanism is mainly the inhibition of proliferation. To be specific， they exert the anti-cancer effect by suppressing the proliferation， migration， and differentiation of cancer cells， inducing cell cycle arrest， and activating B-cell lymphoma/leukemia-2 （Bcl-2）-associated X protein （Bax）/Bcl-2/Caspase signaling pathway to induce apoptosis. In this paper， the commonly used toxic Chinese medicinals for the treatment of esophageal cancer were statistically analyzed， and the mechanisms were summarized， in order to provide a reference for the clinical rational use of toxic Chinese medicinals and the research on the mechanisms for their efficacy.

Objective:To investigate the factors affecting the therapeutic effects of stereotactic radiotherapy on primary liver cancer.Methods:The clinical data of 116 patients with primary liver cancer who received stereotactic radiotherapy in Binzhou Central Hospital from February 2018 to April 2020 were retrospectively analyzed. The factors that affect the therapeutic effects of stereotactic radiotherapy on primary liver cancer were analyzed.Results:Stereotactic radiotherapy was effective in 85 patients, with an overall response rate of 73.28%. There were no significant differences in maximum tumor diameter, arteriovenous fistula, portal vein tumor thrombus, distant metastasis, pseudocapsule, liver function Child-Pugh grade, Barcelona clinic liver cancer staging, and the number of stereotactic radiotherapies between different patients ( χ2 = 14.71, 12.76, 19.16, 8.54, 7.30, 7.71, 9.41, 4.08, P < 0.05 or < 0.01). Maximum tumor diameter, portal vein tumor thrombus, pseudocapsule, liver function Child-Pugh grade, Barcelona clinic liver cancer staging, and the number of stereotactic radiotherapies were the independent risk factors that affect the therapeutic effects of stereotactic radiotherapy on primary liver cancer (Wald χ2 = 3.13, 3.75, 4.16, 5.20, 3.90, 3.40, all P < 0.05). Conclusion:Many factors affect the therapeutic effects of stereotactic radiotherapy on primary liver cancer. Early identification of the high-risk factors for primary liver cancer is conducive to minimizing the risk of stereotactic radiotherapy, improving the therapeutic effects of stereotactic radiotherapy, and improving the prognosis. This study is highly innovative and scientific.

Objective:To evaluate the clinical application value of endoscopic ultrasonography (EUS) in the etiological diagnosis of patients initially diagnosed with idiopathic acute pancreatitis (IAP).Methods:Clinical data of 128 patients who underwent further EUS and magnetic resonance cholangiopancreatography (MRCP) after initial diagnosis of IAP at the Gastrointestinal Endoscopy Center of the First Affiliated Hospital of Naval Medical University between January 2015 and February 2022 were collected and divided into a single-episode group (single-episode group, 51 cases) and a multiple-episode group (recurrent group, 77 cases) based on the number of AP episodes. The data and the diagnosis of the etiology of IAP in the two groups by EUS were analyzed and compared with the etiological diagnosis results of MRCP.Results:The differences on basic information such as gender, age, history of smoking, history of alcohol consumption, family history of pancreatic disease, history of cholecystectomy, abnormality of liver function, and severity of pancreatitis between the single-episode group and recurrent group of IAP patients were not statistically significant. The etiology was clarified in 79 (62%) IAP patients after EUS examination, of which 55 (43%) cases had biliary disease (gallstones, microlithiasis, biliary sludge) and 24 (19%) cases had pancreatic disease (chronic pancreatitis, pancreatic divisum, pancreatic interstitial or pancreatic ductal changes). The percentage of patients with biliary disease as the cause of IAP was significantly higher in the single-episode group than in the recurrent group (59% vs 32%), while the percentage of patients with pancreatic disease as the cause of IAP was higher in the recurrent group than in the single-episode group (25% vs 10%), with statistically significant differences ( P values=0.004 and 0.035, respectively). The performance of EUS in diagnosing the etiology of IAP was significantly higher than that of MRCP (62% vs 19%, P=0.032), where EUS was more accurate in detecting biliary microlithiasis or biliary sludge (43% vs 9%, P<0.01). EUS was also superior to MRCP in identifying subtle changes in chronic pancreatitis lesions (small pancreatic nodules, patchy hyperechogenicity, etc.) and intraductal papillary mucinous neoplasms(17% vs 7%, P<0.05), but was inferior to MRCP in identifying pancreatic divisum (2 cases vs 4 cases). Conclusions:In view of high diagnostic accuracy and safety of EUS in diagnosing biliary diseases, and based on the fact that most IAPs in China are due to biliary diseases, EUS based management strategy can be considered to be a reasonable approach for evaluation of IAP patients. The MRCP can be used as a supplement to the EUS to identify a controversial etiology.