Is the combination of acupuncture and Western medicine superior to monotherapy in the treatment of patients with Alzheimer's disease: A protocol for systematic review and network meta-analysis.

BACKGROUND: Alzheimer disease (AD) is a common cause of dementia, and there are still a lack of treatment options to reverse or prevent disease progression. Existing evidence shows that acupuncture has advantages in the treatment of AD, but whether the efficacy of acupuncture belongs to the placebo effect remains controversial, and there is no strict systematic review and network meta-analysis to evaluate the efficacy and safety of acupuncture combined with Western medicine in the treatment of AD. METHODS: From the inception to February 2023, the Embase, Latin American and Caribbean Health Sciences Literature, Medline, the Cochrane Collaboration's Controlled Clinical Trials, Scopus, China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure, and Australian Medical Index will be searched using the key phrases "acupuncture," "warm needling," "electroacupuncture," "Alzheimer disease," and "cohort" for all relevant studies. Quality assessment of all studies included in this review will be independently assessed by 2 reviewers using the Cochrane Collaborations tool. When significant heterogeneity is indicated, we will find the source of heterogeneity by subgroup or sensitivity analysis. DISCUSSION: This study will evaluate the efficacy of acupuncture combined with Western medicine in improving cognitive function and activities of daily living in AD patients. The results of this study will verify whether the efficacy of acupuncture in the treatment of AD belongs to the placebo effect, which will also provide a reference for the clinical use of acupuncture combined with Western medicine in the treatment of AD.

Transcriptomic Profiling of Electroacupuncture Regulating the Molecular Network in Hippocampus of Rats with Cerebral Ischemia-Reperfusion Injury.

Objective: To explore the mechanism of electroacupuncture stimulation of the hand-taiyin meridian in regulating the molecular network of rats with cerebral ischemia-reperfusion injury based on transcriptomics. Methods: Male SD rats were randomly divided into sham operation group, model group, and electroacupuncture (EA) group. Middle cerebral artery embolization/reperfusion injury (MCAO/R) was used to establish the model group and EA group. The sham operation group only performed sham operation without modeling and any intervention, and the model group was bound daily. The EA group received electroacupuncture to stimulate the acupoints of hand-taiyin meridian for 14 days. Then, neurological scores, pathomorphological observations, and Tunel staining were performed. Finally, the affected hippocampus of the rat was used for transcriptome sequencing and RT-PCR detection. Results: After electroacupuncture intervention in rats, neurological function scores were improved, and neuronal apoptosis was reduced. The results of transcriptomics showed that a total of 1097 differentially expressed genes were obtained, of which 422 were upregulated and 675 were downregulated. The bioinformatics analysis showed that those differentially expressed genes were related to axon development, neuron projection development, neuron projection morphogenesis, plasma membrane cell projection morphogenesis, cell part morphogenesis, notch signaling pathway, long-term potentiation, MAPK signaling pathway, Hedgehog signaling pathway, and so on. The results of RT-PCR showed that Caspase 9 mRNA increased and BDNF, Grin2a, and PlexinD1 mRNA decreased after electroacupuncture intervention (P < 0.05). Conclusion: Electroacupuncture intervention on hand-taiyin meridian may reduce neurological function scores, inhibit neuron apoptosis, and enhance neuronal repair neuroreparation in MCAO/R rats, which may be related to the regulation of genes such as Caspase 9, BDNF, Grin2a, and PlexinD1.

Building Flexible Escherichia coli Modules for Bifunctionalizing n-Octanol: The Byproduct of Oleic Acid Biorefinery.

Artificial biorefinery of oleic acid into 1,10-decanedioic acid represents a revolutionizing route to the sustainable production of chemically difficult-to-make bifunctional chemicals. However, the carbon atom economy is extremely low (56%) due to the formation of unifunctional n-octanol. Here, we report a panel of recombinant Escherichia coli modules for diverse bifunctionalization, where the desired genetic parts are well distributed into different modules that can be flexibly combined in a plug-and-play manner. The designed ω-functionalizing modules could achieve ω-hydroxylation, consecutive ω-oxidation, or ω-amination of n-octanoic acid. By integrating these advanced modules with the reported oleic acid-cleaving modules, high-value C8 and C10 products, including ω-hydroxy acid, ω-amino acid, and α,ω-dicarboxylic acid, were produced with 100% carbon atom economy. These ω-functionalizing modules enabled the complete use of all of the carbon atoms from oleic acid (released from plant oil) for the green synthesis of structurally diverse bifunctional chemicals.

Discovery and Engineering of a Novel Baeyer-Villiger Monooxygenase with High Normal Regioselectivity.

Baeyer-Villiger monooxygenases (BVMOs) are remarkable biocatalysts for the Baeyer-Villiger oxidation of ketones to generate esters or lactones. The regioselectivity of BVMOs is essential for determining the ratio of the two regioisomeric products ("normal" and "abnormal") when catalyzing asymmetric ketone substrates. Starting from a known normal-preferring BVMO sequence from Pseudomonas putida KT2440 (PpBVMO), a novel BVMO from Gordonia sihwensis (GsBVMO) with higher normal regioselectivity (up to 97/3) was identified. Furthermore, protein engineering increased the specificity constant (kcat /KM ) 8.9-fold to 484 s-1 mM-1 for 10-ketostearic acid derived from oleic acid. Consequently, by using the variant GsBVMOC308L as an efficient biocatalyst, 10-ketostearic acid was efficiently transformed into 9-(nonanoyloxy)nonanoic acid, with a space-time yield of 60.5 g L-1 d-1 . This study showed that the mutant with higher regioselectivity and catalytic efficiency could be applied to prepare medium-chain ω-hydroxy fatty acids through biotransformation of long-chain aliphatic keto acids derived from renewable plant oils.

Green and efficient biosynthesis of pectin-based copper nanoparticles and their antimicrobial activities.

Herein, we reported a green biosynthesis method of copper nanoparticles (CuNPs) at microwave irradiation condition by using pectin as a stabilizer and ascorbic acid as a reducing agent. Under the optimum conditions, CuNPs1 and 2 were synthesized under microwave times 0 and 3 min, respectively. Transmission electron microscope and scanning electron microscope (SEM) tests showed that CuNPs1 and 2 had irregular polygon particles with average diameters of 61.9 ± 19.4 and 40.9 ± 13.6 nm, respectively. Zeta potentials of CuNPs1 and 2 were -45.2 and -48.7 mV, respectively. X-ray diffraction, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy techniques were used to characterize the properties of CuNPs. Furthermore, inhibition zone tests showed that CuNPs2 exhibited higher antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Aspergillus japonicus than CuNPs1. The antibacterial activities were also studied by the bacterial growth kinetics in broth media, and CuNPs2 exhibited lower minimum bactericidal concentrations than CuNPs1.

[Effect of moxibustion on respiratory function and cutaneous histamine and neuropeptide contents of "Feishu" (BL13) in asthmatic rats].

OBJECTIVE: To observe the effect of moxibustion on respiratory function and contents of histamine and neuropeptides in skin tissue of "Feishu" (BL13) in asthmatic rats, so as to explore its mechanisms underlying improvement of asthma. METHODS: Thirty-six SD rats were randomly divided into normal control, model and moxibustion groups, with 12 rats in each group. The asthma model was established by subcutaneous injection (at the back and groin, 0.5 mL) and i．p. injection (1 mL)of mixture solution of ovalbumin (OVA), Aluminium Hydroxide gel and 0.9% sodium chloride solution, and repeated nasal drip of 1% OVA. Moxibustion was applied to bilateral BL13 for 15 min, once daily for 14 days. The inspiratory and expiratory resistance, and pulmonary ventilation compliance were detected by using a small animal pulmonary function tester under anesthesia. The contents of histamine, vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) in the local skin tissue of the left BL13 were assayed by using enzyme-linked immunosorbent assay (ELISA). RESULTS: After modeling, the inspiratory and expiratory resistance were significantly increased (P<0.01), and the lung ventilation compliance was significantly decreased in the model group relevant to the normal control group (P<0.01). Outcomes of ELISA showed that the content of VIP was significantly lower (P<0.01), and those of histamine, SP and CGRP in the skin of left BL13 were significantly increased in the model group relevant to the normal control group (P<0.01). Following the intervention, the inspiratory and expiratory resis-tance, cutaneous histamine, SP and CGRP contents were significantly decreased (P<0.01), while the lung ventilation compliance and cutaneous VIP level were significantly increased in the moxibustion group in contrast to the model group (P<0.01, P<0.05). CONCLUSION: Moxibustion of BL13 can improve pulmonary function in asthma rats, which may be related to changes of levels of histamine and neuropeptides as VIP, SP and CGRP in the local skin tissues of BL13.

[Clinical observation of warm acupuncture combined with yoga posture method in the treatment of periarthritis with frozen period].

OBJECTIVE: To observe the clinical efficacy of warm acupuncture combined with yoga posture method in the treatment of periarthritis with frozen period. METHODS: Ninety patients with periarthritis who met the inclusion criteria were randomly divided into a control group 1, a control group 2 and an observation group, 30 cases in each group. Warm acupuncture was applied in the control group 1 (Jianzhen (SI 9), Jianyu (LI 15), Jianliao (TE 14), etc were selected), yoga posture method was applied in the control group 2, warm acupuncture combined with yoga posture method were given in the observation group, the treatment was given once a day, 10 times as a course with 2 days between courses and continuous for 2 courses. After 2 courses of treatment, the shoulder joint pain score and shoulder function grading were used to evaluate the clinical efficacy, and the clinical efficacy was observed. RESULTS: ①The pain scores of the three groups were significantly lower after treatment (all P<0.01), and scores in the observation group was better than that in the control group 1 and the control group 2 (P<0.05, P<0.01). There was no significant difference between the control group 1 and the control group 2 (P>0.05). ②After treatment, the functional classification of shoulder joints were significantly improved in the three groups (all P<0.01), and the functional classification of shoulder joint in the observation group and the control group 2 were better than that in the control group 1 (P<0.01, P<0.05). There was no significant difference between the observation group and the control group 2 (P>0.05). ③After 2 courses of treatment, the effective rate of the observation group was 86.7% (26/30), which was better than 70.0% (21/30) in the control group 1 and 76.7% (23/30) in the control group 2 (both P<0.05). CONCLUSION: Warm acupuncture combined with yoga posture method can effectively relieve shoulder pain and improve dysfunction. The clinical comprehensive effect is better than simple acupuncture and yoga posture method.

[Effects of tooth extraction under acupuncture anesthesia].

OBJECTIVE: To compare the effects for tooth extraction between acupuncture anesthesia and drug local block anesthesia. METHODS: Sixty patients were randomly assigned into an acupuncture group and a drug group, 30 cases in each one. Acupuncture was applied at Hegu (LI 4), Neiting (ST 44) and the affected side Xiaguan (ST 7), and Jiache (ST 6), etc. Arrachement was used after deqi and the needles were retained for 10 min after tooth extraction in the acupuncture group. Compound articaine hydrochloride injection was used to conventional local anesthesia, after which tooth extraction was implemented in the drug group. The effects of anesthesia and analgesia were compared between the two groups with pain rating index (PRI) and visual analogue scale (VAS). Besides, the bleeding amounts and adverse reaction rates during the operation and the blood pressure, pulse, and respiration before and after operation were observed. RESULTS: Tooth extraction was completed, and the excellent rates, PRI and VAS scores were not significantly different in the two groups (all P>0.05). The bleeding amounts and adverse reaction rates in the acupuncture group were lower than those in the drug group (P<0.01, P<0.05).The blood pressure, pulse and respiratory during surgery remained normal without significance between the two groups (all P>0.05). CONCLUSIONS: The effect of acupuncture anesthesia for tooth extraction is equal to that of drug anesthesia. Its analgesia is complete with stable vital signs and less adverse reactions. It is worthy of popularizing.

[Effect of Electroacupuncture stimulation of acupoints of the Pericardium Meridian on serum NGF and Nogo-A contents and cerebral NGF and Nogo-A expression in cerebral ischemia rats].

OBJECTIVE: To observe the effect of Electroacupuncture (EA) stimulation of "Tianquan"(PC 2), "Quze" (PC 3), "Neiguan" (PC 6), "Daling" (PC 7) of the Pericardium Meridian on cerebral angiogenesis in cerebral ischemia (CI) rats, so as to reveal its mechanisms underlying improvement of stroke. METHODS: A total of 50 SD rats were equally randomized into normal control, sham, model, EA-Pericardium-Meridian acupoints (EA-PCM) and EA-Lung-Meridian acupoint (EA-LUM) groups. The CI model was established by occlusion of the middle cerebral artery. EA (2-4 V, 20 Hz) was applied to PC 2, PC 3, PC 6, PC 7 and "Tianfu"(LU 3), "Chize" (LU 5), "Lieque" (LU 7), "Taiyuan" (LU 9) of the Lung Meridian for 30 min, once at time-points of 0 h, 6 h, 24 h, 48 h and 72 h, respectively after modeling. Serum nerve growth factor (NGF) and Nogo protein-A (Nogo-A) contents were assayed by enzyme linked immunosorbent assay (ELISA), and cerebral NGF and Nogo-A immunoactivity levels in the ischemic cerebral tissue were detected by immunohistochemistry. RESULTS: (1) Compared to the normal control group, serum NGF and Nogo-A contents, and cerebral NGF immunoactivity level in the model group were significantly increased (P < 0.01). Following EA interventions, serum and cerebral NGF levels were further significantly up-regulated in the EA-PCM and EA-LUM groups (P < 0.01), while serum Nogo-A contents were down-regulated in the two EA groups (P < 0.01). The effect of EA-PCM was markedly superior to that of EA-LUM in up-regulating serum and cerebral NGF levels and down-regulating serum No- go-A level (P < 0.01). No significant differences were found between the normal control and sham groups in serum and cerebral NGF and Nogo-A levels (P > 0.05) , and among the 5 groups in cerebral Nogo-A levels (P > 0.05). CONCLUSION: EA stimulation of acupoints of both Pericardium Meridian and Lung Meridian can up-regulate serum NGF, cerebral NGF expression and down-regulate serum Nogo-A in CI rats, and the effect of Pericardium Meridian is markedly superior to that of Lung Meridian, suggesting a possible better nerve repair effect of EA-PCM acupoints on ischemic brain.

[Impacts on repeated common cold for the adults with different constitutions treated by acupoint application in the dog days and the three nine-day periods after the winter solstice].

OBJECTIVE: To observe the impacts on repeated common cold for the adults with different constitutions treated by acupoint application in the dog days (the three periods of the hottest days) and the three nine-day periods after the winter solstice (the three periods of the coldest days). METHODS: One hundred and fifty-two cases of repeated common cold were divided into four zones according to the body constitution. Each zone was sub-divided into a group of the dog days + the three nine-day periods of the coldest days (group A), and a simple group of the dog periods (group B). In both groups, Dazhui (GV 14), Feishu (BL 13), Tiantu (CV 22), Danzhong (CV 17), Zhongfu (LU 1) and Shenshu (BL 23) were selected. In group A, the acupoint application was given on the 1st or 2nd day of the first, second and third periods of the hottest days in 2010, as well as the 1st or 2nd day of the first, second and third periods of the coldest days in 2010 separately. In group B, the acupoint application was only given on the 1st or 2nd day of the first, second and third periods of the hottest days in 2010. The follow-up visit was conducted before the acupoint application in the three periods of the coldest days in 2010 and before the acupoint application in the three periods of the hottest days in 2011. Additionally, the frequency of disease attack and the symptom score in sickness were taken as the observation indices for the efficacy assessment in both groups. RESULTS: (1) In both groups, the attack frequency was reduced obviously in half a year after the three periods of the hottest days for the patients of qi deficiency constitution, yang deficiency constitution and qi stagnation constitution and the clinical symptom score were reduced apparently (all P<0.01), which were superior to those for the patients of phlegm damp constitution (P<0.01, P<0.05). For the patients of phlegm damp constitution, only the clinical symptom score was reduced (P<0.01). (2) In group A, the improvements were received in the attack frequency and the clinical symptom score in half a year after the three periods of the coldest days for the patients of those four constitutions as compared with those before treatment (all P<0.01). In group B, the attack frequency and the clinical symptom score were all back to the level as those before treatment. (3) In group A, in half a year after the three periods of the coldest days, the efficacy for reducing the attack frequency and the improvements in the clinical symptoms were better than those in group B (all P<0.01). CONCLUSION: The acupoint application in the dog days and the three nine-day periods after the winter solstice reduces the attack frequency and relieves the clinical symptoms of common cold for the adults of individual constitutions to different extents. The efficacy can be further improved in the treatment with the acupoint application in the three nine-day periods after the winter solstice half a year after the acupoint application in the dog days.

[Effects of electroacupuncture of acupoints of pericardium meridian on serum VEGF content and cerebral VEGF expression in cerebral ischemia rats].

OBJECTIVE: To observe the effect of Electroacupuncture (EA) of "Quze" (PC 3) and "Neiguan" (PC 6) on cerebral angiogenesis in cerebral ischemia (CI) rats, so as to research its mechanisms underlying improvement of stroke. METHODS: Fifty SD rats were randomized into normal control, sham, model, EA-PC 3-PC 6, and EA-Hegu (LI 4)-Quchi (LI 11) groups. CI model was established by occlusion of the middle cerebral artery. EA (2-4 V, 20 Hz) was applied to PC3, PC6, LI 4 and LI 11 respectively 6 h, 24 h, 48 h and 72 h after modeling, 30 min for each time. Serum vascular endothelial growth factor (VEGF) content was assayed by enzyme linked immunosorbent assay (ELISA), and cerebral VEGF immunoactivity was detected by immunohistochemistry. RESULTS: Compared to the normal control group, serum VEGF content, cerebral VEGF expression level, and the number of VEGF-positive microvessels in the ischemic cerebral region in the model, EA-PC 3-PC 6 and EA-LI 4-LI 11 groups were increased significantly (P<0.01). In comparison with the model group, serum VEGF content, cerebral VEGF expression level, and the number of VEGF-positive microvessels in the EA-LI 4-LI 11 and EA-PC 3-PC 6 groups were up-regulated further (P<0.01), and the effects of the EA-PC 3-PC 6 group were obviously superior to those of the EA-LI4-LI 11 group in up-regulating VEGF expression and the number of VEGF-positive microvessels (P<0.01). No significant difference was found between the EA-LI 4-LI 11 and EA-PC 3-PC 6 groups in serum VEGF levels (P>0.05). CONCLUSION: EA of acupoints of both Large Intestine Meridian and Pericardium Meridian can up-regulate serum VEGF, cerebral VEGF expression and the number of VEGF-positive microvessels in CI rats, suggesting an increase of cerebral angiogenesis after the treatment. The effect of EA-PC 3-PC 6 is markedly superior to that of EA-LI 4-LI 11.

Enantioconvergent hydrolysis of styrene epoxides by newly discovered epoxide hydrolases in mung bean.

[reaction: see text] Two novel epoxide hydrolases were discovered in mung bean (Phaseolus radiatus L.) for the first time, either of which can catalyze enantioconvergent hydrolysis of styrene epoxides. Their regioselectivity coefficients are more than 90% for the p-nitrostyrene oxide. Furthermore, the crude mung bean powder was also shown to be a cheap and practical biocatalyst, allowing a one-step asymmetric synthesis of chiral (R)-diols from racemic epoxides, in up to >99% ee and 68.7% overall yield (after recrystallization).