Objective To investigate the effect and safety of Sintilimab combined with Endostar injection in the treatment of programmed cell death ligand-1(PD-L1)positive lung squamous cell carcinoma(LSCC)in elderly patients.Methods A total of 94 elderly patients with PD-L1 positive LSCC diagnosed and treated from November 2019 to November 2021 were selected as the research subjects,and they were divided into the observation group(n=47)and the control group(n=47)by random number table method.The observation group was treated with Sintilimab combined with Endostar injection,and the control group was treated with Sintilimab.Twenty-one days constituted one treatment cycle,and they were treated for 3 consecutive cycles.The clinical efficacy and improvement rate of Karnofsky performance status(KPS)score in the two groups were statistically analyzed,as well as the tumor markers[carcinoembryonic antigen(CEA),cancer antigen 125(CA125),cytokeratin 19 fragment(CYFRA21-1)],angiogenesis factors[endostatin,insulin-like growth factor-1(IGF-1),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF),and platelet-derived growth factor(PDGF)],apoptosis factor[B-cell lymphoma-2 gene(Bcl-2),Bcl-2-associated X protein(Bax),Livin protein,programmed cell death 5(PDCD5)]before and after treatment.The toxic and side effects during treatment,progression-free survival(PFS)and median survival time at 2-year follow-up were compared between the two groups.Results After treatment,the objective remission rate and disease control rate of the observation group were higher than those of the control group(P<0.01);after treatment,the improvement rate of KPS score in the observation group was higher than that in the control group(P<0.01).After treatment,the levels of serum CEA,CA125,and CYFRA21-1 in both groups decreased,and which were lower in the observation group than in the control group(P<0.05,P<0.01).After treatment,the levels of endostatin increased in both groups,while IGF-1,VEGF,bFGF,and PDGF decreased;the levels of endostatin in the observation group were higher than those in the control group,while the levels of IGF-1,VEGF,bFGF,and PDGF were lower than those in the control group(P<0.05,P<0.01).After treatment,the levels of Bcl-2 and Livin decreased in both groups,while Bax and PDCD5 increased;the levels of Bcl-2 and Livin in the observation group were lower than those in the control group,while the levels of Bax and PDCD5 were higher than those in the control group(P<0.05,P<0.01).There was no significant difference in toxic and side effects between the two groups during treatment(P>0.05).The 2-year survival rate and median survival time of the observation group were higher or longer than those of the control group(P<0.05).Conclusion The treatment of PD-L1 positive LSCC in elderly patients with Sintilimab combined with Endostar injection can improve the therapeutic effect and the survival status of patients,inhibit tumor angiogenesis,induce tumor apoptosis,prolong the survival time of patients,and has good safety.

BACKGROUND:Ankle inversion injuries frequently occur during landing,injuring the anterior talofibular and calcaneofibular ligaments.Previous studies usually used indirect indicators,such as inversion angle,as an injury risk indicator,but epidemiological support is lacking.OBJECTIVE:To calculate anterior talofibular and calcaneofibular ligament strains using a three-dimensional multi-body foot model during a drop-landing and to investigate whether increasing the foot toe-out angle for landing would reduce the risk of inversion sprains.METHODS:Thirty-five participants with high sports demands[15 males and 20 females,age:(21.0±0.9)years,height:(176.2±8.8)cm,body mass:(71.6±12.8)kg]were recruited to perform a drop-landing test using a trapdoor device to simulate ankle inversion sprains.Two landing conditions were tested,i.e.,natural landing and toe-out landing.Kinematic data were collected using a 12-camera motion analysis system,the strains of the anterior talofibular and calcaneofibular ligaments were calculated using a three-dimensional rigid-body foot model.RESULTS AND CONCLUSION:From natural landing to toe-out landing conditions,the anterior talofibular ligament strain decreased[natural landing=(3.57±1.92)％,toe-out landing=(0.36±1.18)％,P＜0.001,Cohen's d=2.01),as was the calcaneofibular ligament strain[natural landing=(1.38±1.80)％,toe-out landing=(0.28±2.29)％,P=0.003,Cohen's d=0.81).It could be concluded that increasing foot toe-out angle reduces anterior talofibular and calcaneofibular ligament strains during drop-landing with ankle inversion,thereby reducing the potential of ankle inversion sprains.

OBJECTIVE To explore the functional substance basis of Jinhong Tablet in the treatment of chronic superficial gastri-tis(CSG).METHODS Three different models were constructed to investigate the anti-inflammatory and antioxidant effects,func-tional material basis of Jinhong Tablet:inflammatory model in human gastric epithelial cells(GES-1)induced by lipopolysaccharide(LPS),LPS-induced inflammatory model in mouse gastric organoids,and ethanol-induced oxidative damage model in GES-1 cells.MTS assay was performed to detect cell proliferation activity;qPCR was applied to measure the relative mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-8(IL-8)in cells and gastric organoids;and the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and reactive oxygen species(ROS)in cells were detected.RESULTS Jinhong Tablet and 10 functional components significantly reduced the relative expression of inflammation-relat-ed genes TNF-α,IL-1β,IL-6,and IL-8 in LPS-induced GES-1 cells and gastric organoids,suggesting that these 10 components are the functional substance basis for the anti-inflammatory effects of Jin Hong Tablet.Jin Hong Tablet and 11 functional components markedly decreased the levels of MDA and ROS and increased the activity of SOD,indicating that these 11 components were the func-tional substance basis of the antioxidant effects of Jinhong Tablet.CONCLUSION Through in vitro cell and gastric organoid experi-ments,it has been preliminarily determined that allocryptopine,corydaline,dehydrocorydaline,palmatine hydrochloride,chlorogenic acid,costunolide,rutin,quercitrin,dehydrocostus lactone,tetrahydrocoptisine,isochlorogenic acid B,toosendanin,protopine,and quercetin are the functional material basis of Jinhong Tablet in treating CSG,accumulating scientific evidence for the enhancement of the quality standards of Jinhong Tablet.

BACKGROUND:With the continuous improvement of artificial biological materials and surgical techniques,total knee arthroplasty has become the preferred way to improve the quality of life of patients with knee osteoarthritis. However,patients with knee osteoarthritis have severe pain after knee arthroplasty,and there is no good treatment at present. Electroacupuncture therapy is a low-cost option for pain relief and has wide application prospects in combination with preemptive analgesia.OBJECTIVE:To investigate the effect of opposing needling acupuncture with preemptive analgesia on postoperative analgesia after initial unilateral total knee arthroplasty in patients with knee osteoarthritis.METHODS:Using a randomized controlled design,120 participants were selected from Shanghai Guanghua Hospital of Integrative Medicine. All of them received the initial unilateral total knee arthroplasty. The patients were divided into three groups by using the statistical software SPSS 25:pre-electroacupuncture group,post-electroacupuncture group,and sham group,with 40 patients in each group. In pre-electroacupuncture group,opposing needling acupuncture was performed 1 day before operation,30 minutes before anesthesia induction,and 1-3 days after operation. In post-electroacupuncture group,opposing needling acupuncture was performed with the same acupoints and parameters 1-3 days after operation,thus the sham electroacupuncture was performed 1 day before operation and 30 minutes before anesthesia induction. The sham group was treated with the same acupuncture point parameters with five times of sham electroacupuncture. The improvement of numerical rating scale after operation,the consumption of remifentanil and propofol used during operation,the time when patient first used the patient-controlled analgesia,the number of postoperative nausea and vomiting,the increase rate of thigh circumference,and the success rate of blind method were compared among the three groups.RESULTS AND CONCLUSION:(1) Compared with the pre-electroacupuncture group,the improvement of numerical rating scale at rest between post-electroacupuncture group and sham group on day 4 after operation was significantly reduced;the improvement of numerical rating scale at rest in sham group on day 7 after operation was significantly reduced (P<0.05). (2) Compared with the pre-electroacupuncture group,the improvement of numerical rating scale score between post-electroacupuncture group and sham group on day 4 after operation was significantly reduced (P<0.05),and the improvement of numerical rating scale with movement on day 7 after operation was not significant among the three groups (P>0.05). (3) Compared with the pre-electroacupuncture group,the remifentanil consumption was significantly increased in post-electroacupuncture group and sham group (P<0.05). (4) Compared with the pre-electroacupuncture group,the first time used the patient-controlled analgesia pump was significantly shortened in post-electroacupuncture group and sham group (P<0.05). (5) Compared with the pre-electroacupuncture group,the number of postoperative nausea was increased in post-electroacupuncture group and sham group (P<0.05). (6) Compared with the pre-electroacupuncture group,the increase rate of thigh circumference in post-electroacupuncture group and sham group was significantly increased on day 3 and day 7 after operation (P<0.05). Compared with the post-electroacupuncture group,the increase rate of thigh circumference in sham group was significantly increased on day 3 and day 7 after operation (P<0.05). (7) There was no significant difference in the success rate of blind method among the three groups (P>0.05). (8) The artificial knee prosthesis has good biocompatibility. To conclude,opposing needling acupuncture with preemptive analgesia can relieve acute pain after total knee arthroplasty,reduce the consumption of intraoperative anesthesia,prolong the time of postoperative analgesia,alleviate postoperative adverse reactions,and reduce the increase rate of thigh circumference.

As a major category of occupational hazards in China, physical factors are widely distributed in various industries and affect a large number of workers. The list and diagnostic criteria of occupational diseases caused by physical factors are important basis for occupational disease diagnosis and protection of occupational health rights and interests for occupational populations. This article compares the differences in the list of occupational diseases caused by physical factors at home and abroad, analyzes the problems in the current list of occupational diseases caused by physical factors and related diagnostic standards in China, and puts forward relevant suggestions for further adjusting the list of occupational diseases caused by physical factors, formulating and revising relevant diagnostic standards for occupational diseases, providing reference for improving the classification and catalogue of occupational diseases in China in the future.

Objective:To analyze factors influencing the melasma severity, and to evaluate the efficacy of different treatment modalities.Methods:A retrospective analysis was conducted on clinical data from patients diagnosed with melasma at the Pigmentary Disorders Specialty Clinic in the Department of Dermatology, Huashan Hospital, Fudan University from July 2018 to December 2023. Patients' Fitzpatrick skin types, lesion color, locations and subtypes were evaluated by dermatologists, the melasma area and severity index (MASI) scores were calculated, and ΔMASI scores (baseline MASI scores - post-treatment MASI scores) were used for efficacy evaluation. The t test and one-way analysis of variance were used to analyze factors influencing the severity of melasma, the paired t test was used to analyze the differences in MASI scores before and after treatment, and a multivariate linear regression model was established to analyze factors influencing the efficacy in the treatment of melasma. Results:A total of 254 patients (including 249 females, 98.0%) with melasma were included, with ages of 40.8 ± 6.1 years. The Fitzpatrick skin type was Ⅲ in 213 (83.9%) patients, and Ⅳ in 41 (16.1%) patients; 180 (70.9%) patients lacked the habit of using sunscreens regularly. According to the location of pigment deposition, 166 cases (65.4%) were classified as epidermal type, and 88 (34.6%) as mixed type. Pigmented lesions were located on the cheek (174 cases, 68.5%), midface (26 cases, 10.2%), or lower jaw (54 cases, 21.3%), with periorbital involvement observed in 127 cases (50.0%). Before treatment, baseline MASI scores were significantly higher in the skin type Ⅳ group (19.75 ± 5.08) than in the skin type Ⅲ group (14.47 ± 4.18, P < 0.001), in the non-sunscreen users (16.45 ± 4.61) than in the sunscreen users (12.59 ± 3.91, P < 0.001), in the epidermal type group (15.99 ± 4.82) than in the mixed type group (14.07 ± 4.35, P < 0.001), in the mandibular type group (18.37 ± 5.14) than in the midfacial type group (14.23 ± 3.46, P < 0.001) and malar type group (14.54 ± 4.40, P < 0.001), as well as in the patients with periorbital involvement (16.54 ± 4.90) than in those without (14.10 ± 4.26, P < 0.001). According to the main treatment regimens, the patients were divided into the topical 2% hydroquinone group (109 cases, topically treated with 2% hydroquinone cream nightly), topical non-hydroquinone skin-lightening agents group (36 cases, topically treated with non-hydroquinone skin-lightening or exfoliating agents), oral tranexamic acid group (50 cases, treated with oral tranexamic acid 250 mg twice daily), and alpha hydroxy acid (AHA) chemical peeling group (30 cases, receiving AHA chemical peeling treatment monthly with the AHA concentration escalating from 20% to 50%). After treatment, MASI scores were significantly reduced from baseline in all the 4 groups (all P < 0.001), and the ΔMASI values significantly differed among the topical 2% hydroquinone group, topical non-hydroquinone skin-lightening agents group, oral tranexamic acid group, and AHA chemical peeling group (1.65 ± 2.19, 1.40 ± 2.16, 4.58 ± 3.09, 3.39 ± 3.61, respectively, F = 17.40, P < 0.001). The oral tranexamic acid group and AHA chemical peeling group showed significantly superior efficacy compared to the topical 2% hydroquinone group and topical non-hydroquinone skin-lightening agents group (all P < 0.05), while there was no significant difference in the efficacy between the oral tranexamic acid group and the AHA chemical peeling group ( P > 0.05). After adjustment for potential confounders in the multivariate linear regression model, the oral tranexamic acid group (β = 2.64) and AHA chemical peeling group (β = 1.55) still showed significantly superior efficacy compared to the topical 2% hydroquinone group (both P < 0.05) ; the skin type Ⅳ group exhibited significantly superior efficacy compared to the skin type Ⅲ group (β = 1.87, P < 0.001) . Conclusions:Dark skin color, lack of sun protection habits, epidermal melasma, and mandibular-type melasma, and periorbital involvement were associated factors for the severity of melasma. Oral tranexamic acid and AHA chemical peeling appeared to exhibit superior efficacy compared to topical 2% hydroquinone cream and topical non-hydroquinone skin-lightening agents.

Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

Objective:To investigate the current status of application of stereotactic body radiation therapy (SBRT) in China, aiming to provide reference for promoting the development of this technology.Methods:From January to March 2024, a questionnaire was designed and distributed online, targeting member units of the Professional Committee of Stereotactic Radiosurgery Treatment, which covers 175 radiotherapy units in 30 provinces and regions nationwide. The survey focused on the current application of SBRT technology and its utilization in the treatment of early-stage non-small cell lung cancer (NSCLC). A statistical description of the survey results was presented.Results:Of 175 questionnaires distributed, a total of 130 valid responses were collected, with an effective response rate of 74.3%. A total of 81.5% (106/130) of the units had implemented SBRT technology, and 99.1% of the respondents believed it was necessary to further promote SBRT technology, yet the actual training rate was only 67.0%. SBRT equipment configuration: there were a total of 267 SBRT equipment, featuring a diverse range of types, with traditional linear accelerators as the mainstays, accounting for 76.0% ( n=203), followed by 12.0% ( n=32) for TOMO, 6.4% ( n=17) for Cyber knife, 3.7% ( n=10) for Gamma knife, and proton/heavy ion equipment at 1.5% ( n=4), respectively. The percentage of units with multi-leaf collimator leaf widths ≤0.5 cm was 93.4% (99/106). The application of SBRT: the first radiotherapy unit commenced SBRT in 2000, and this technology entered a period of rapid growth after 2015, sustaining a steady increase over the past decade; SBRT technology was mainly applied in the brain, lung, liver, bone, adrenal gland, and kidney, with application rates of 97.2%, 94.3%, 86.8%, 71.7%, 56.6%, and 27.4%, respectively, while the application rates for the pancreas, metastatic lymph nodes, and other parts were less than 5%. Current status of SBRT technology application in early-stage NSCLC: 90.6% (96/106) of units had implemented SBRT; pre-treatment multi-disciplinary diagnosis and treatment accounted for 77% (74/96); the proportion of application units for peripheral and central type lung cancer lesions both exceeded 57.3%, whereas the application rate for ultra-central type and lesions > 5 cm lung cancer was less than 30%; there was significant variability in the selection of reference guidelines, dose fractionation patterns, and the concept of central type among units. Conclusions:The development of SBRT technology in China is in a period of steady growth, but several issues such as low training rate and lack of standardization still exist. The survey results provide important reference for clinical training and promotion of SBRT technology in China.

Objective:To evaluate the effectiveness of anti-G straining maneuver (AGSM) in pilots by surface electromyography (sEMG), and to explore the relationships between characteristics of sEMG and anti-G endurance in pilots.Methods:Thirty-eight male high-performance fighter pilots who completed the human centrifuge test at the Air Force Medical Center were selected. Among them, 25 completed the 8.0 G for 10 s anti-G endurance test and 13 completed the 9.0 G for 10 s anti-G endurance test. The sEMG tester was used to keep track of the changes of sEMG in rectus abdominis, rectus femoris, anterior tibial and gastrocnemius muscles while pilots were engaged in AGSM. The anti-G endurance was evaluated according to the changes of visual fields and consciousness. The pilots were divided into 3 groups: the good vision and consciousness group, peripheral visual field narrowing group and endurance endpoint group. The differences in the integral electromyogram (iEMG), mean power frequency (MPF) and muscle input rates between the 3 groups were investigated.Results:A total of 25 pilots completed the 8.0 G for 10 s anti-G endurance test. Among them, 8 (32.0%) were in the good vision and consciousness group, 13 (52.0%) in the peripheral visual field narrowing group and 4 (16.0%) reached the endurance endpoint. Among the 13 pilots who completed the 9.0 G for 10 s anti-G endurance test, 3 (23.1%) were in the good vision and consciousness group, 6 (46.1%) in the peripheral visual field narrowing group, and 4 (30.8%) in the endurance endpoint group. The results of sEMG showed that the iEMG values of the anterior tibialis muscle in pilots under the 9.0 G for 10 s load were significantly different across endurance groups ( H=7.54, P=0.023), and that the iEMG values of the tibialis anterior muscle in the good vision and consciousness group were higher than those in the endurance endpoint group ( P=0.036). The negative slopes of MPF for the rectus abdominis, rectus femoris, anterior tibialis, and gastrocnemius muscles were higher in the good vision and consciousness group than in the other 2 groups, but the differences were not statistically significant ( P>0.05). During the 8.0 G for 10 s anti-G endurance test, there were significant differences in lower limb muscle contribution rates between the 3 groups ( F=4.19, P=0.029). The endurance endpoint group exhibited a lower contribution rate than the good vision and consciousness group ( P=0.025). During the 9.0 G for 10 s anti-G endurance test, there were significant differences in tibialis anterior muscle contribution rates between the 3 groups ( F=4.16, P=0.049). The endurance endpoint group demonstrated a lower contribution rate than the good vision and consciousness group ( P=0.049). Conclusions:The full and balanced activation of abdominal muscles and lower limb muscles, especially the effective mobilization of calf muscles, plays a pivotal role in improving pilots′ AGSM efficiency in high G environments.

Objective:To find out whether the performance of a China-made high performance human centrifuge can satisfy the need of high G training by conducting physiological experiments.Methods:The dynamic physical performance of the anti-G equipment with the human centrifuge was tested before 5 subjects underwent the gradual-onset rate (GOR) run and rapid onset rate (ROR) run experiments. The G onset rate of GOR was 0.1 G/s. The relaxed G-tolerance under GOR (GOR tolerance 1) and the anti-G straining maneuver aided G-tolerance under GOR (GOR tolerance 2) were tested respectively. The G onset rate of ROR was 3 G/s, and the closed-loop mode and pre-programed mode were employed respectively. The closed-loop mode involved 5 G 10 s and 8 G 10 s, where the subjects were required to manipulate the joystick to ensure that the real-time curve of the load matched the target curve. In the pre-programmed mode, the subjects were exposed to 8 G 10 s passively, without any operation requirements. A subjective evaluation form was filled out by subjects after the experiments, in which the 14 indexes for evaluation were about the gondola facilities and environment, running processes, medical monitoring and overall assessment.Results:Both the oxygen mask and anti-G suit achieved full pressurization within 2.0 s. The GOR tolerance 1 was [4.0(3.8, 4.6)] G while the GOR tolerance 2 was (6.2±0.5) G, suggesting a statistically significant difference ( Z=-2.63, P=0.008). The HP anti-G straining maneuver effect was (2.0±0.6) G. All the 5 subjects finished the 5 G 10 s experiment in a closed-loop mode. Three of them attempted 8 G 10 s in the closed-loop mode (1 subject achieved only 7.6 G peak acceleration, and the other 2 achieved full 8 G 10 s exposure), while the remaining 2 completed the 8 G 10 s in the pre-programmed mode. In the closed-loop mode, it was found that the stick force was too strong, the guiding G and real time G curve were not easy to distinguish for some of the subjects because the curve colors were similar, and that the subjects could not see the G curves clearly in case of a grayout. Both seat comfort and the voice quality of communication got the highest subjective assessment score [5.0(4.0, 5.0)] while the sensation of tumble got the lowest score (2.8±0.8). The median or mean scores of other subjective evaluation indexes ranged from 3.0 to 4.6 points. The overall score of subjective assessment was [4.0(3.5, 4.0)] points. Conclusions:The China-made high performance human centrifuge can meet the requirements of 8.0 G high G training, which can be made more effective and comfortable if the strong stick force and feeling of tumble during stop running are overcome.