It has been demonstrated that long-term space flights have a significantly greater impact on the cardiovascular, skeletal, and nervous systems of astronauts. The structural and functional alterations in the skeletal and muscular systems resulting from exposure to weightlessness can lead to the development of low back pain, significantly impairing the ability of astronauts to perform tasks and respond to emergencies. Both space flight and simulated microgravity have been shown to result in low back pain among astronauts, with the following factors identified as primary contributors to this phenomenon. The occurrence of intervertebral disc (IVD) edema results in the stimulation of type IV mechanoreceptors, which subsequently activate nociceptive afferents. The protrusion of an IVD causes compression of the spinal nerve roots. Furthermore, the elongation of the vertebral column and/or the diminished lumbar curvature of the spine exert traction on the dorsal root nerves. Paravertebral muscle degeneration leads to the inhibition of decreased nociceptive activity of the wide-dynamic range neurons of the spinal dorsal horn. Moreover, endogenous pain descending facilitation triggered by conditioning stimulation can be enhanced via the thalamic mediodorsal nuclei, while endogenous pain descending inhibition triggered by conditioning stimulation can be weakened via the thalamic ventromedial nuclei. Psychological factors may contribute to the development of low back pain. The mechanisms governing the generation, maintenance, and alleviation of low back pain in weightlessness differ from those observed in normal gravitational environments. This presents a significant challenge for space medicine research. Therefore, the elucidation of the occurrence and development mechanism of low back pain in weightlessness is important for the prevention and treatment during space flight. To reduce the incidence of low back pain during long-term missions on the space station, astronauts may choose to wear specialized space clothing that can provide axial physiological loads, designed to stimulate both musculature and skeletal structures, mitigating potential increases in vertebral column length, diminished lumbar curvature, and intervertebral disc edema and/or muscular atrophy. Additionally, assuming a “fetal tuck position” described as the knees to chest position may increase lumbar IVD hydrostatic pressure, subsequently reducing disc volume, rectifying diminished lumbar curvature, and alleviating dorsal root nerve tensions. Moreover, this position may reduce type IV mechanoreceptor facilitation and nerve impulse propagation from the sinuvertebral nerves of the annulus fibrosus. Elongated posterior soft tissues (apophyseal joint capsules and ligaments) with spinal flexion may potentially stimulate type I and II mechanoreceptors. It is also recommended to exercise the paraspinal muscles to prevent and alleviate the decrease in their cross-sectional area and maintain their structure and function. Photobiomodulation has been proved to be an effective means of activating the pain descending inhibition pathway of the central nervous system. In addition, astronauts should be encouraged to participate in mission-related activities and strive to avoid psychological problems caused by the long-term confinement in a small space station. The article presents a concise review of potential causes and targeted treatment strategies for low back pain induced by space flight or simulated microgravity in recent years. Its objective is to further elucidate the mechanisms underlying the occurrence and development of low back pain in weightless environments while providing scientific evidence to inform the development of guidelines for preventing, treating, and rehabilitating low back pain during long-term space flights.

[Objective] To extract hemoglobin (Hb) from red blood cells using osmotic pressure swelling method, expected to achieve a hemoglobin dissolution rate of ≥80% and a cell membrane integrity rate of ≥70%. [Methods] Human umbilical cord blood red blood cells were used as raw materials and phosphate buffer solution was used as the swelling solution for red blood cells. A three factor three-level orthogonal experiment (n=3) was conducted to determine the optimal matching conditions for selecting the osmolality molar concentration of phosphate buffer solution, pH value of hypotonic phosphate buffer solution and volume ratio of hypotonic phosphate buffer solution to washed red blood cells. Red blood cell swelling solution samples (n=6) were prepared by the optimal matching conditions and the original process conditions. The hemoglobin dissolution rate and cell membrane integrity rate were checked. In the expanded comparative experiment, red blood cell swelling solution samples (n=6) were prepared by the optimal matching conditions and the original process conditions, which was filtered by ultrafiltration membranes. The filtration time and hemoglobin yield were checked. [Results] The optimal matching conditions for preparing red blood cell swelling solution were obtained through orthogonal experiment as follows: osmotic pressure molar concentration was 30 mOsmol/Kg, pH was 7.8, and phosphate buffer to red blood cell volume ratio was 6∶1. On the basis of the above conditions, the red blood cell swelling solution sample was compared with the original process sample: the hemoglobin dissolution rate was (82.4±1.8)% vs (78.6±3.0)% (P<0.05), and the cell membrane integrity rate was (65.8±4.0)% vs (28.7±2.3)% (P<0.05). In the expanded comparative experiment, the optimal matching conditions were compared with the original process conditions: filtration time(s) (327±9) vs (434±13) (P<0.05), and hemoglobin yield was (72.3±1.2)% vs (66.0±1.4)% (P<0.05). [Conclusion] Compared with the original preparation process, the hemoglobin extraction process which optimized through orthogonal experiments greatly reduces the cell membrane fragmentation rate and minimizes the entry of cell membrane matrix into the target solution, ensuring a slightly higher hemoglobin dissolution rate, and reducing the preparation difficulty for the subsequent cell membrane separation and further purification.

Objective To assess the risk of hearing loss caused by occupational noise exposure in workers in an automobile manufacturing plant in Tianjin, China, and to perform risk management. Methods Occupational health field investigation and noise exposure measurements were conducted from July to December 2023, and physical examination data were collected. ISO 1999:2013(E) Acoustics-Estimation of Noise-Induced Hearing Loss and WS/T 754-2016 ^“Guidelines for Risk Management of Occupational Disease Hazards Caused by Noise^” were used to predict the risk of high-frequency hearing loss and occupational noise induced deafness for operational workers and make a risk classification. Results The noise intensity of each workshop was 79.4 to 95.5 dB(A), and the maximum noise intensity of welding and stamping exceeded the standard. The results of the assessment showed that the noise level remained unchanged, and the risk of HFHL and ONID in workers increased as the predicted age and length of service increased. It was predicted that after the age of 40, the maximum risk of hearing loss in welding workers would be high risk, and the risk of stamping workers would be at higher risk, suggesting that welding and stamping were the key control posts of noise hazards in the enterprise. The N50 prediction values of permanent hearing threshold displacement caused by potential noise at all frequencies for final assembly and painting workers were lower than the measured values. Conclusion The consequences of hearing loss for workers in the welding and stamping shop noise operations at this automobile manufacturing plant are relatively serious and require risk management.

This paper comprehensively discusses on the potential neurobiological mechanisms of acupuncture in the treatment of tobacco dependence， focusing on three important aspects， including acupuncture's regulation of tobacco dependence behavior， effects of acupuncture on withdrawal syndrome， and the role of acupuncture in preventing relapse. It is found that acupuncture can inhibit drug-seeking behavior by regulating the reward pathway and related neurons， such as dopamine， thus modulating tobacco dependence behavior. It also alleviates withdrawal symptoms by improving the oral environment of smokers and reducing negative emotions after quitting. Furthermore， acupuncture can prevent relapse by decreasing brain network activity related to smoking cravings and improving cognitive brain functions like addiction memory. Currently， research on the specific neurobiological mechanism of acupuncture in treating tobacco dependence and the involved neural circuits is limited. Future research directions are proposed， including the evaluation of clinical effects， exploration of specific therapeutic mechanisms， investigation of brain pathology， and strengthening the exploration of brain functions. Additionally， combining modern technologies to clarify the neural circuits involved in acupuncture intervention will provide a basis for acupuncture treatment of tobacco addiction.

Through consulting herbal medicine， medical books， and local chronicles from past dynasties to modern times， this paper systematically researched Spatholobi Caulis from name， origin， producing areas， harvesting， processing， usage， quality evaluation， functions and indications， providing a reference for the development and utilization of famous classical formulas containing Spatholobi Caulis. According to the research， Spatholobi Caulis was first recorded in the Annals of Shunning Prefecture from the Qing dynasty. It was originally a medicinal herb commonly used in Shunning， Yunnan， and was named from the red juice resembling chicken blood that flowed out after the vein was cut off. The mainstream original plants of each dynasty were Kadsura heteroclita and Spatholobus suberectus. Among them， K. heteroclita mainly focused on dispersing blood stasis and unblocking meridians， mainly treating rheumatic pain and injuries caused by falls or blows， and it is mostly used as the raw material of Jixueteng ointments. S. suberectus was commonly used as decoction pieces in decoction， which had the functions of promoting blood circulation and replenishing blood， activating meridians and collaterals， and mainly used for treating anemia， irregular menstruation， and rheumatic bone pain. The production area of Spatholobi Caulis recorded in the Qing dynasty was Yunnan. Currently， the main production area of S. suberectus is Guangxi， while the main production area of K. interior is Yunnan. In the Qing dynasty， the usage of Spatholobi Caulis was an individual prescription with other herbs before making ointments， which was usually composed of the juice of it， safflower， angelica， and glutinous rice. But in modern times， Spatholobi Caulis is mostly sliced and dried for use. The quality of Spatholobi Caulis is often determined by the number of reddish-brown concentric circles on the cut surface， with a higher number indicating better quality. Additionally， the presence of resinous secretions is also considered desirable. Based on the research findings， it is suggested that when developing famous classical formulas containing Spatholobi Caulis， the choice of the primary source should be S. suberectus or K. heteroclita， taking into consideration the therapeutic effects of the formula. It is also recommended that the latest plant classification be referenced in the next edition of Chinese Pharmacopoeia， adjusting the primary source of Kadsurae Caulis to K. heteroclita to avoid confusion caused by inconsistent original names， and the functions adjust to promote Qi circulation and relieve pain， disperse blood stasis and unblock collaterals， treating injuries caused by falls and bruises.

Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

OBJECTIVE To investigate the effect and potential mechanism of astilbin （AST） on renal injury in chronic renal failure （CRF） rats based on the Jagged-1/Notch-1 signaling pathway. METHODS CRF model was constructed by 5/6 nephrotomy. The successfully modeled rats were randomly separated into Model group， AST low-dose group （AST-L group）， AST high-dose group （AST-H group）， high-dose of AST+Notch pathway activator （Jagged-1/FC chimerin， referred to as “JFC”） group （AST-H+ JFC group）， and control group （CK group） for open surgery without resection was set up， with 10 rats in each group. The rats in the AST-L group and AST-H group were given 40 and 80 mg/kg AST， respectively； the rats in the AST-H+JFC group were simultaneously given 80 mg/kg AST and 0.5 mg/kg JFC， and the rats in the CK group and Model group were given an equal volume of normal saline， once a day， for 4 weeks. After the last administration， the serum levels of blood urea nitrogen （BUN）， serum creatinine （SCr）， and the level of 24 h urinary protein （UP） in urine， as well as the serum levels of lactate dehydrogenase （LDH）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in each group were detected. The morphology and fibrosis of renal tissue were observed. The content of adenosine triphosphate （ATP） and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were detected. The protein expressions of transforming growth factor- β （TGF- β）， hypoxia-inducible factor-1α （HIF-1α）， α-smooth muscle actin （α-SMA）， cleaved-caspase-3， Jagged-1 and Notch-1 in renal tissue were also observed. RESULTS Compared with CK group， the renal tissue of rats in the Model group was obviously damaged， renal tissue fibrosis was severe； the serum BUN and SCr levels， urine UP level， serum 4 LDH， TNF-α and IL-6 levels， as well as the protein expressions of TGF-β， HIF-1α， α-SMA， cleaved-caspase-3， Jagged-1 and Notch-1 in renal tissue were significantly increased， while the serum IL-10 level， ATP content and activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were significantly decreased （P＜0.05）. Compared with Model group， the renal tissue damage and fibrosis in the AST groups were reduced， the serum BUN and SCr levels， urine UP level， serum LDH， TNF-α and IL-6 levels， and the protein expressions of TGF-β， HIF-1α， α-SMA， cleaved-caspase-3， Jagged-1 and Notch-1 were significantly decreased， while the serum IL-10 level， ATP content and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria were significantly increased； the changes in the aforementioned indicators in AST- H group were more significant than those in the AST-L group（P＜0.05）. JFC could significantly reverse the improvement effect of high dose of AST on renal injury in CRF rats （P＜0.05）. CONCLUSIONS AST can reduce inflammation in CRF rats， alleviate renal tissue damage and fibrosis， and improve renal mitochondrial capacity metabolism， possibly by inhibiting the Jagged-1/Notch-1 signaling pathway.

OBJECTIVE To analyze the occurrence characteristics and risk factors of adverse drug reactions （ADR） of gemcitabine for injection in national centralized volume-based procurement （hereinafter referred to as “centralized procurement”）， and provide reference for clinical safe drug use. METHODS A retrospective study was conducted to collect the relevant case reports of gemcitabine for injection reported to the National Adverse Drug Reaction Monitoring System by Inner Mongolia Autonomous Region from January 2022 to December 2023； basic information of patients， drug use status， patient outcomes， rational drug use and other information were collected， and the occurrence characteristics of ADRs with leukopenia， myelosuppression， neutropenia， thrombocytopenia and liver dysfunction were analyzed. Univariate analysis and multivariate Logistic regression were used to analyze the correlation of gender， age， combination of antitumor drugs， original malignant tumor and drug dose with ADR. RESULTS A total of 315 cases reports （315 patients） of gemcitabine-induced ADR were included in this study， with a male-to-female ratio of 1.42∶1 and age of （61.17±9.13） years. The primary malignant tumor was pancreatic cancer （73 cases， 23.17%）. Leukopenia， myelosuppression and nausea were the most common ADR， followed by neutropenia， thrombocytopenia， liver dysfunction and so on. The severity grade of ADR was mainly 1-2， and the outcome of most ADR was good. Multivariate Logistic regression analysis showed that combination of antitumor drugs was a risk factor for myelosuppression and neutropenia （RR＝2.154， 95%CI： 1.218- 3.807， P＝0.008； RR＝3.099， 95%CI： 1.240-7.744， P＝0.016）； gender （female） was a risk factor for leukopenia and liver dysfunction （RR＝0.508， 95%CI： 0.302-0.853， P＝0.010； RR＝0.301， 95%CI： 0.102-0.887， P＝0.029）. In terms of drug use rationality， there were 143 cases （45.40%） of drug 126.com use in accordance with the indications of the label， and 172 cases （54.60%） of off-label drug use. Among them， the primary malignant tumors were bladder cancer， bile duct cancer and ovarian cancer， which ranked the top three off-label drug use. CONCLUSIONS The ADR caused by gemcitabine in Inner Mongolia is mainly in the blood and digestive systems. The severity of ADRs is mainly classified as 1-2 levels， and most ADRs have good outcomes. Gender （female） and combination medication are risk factors for gemcitabine-induced ADR. Appropriate chemotherapy regimen should be selected according to the patient’s condition and physical condition， and ADR monitoring in blood and digestive systems should be strengthened during medication of gemcitabine.

ObjectiveTo investigate the effects of Shenxiong Huanglian Jiedu decoction on the clearance of amyloid β-protein （Aβ） and neuronal damage in the mouse model of Alzheimer's disease （AD）. MethodsA total of 36 SPF-grade 2-month-old C57BL/6J mice were used in this study， and the modeling was performed by bilateral hippocampal injection of Aβ oligomers in C57BL/6J mice. The experiment was conducted with a blank group， a sham operation group， a model group， low- and high-dose （3.27，6.54 g·kg^-1， respectively） Shenxiong Huanglian Jiedu decoction groups， and a positive control （donepezil hydrochloride， 0.65 mg·kg^-1） group. At the end of the drug intervention， the learning and memory abilities and the activities of mice were evaluated by the Morris water maze and open field tests. Brain histopathology was examined by hematoxylin-eosin and Nissl staining. Additionally， in vivo imaging was employed to measure the metabolism of fluorescent Aβ in the cerebrospinal fluid， and staining of ionized calcium-binding adapter molecule-1 （Iba-1） was employed to assess microglial activation in the hippocampal tissue. Additionally， neurotrophin-3 （NT-3） and brain-derived neurotrophic factor （BDNF） levels in the brain tissue and serum were determined by the immunofluorescence assay and enzyme-linked immunosorbent assay. Western blot was conducted to determine the expression of inflammation and pathway-related proteins in the hippocampal tissue. ResultsCompared with the blank group and the sham operation group， the escape latency of the mice in the model group was prolonged， the platform residence time was shortened， the hippocampal tissue showed pathological manifestations such as neuronal pyknosis， Nissl body dissolution， and microglia activation. The metabolic rate of fluorescent Aβ through cerebrospinal fluid was slowed down， and the expression levels of BDNF， NT-3， and interleukin-10 （IL-10） in the hippocampus were significantly decreased （P<0.01）. The expression levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88） and phosphorylated nuclear transcription factor-κB （p-NF-κB p65） in hippocampus were significantly increased （P<0.05， P<0.01）. Compared with the model group， the escape latency of mice in the low and high dose groups of Chinese medicine and donepezil group was shortened， and the platform residence time was prolonged. Neuronal karyopyknosis， Nissl body dissolution and microglia activation in hippocampus were improved. Fluorescence Aβ was metabolized faster by cerebrospinal fluid. The expression of BDNF and NT-3 in hippocampus was increased （P<0.01）， and the expression of TLR4， MyD88 and p-NF-κB p65 was significantly decreased （P<0.05， P<0.01）. The expression of TNF-α in the hippocampus of the high-dose group was significantly decreased （P<0.05）， and the expression of IL-10 was significantly increased （P<0.05）. The expression of TNF-α， IL-6 and IL-1β in the hippocampus of the donepezil group was significantly decreased （P<0.05， P<0.01）. ConclusionShenxiong Huanglian Jiedu decoction may mitigate neuronal damage and enhance cerebrospinal fluid flow in the mouse model of AD， thereby promoting the clearance of Aβ and improving the learning and memory abilities. These beneficial effects are likely mediated through the inhibition of microglial activation， reduction of inflammation， and modulation of the TLR4/MyD88/NF-κB signaling pathway.