Military medical research on internal diseases in modern warfare: new concepts, demands, challenges, and opportunities.

Battlefield internal medicine aims at the treatment of combatants and noncombatants with various internal diseases on the battlefield. The military medical research on battlefield internal diseases focuses on the pathogenesis, clinical management, and prevention of internal diseases under military war conditions. In both wartime and peacetime, the soldiers suffer from more internal diseases than surgical wounds. With the introduction of high-tech weapons, including chemical, physical, and biological agents, a large number of special internal illnesses and casualties will appear in future wars. The battles often occur in special environments, such as high or low temperatures, plateau or polar areas, and micro- or hyper-gravity. The current theories of battlefield internal medicine are mainly derived from wars decades ago and cannot meet the needs of military medical support under the conditions of modern warfare. Therefore, the military medical research on battlefield internal medicine should be based on contemporary military situations, focus on the purpose of treating battlefield internal diseases, and adhere to the actual needs of the troops in peacetime and wartime. We should investigate the pathogenesis of battlefield internal diseases and explore the threats that may arise in future wars to ensure the advancement of battlefield internal medicine. This review highlights new concepts, demands, challenges, and opportunities for the further development of military medical research on battlefield internal medicine.

Mitochondrial Oxidative Stress Enhances Vasoconstriction by Altering Calcium Homeostasis in Cerebrovascular Smooth Muscle Cells under Simulated Microgravity.

OBJECTIVE: Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process. To elucidate the mechanism for this condition, we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted (HU) rat cerebral arteries. METHODS: Three-week HU was used to simulate microgravity in rats. The contractile responses to vasoconstrictors, mitochondrial fission/fusion, Ca 2+ distribution, inositol 1,4,5-trisphosphate receptor (IP 3R) abundance, and the activities of voltage-gated K + channels (K V) and Ca 2+-activated K + channels (BK Ca) were examined in rat cerebral vascular smooth muscle cells (VSMCs). RESULTS: An increase of cytoplasmic Ca 2+ and a decrease of mitochondrial/sarcoplasmic reticulum (SR) Ca 2+ were observed in HU rat cerebral VSMCs. The abundance of fusion proteins (mitofusin 1/2 [MFN1/2]) and fission proteins (dynamin-related protein 1 [DRP1] and fission-mitochondrial 1 [FIS1]) was significantly downregulated and upregulated, respectively in HU rat cerebral VSMCs. The cerebrovascular contractile responses to vasoconstrictors were enhanced in HU rats compared to control rats, and IP 3R protein/mRNA levels were significantly upregulated. The current densities and open probabilities of K V and BK Ca decreased and increased, respectively. Treatment with the mitochondrial-targeted antioxidant mitoTEMPO attenuated mitochondrial fission by upregulating MFN1/2 and downregulating DRP1/FIS1. It also decreased IP 3R expression levels and restored the activities of the K V and BK Ca channels. MitoTEMPO restored the Ca 2+ distribution in VSMCs and attenuated the enhanced vasoconstriction in HU rat cerebral arteries. CONCLUSION: The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.

Varisized 3D-Printed Lunate for Kienböck's Disease in Different Stages: Preliminary Results.

OBJECTIVE: To evaluate the feasibility of arthroplasty with varisized three-dimensional(3D) printing lunate prosthesis for the treatment of advanced Kienböck's disease (KD). METHODS: From 2016 November to 2018 September, a retrospective study was performed for the patients of KD in our hospital. Five patients (two males, three females) were included in this study. The mean age of the patients at the time of surgery was 51.6 years (range, 37-64 years). Varisized prosthesis identical to the live model in a ratio of 1:0.85, 1:1, and 1:1.1 were fabricated by 3D printing. All patients (one in Lichtman IIIA stage, two in Lichtman IIIB stage, one in Lichtman IIIC stage, and one in Lichtman IV stage) were treated with lunate excision and 3D printing prosthetic arthroplasty. Visual analog scale score (VAS), the active movement of wrist (extension, flexion) and strength were assessed preoperatively and postoperatively. The Mayo Modified Wrist Score (MMWS), Disabilities of the Arm, Shoulder and Hand (DASH) Score, and patient's satisfaction were evaluated during the follow-up. RESULTS: Prosthesis identical to the live model in a ratio of 1:0.85 or 1:1 were chosen for arthroplasty. The mean operation time (range, 45 to 56 min) was 51.8 ± 4.44 min. Follow-up time ranged from 11 months to 33 months with the mean value of 19.4 months. The mean extension range of the wrist significantly increased from preoperative 44° ± 9.6° to postoperative 60° ± 3.5° (P < 0.05). The mean flexion range of the wrist significantly increased from preoperative 40° ± 10.6° to postoperative 51° ± 6.5° (P < 0.05). The active movement of wrist and strength were improved significantly in all patients. VAS was significantly reduced from 7.3 preoperatively to 0.2 at the follow-up visit (P < 0.05). The mean DASH score was 10 (range, 7.2-14.2), and the mean MMWS was 79 (range, 70-90). There were no incision infection. All patients were satisfied with the treatment. CONCLUSIONS: For patients suffering advanced Kienböck's disease, lunate excision followed by 3D printing prosthetic arthroplasty can reconstruct the anatomical structure of the carpal tunnel, alleviate pain, and improve wrist movement.

Dynamic changes and associated factors of clopidogrel resistance in patients after cerebral infarction.

Stroke victims often exhibit clopidogrel resistance (CR). This prospective study was undertaken to observe changes that influence CR in the secondary prevention of cerebral infarction (CI). The study included 56 cases at high risk of stroke (HRS), 147 cases of CI and 68 control subjects. The CI and HRS groups were divided into CR and NCR (none clopidogrel resistance) subgroups using standard criteria. The NCR group was subdivided into DCR (dynamic CR) and CNCR (continuous NCR) groups. Platelet aggregation rate (PAR) was assessed at baseline and after 2 weeks treatment with clopidogrel 75 mg/day in the CI and HRS groups. In the NCR group, PAR was evaluated after 3 and 6 months of clopidogrel (75 mg/day) treatment. Baseline PAR was higher in the CI group than in the HRS or control groups (P < 0.01). The incidence of CR was 28.6 % in the CI and 13.6 % in the HRS group (P = 0.018). Diabetes mellitus, (OR 16.627; 95 % CI 4.691-58.934) and history of TIA (OR 13.711; 95 % CI 1.667-112.784) (both P < 0.05) were both associated with CR. Other independent risk factors included high total cholesterol, calcium antagonist or ACEI/ARB use. A total of 36 CR and 85 NCR cases completed 6 months follow-up. High total cholesterol was an independent risk factor for DCR (OR 0.415; 95 % CI 0.213-0.808; P = 0.01) which developed in 15 subjects at 6 months. PAR decreased by >10 % after 2 weeks in 71.4 % of patients with CR who subsequently changed drugs or received combination therapy. Dynamic CR may occur after CI. Many factors including DM\TIA\HCT\P2Y12 εC coexistence CYP2Y19 εA\combination drug, associate CR or DCR. Our results highlight the need for PAR monitoring.

[Clinical value of protoparaxotril saporlirs combined with aspirin in the secondary prevention of cerebral infarction].

OBJECTIVE: To observe the clinical value of protoparaxotril saporlirs (PTS) combined with aspirin in the secondary prevention of cerebral infarction. METHODS: The 140 patients with cerebral infarction were collected, among them the 120 patients during recovery stage were equally assigned to three groups by randomized, single blinded and open controlled principle, and they were treated respectively by PTS (A), aspirin (B), and PTS plus aspirin (C) for 6 months. The other 20, who couldn't or were unwilling to use aspirin, were arranged in group D for control. The platelet aggregation rate, incidence of stroke recurrence, gastrointestinal adverse reaction and the NIHSS scores of patients were observed during the six-month period of treatment. RESULTS: As compared with group D, the lowering amplitude of platelet aggregation rate after treatment in the three treatment groups were significantly higher (P < 0.01). Comparison of platelet aggregation rate between group A and B showed significant difference after 3-month treatment (P < 0.05), but the difference became insignificant after 6-month treatment (P > 0.05). The incidence of stroke recurrence in the group A, B and C was 18.9%, 13.2% and 10.8% respectively, which showed no significant difference among them, but all were significantly lower than that in the group D (44.4%, P < 0.05). NIHSS scores in group A and C were significantly lower than in group B (P < 0.01); and the occurrence of gastrointestinal reaction was significantly lower in group A (P < 0.01). CONCLUSION: Long-term application of PTS has the effects for preventing stroke recurrence, lowering gastrointestinal adverse reaction and improving patients' neural function in patients with stroke. As used in combination with aspirin, it shows potential practical importance in the clinical secondary prevention of stroke.