LIPUS regulates the progression of knee osteoarthritis in mice through primary cilia-mediated TRPV4 channels.

Osteoarthritis (OA) is a common disease in middle-aged and elderly people. An imbalance in calcium ion homeostasis will contribute to chondrocyte apoptosis and ultimately lead to the progression of OA. Transient receptor potential channel 4 (TRPV4) is involved in the regulation of intracellular calcium homeostasis. TRPV4 is expressed in primary cilia, which can sense mechanical stimuli from outside the cell, and its abnormal expression is closely related to the development of OA. Low-intensity pulsed ultrasound (LIPUS) can alleviate chondrocyte apoptosis while the exact mechanism is unclear. In this project, with the aim of revealing the mechanism of action of LIPUS, we proposed to use OA chondrocytes and animal models, LIPUS intervention, inhibition of primary cilia, use TRPV4 inhibitors or TRPV4 agonist, and use Immunofluorescence (IF), Immunohistochemistry (IHC), Western Blot (WB), Quantitative Real-time PCR (QP) to detect the expression of cartilage synthetic matrix and endoplasmic reticulum stress markers. The results revealed that LIPUS altered primary cilia expression, promoted synthetic matrix metabolism in articular chondrocytes and was associated with primary cilia. In addition, LIPUS exerted a active effect on OA by activating TRPV4, inducing calcium inward flow, and facilitating the entry of NF-κB into the nucleus to regulate synthetic matrix gene transcription. Inhibition of TRPV4 altered primary cilia expression in response to LIPUS stimulation, and knockdown of primary cilia similarly inhibited TRPV4 function. These results suggest that LIPUS mediates TRPV4 channels through primary cilia to regulate the process of knee osteoarthritis in mice.

Understanding clinical characteristics influencing adverse outcomes of Omicron infection: a retrospective study with propensity score matching from a Fangcang hospital.

Objectives: The epidemic of coronavirus disease 2019 (COVID-19) is causing global health concerns. The aim of this study was to evaluate influence of clinical characteristics on outcomes during the Omicron outbreak. Methods: A total of 25182 hospitalized patients were enrolled, including 39 severe patients and 25143 non-severe patients. Propensity score matching (PSM) was applied to balance the baseline characteristics. Logistic regression analysis was used to assess the risk of severe disease, as well as the risk of prolonged viral shedding time (VST) and increased length of hospital stay (LOS). Results: Before PSM, patients in the severe group were older, had higher symptom scores, and had a higher proportion of comorbidities (p<0.001). After PSM, there were no significant differences in age, gender, symptom score and comorbidities between severe (n=39) and non-severe (n=156) patients. Symptoms of fever (OR=6.358, 95%CI 1.748-23.119, p=0.005) and diarrhea (OR=6.523, 95%CI 1.061-40.110, p=0.043) were independent risk factors for development of severe disease. In non-severe patients, higher symptom score was associated with prolonged VST (OR=1.056, 95% CI 1.000-1.115, p=0.049) and LOS (OR=1.128, 95% CI 1.039-1.225, p=0.004); older age was associated with longer LOS (OR=1.045, 95% CI 1.007-1.084, p=0.020). Conclusion: The overall condition of the Shanghai Omicron epidemic was relatively mild. Potential risk factors for fever, diarrhea, and higher symptom score can help clinicians to predict clinical outcomes in COVID-19 patients.

Primary Cilia: A Cellular Regulator of Articular Cartilage Degeneration.

Osteoarthritis (OA) is the most common joint disease that can cause pain and disability in adults. The main pathological characteristic of OA is cartilage degeneration, which is caused by chondrocyte apoptosis, cartilage matrix degradation, and inflammatory factor destruction. The current treatment for patients with OA focuses on delaying its progression, such as oral anti-inflammatory analgesics or injection of sodium gluconate into the joint cavity. Primary cilia are an important structure involved in cellular signal transduction. Thus, they are very sensitive to mechanical and physicochemical stimuli. It is reported that the primary cilia may play an important role in the development of OA. Here, we review the correlation between the morphology (location, length, incidence, and orientation) of chondrocyte primary cilia and OA and summarize the relevant signaling pathways in chondrocytes that could regulate the OA process through primary cilia, including Hedgehog, Wnt, and inflammation-related signaling pathways. These data provide new ideas for OA treatment.

Synthetic five-wave mixing in an integrated microcavity for visible-telecom entanglement generation.

Nonlinear optics processes lie at the heart of photonics and quantum optics for their indispensable role in light sources and information processing. During the past decades, the three- and four-wave mixing (χ(2) and χ(3)) effects have been extensively studied, especially in the micro-/nano-structures by which the photon-photon interaction strength is greatly enhanced. So far, the high-order nonlinearity beyond the χ(3) has rarely been studied in dielectric materials due to their weak intrinsic nonlinear susceptibility, even in high-quality microcavities. Here, an effective five-wave mixing process (χ(4)) is synthesized by incorporating χ(2) and χ(3) processes in a single microcavity. The coherence of the synthetic χ(4) is verified by generating time-energy entangled visible-telecom photon pairs, which requires only one drive laser at the telecom waveband. The photon-pair generation rate from the synthetic process shows an estimated enhancement factor over 500 times upon intrinsic five-wave mixing. Our work demonstrates a universal approach of nonlinear synthesis via photonic structure engineering at the mesoscopic scale rather than material engineering, and thus opens a new avenue for realizing high-order optical nonlinearities and exploring functional photonic devices.

[Clinical Trial of Electroacupuncture Treatment for Relieving Stress Responses in Patients Undergoing Gastrointestinal Surgery].

OBJECTIVE: To observe the therapeutic effect of electroacupuncture (EA) at Zusanli (ST 36) and Neiguan (PC 6) on stress responses of patients undergoing gastrointestinal surgery. METHODS: A total of 40 patients undergoing gastrointestinal surgery were randomized into conventional treatment group (control) and EA group (n＝20 in each group). Patients of the EA group received conventional treatment (pre- and post-surgical fasting, measures for gastrointestinal decompression, parenteral nutrition support, and patient controlled analgesia pump, etc.) and EA stimulation (2 Hz, 30 min) of bilateral ST 36 and PC 6 (twice after surgery, at an interval of 6 h), and patients of the control group received conventional treatment only. The visual analogue scale (VAS) score was used to assess the patients' pain severity and the blood glucose levels were detected once every 4－6 h within 24 h after operation. Serum cortisol (Cort) and adrenocorticotropic hormone (ACTH) levels were detected by chemiluminescence method, and serum D-lactic acid level (for assessing gastrointestinal mucosal injury) was assayed by ELISA. RESULTS: After the treatment, the levels of serum Cort, ACTH, D-lactate acid and the highest blood glucose were significantly lower in the EA group than those in the control group (P<0.05, P<0.01), suggesting a reduction of stress reactions after EA. But no significant difference was found between the control and EA groups in the VAS score (P>0.05). CONCLUSION: EA at ST 36 and PC 6 can alleviate stress responses and reduce intestinal mucosal damage in patients undergoing gastrointestinal surgery.

[A clinical research on renal protective effect of Xuebijing injection in patients with sepsis].

OBJECTIVE: To evaluate the protective effect of Xuebijing injection against renal injury in patients with sepsis, and to explore its possible mechanism. METHODS: A prospective randomized controlled trial (RCT) was conducted in which 62 severe patients with sepsis and septic shock admitted in Department of Critical Care Medicine of Jiangsu Province Traditional Chinese Medicine Hospital from June 2013 to December 2013 were randomly divided into control group and Xuebijing group, with 31 patients in each group. The patients in both groups received basic treatment for sepsis, and the patients in Xuebijing group were additionally given intravenous injection of Xuebijing 100 mL once a day for 7 days. In both groups, the changes in acute physiology and chronic health evaluation II (APACHE II) score were observed before treatment and 1, 3, 7 days after treatment, and the changes in the levels of interleukins (IL-6, IL-10), prothrombin time (PT), fibrinogen (Fib), activated partial thromboplastin time (APTT), serum creatinine (SCr), and Cystain C (Cys C) were determined before treatment and 1 day and 3 days after treatment. RESULTS: There was no statistically significant difference in APACHE II score before treatment between two groups, however, the APACHE II scores were significantly decreased in both groups 3 days and 7 days after treatment compared with those before treatment, and the degree of decrease in Xuebijing group was more obvious 7 days after treatment (13.61±7.62 vs. 16.34±8.70, P < 0.05). Serum concentrations of Cys C, SCr, IL-6, IL-10, PT, APTT, and Fib showed no difference between two groups before treatment (all P > 0.05), while after treatment the degrees of improvement of above indexes in Xuebijing group were obviously superior to those in control group, especially 3 days after treatment[Cys C (mg/L): 1.12±0.11 vs. 1.35±0.14, SCr (µmol/L): 115.0±31.0 vs. 135.0±24.0, IL-6 (ng/L): 54.27±28.79 vs. 73.35±31.01, PT (s): 13.50±0.11 vs. 15.71±0.11, APTT (s): 43.66±0.31 vs. 48.03±0.55, Fib (g/L): 1.91±0.51 vs. 1.51±0.52, P < 0.05 or P < 0.01]. CONCLUSIONS: Xuebijing injection has certain renal protective effect in patients with sepsis, and its mechanism is possibly related to the regulation and improvement of uncontrolled inflammatory response and coagulation function in sepsis.