1.Effect of elbow-wrist functional orthosis on plantar pressure and balance function in stroke patients with hemiplegia
Cheng WU ; Yunfeng ZHANG ; Weining WANG ; Kewei YU ; Yanzheng ZHANG ; Jiarong SHEN ; Yi WU
Chinese Journal of Rehabilitation Theory and Practice 2026;32(1):30-39
ObjectiveTo explore the effect of elbow-wrist functional orthosis on plantar pressure distribution and balance function in stroke patients with hemiplegia. MethodsFrom June, 2024 to April, 2025, 60 patients with post-stroke hemiplegia were recruited from Huashan Hospital, Fudan University, and Shanghai Hebin Rehabilitation Hospital. They were randomly divided into control group (n = 30) and intervention group (n = 30). The control group received routine neurological rehabilitation, while the intervention group received additional training with an elbow-wrist functional orthosis on the affected side, for eight weeks. Before and after intervention, the Modified Ashworth Scale (MAS) of the elbow joint, plantar pressure symmetry index (SI), plantar contact area and mean plantar pressure were recorded, and balance and mobility were assessed using the Berg Balance Scale (BBS), Timed Up & Go Test (TUGT) and 10-Meter Walk Test (10MWT). ResultsTwo cases dropped out in the control group. After treatment, MAS grades of the elbow joint, forefoot SI, affected side plantar pressure area, BBS scores, TUGT and 10MWT of both groups improved (|Z| > 3.969, |t| > 3.528, P < 0.01), while the hindfoot SI and average pressure of the affected foot improved in the intervention group (∣t∣ > 4.264, P < 0.001). Except for TUGT and 10MWT, the intervention group was superior to the control group (∣Z∣ > 2.030, ∣t∣ > 2.096, P < 0.05). ConclusionThe elbow-wrist functional orthosis can enhance balance function in stroke patients with hemiplegia by reducing upper-limb spasticity, optimizing center-of-gravity distribution, and improving postural control.
2.Effect of exercise on cancer patients with anxiety and depression during chemotherapy: a meta-analysis
Yicheng YANG ; Dandan WANG ; Qunce SHEN ; Lei ZHANG ; Xueping WU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(2):184-193
ObjectiveTo explore the effect of exercise on anxiety and depression in cancer patients during chemotherapy, as well as the optimal exercise dosage. MethodsA PICO framework was constructed, and randomized controlled trials (RCTs) on the effect of exercise on anxiety and depression in cancer patients during chemotherapy were retrieved from databases of PubMed, Web of Science, Cochrane Library, Embase, Medline, CNKI, VIP and Wanfang data, from the establishment to November, 2023. The quality of the literature was evaluated with Cochrane Risk of Bias Tool and Physiotherapy Evidence Database (PEDro) scale. Data were synthesized and analyzed using RevMan 5.3, and the risk of bias was evaluated using Stata 18.0. ResultsA total of 13 RCTs involving 1 340 subjects were included. The scores of PEDro scale were five to eight. Exercise interventions significantly improved anxiety (SMD = -0.70, 95%CI -1.18 to -0.22, P = 0.004) and depression (SMD = -0.89, 95%CI -1.43 to -0.34, P = 0.002) compared to the control group. Subgroup analyses showed that, the exercise effect on anxiety was less than 45 minutes a time (SMD = -0.26, 95%CI -0.46 to -0.05, P = 0.01), more than three times a week (SMD = -0.26, 95%CI -0.46 to -0.05, P = 0.01), and less than twelve weeks (SMD = -0.21, 95%CI -0.36 to -0.07, P = 0.005). For depression, it was less than 45 minutes a time (SMD = -0.69, 95%CI -1.29 to -0.08, P = 0.03), more than three times a week (SMD = -0.69, 95%CI -1.29 to -0.08, P = 0.03), and less than twelve weeks (SMD = -0.52, 95%CI -0.92 to -0.13, P = 0.01). Moderate to high-intensity exercise interventions significantly outperformed the control group in improving anxiety (SMD = -0.21, 95%CI -0.37 to -0.06, P = 0.007) and depression (SMD = -0.21, 95%CI -0.41 to -0.01, P = 0.04). ConclusionExercise interventions can effectively improve anxiety and depression in cancer patients during chemotherapy, and it suggests for high-intensity exercise, less than 45 minutes a time, more than three times a week, and less than twelve weeks.
3.Protective effect of Shenfu injection against neonatal hypoxic-ischemic brain injury by inhibiting the ferroptosis
Xiaotong Zhang ; Meng Zhang ; Gang Li ; Yang Hu ; Yajing Xun ; Hui Ding ; Donglin Shen ; Ming Wu
Acta Universitatis Medicinalis Anhui 2025;60(1):31-40
Objective :
To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis.
Methods :
An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression.
Results :
Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01).
Conclusion
Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.
4.The Effect of Modified Ditan Decoction (涤痰汤) on Cognitive Function and Resting-State Functional Magnetic Resonance Imaging of the Brain in Chronic Intermittent Hypoxia Model Rats
Naijie CHEN ; Xiaoting WANG ; Fengsheng XU ; Shuanghong SHEN ; Zuanfang LI ; Qin CHEN ; Jin CHEN ; Runhua WU
Journal of Traditional Chinese Medicine 2025;66(1):71-78
ObjectiveTo explore the effect of modified Ditan Decoction (涤痰汤) on chronic intermittent hypoxia cognitive function and the potential function mechanism. MethodsTwenty-four Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, and a modified Ditan Decoction group, with eight rats in each group. Rats in the modified Ditan Decoction group were administered the decoction by gavage at 14.8 ml/(kg·d), while the normal group and the model group received the same dose of normal saline. Thirty minutes after daily gavage, the rats in all three groups were placed in an intermittent hypoxia chamber. The oxygen concentration for the model group and the modified Ditan Decoction group was adjusted daily for 8 hours using a computer program to establish the model, while the normal group was exposed to the same airflow rate of ambient air. The intervention was continued for 12 weeks to establish a chronic intermittent hypoxia rat model. The Y-maze test was used to evaluate spatial working memory in the rats. Resting-state functional magnetic resonance imaging (rs-fMRI) was performed to detect whole-brain regional homogeneity (ReHo) and seed-based functional connectivity (FC). Brain regions showing significant differences in rs-fMRI were selected for further analysis. Immunofluorescence was used to detect β-amyloid (Aβ) deposition and the number of ionized calcium-binding adapter molecule 1 (IBA1)-positive microglial cells. Immunohistochemistry was employed to assess the expression of synaptophysin (SYP), the excitatory synapse marker vesicular glutamate transporter 1 (Vglut1), and the inhibitory synapse marker vesicular γ-aminobutyric acid transporter (VGAT). ResultsCompared with the normal group, the model group showed a reduced spontaneous alternation rate in the Y-maze test. The smoothed Z-score standardized regional homogeneity (SzReHo) value in the left entorhinal cortex significantly increased, and the FC value from this seed point to the left basal forebrain significantly reduced. Additionally, the model group exhibited significantly higher Aβ fluorescence intensity and Iba1 positivity in the left entorhinal cortex, decreased expression of SYP, Vglut1, and VGAT, along with an increased Vglut1/VGAT ratio (P<0.05 or P<0.01). Compared to the model group, the modified Ditan Decoction group demonstrated an increased spontaneous alternation rate, a significantly reduced SzReHo value in the left entorhinal cortex, and a significantly increased FC value from this region to the left basal forebrain. Furthermore, this group showed significantly lower Aβ fluorescence intensity and Iba1 positivity in the left entorhinal cortex, increased levels of SYP, Vglut1, and VGAT, and a decreased Vglut1/VGAT ratio (P<0.05 or P<0.01). ConclusionModified Ditan Decoction can reconstruct the projection from the left basal forebrain to the entorhinal cortex in chronic intermittent hypoxia, thereby reducing Aβ aggregation and excessive microglial activation in the left entorhinal cortex. This process improves the excitation/inhibition imbalance caused by synaptic remodeling, ultimately enhancing cognitive function in rats of chronic intermittent hypoxia.
5.Improvement mechanism of Pangshi antai zhixue decoction on spontaneous abortion with heat syndrome by regulating NLRP3 inflammasome
Liya MA ; Xingfei WU ; Liujun WU ; Yanduo SHEN ; Bingheng XIE ; Jiale ZHANG ; Jinhao HAO ; Meng YU ; Yumiko NAKAYAMA ; Minghao ZHANG ; Dawei ZHANG
China Pharmacy 2025;36(1):37-43
OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 (NLRP3) inflammasome. METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3, apoptosis-associated speck-like protein , containing a CARD (ASC), and caspase-1 precursor (pro- No.20-21ZY1053) caspase-1) were predicted by molecular docking. Sixty 1-day-old pregnant rats were randomly divided into normal group, model group, dexamethasone group (0.002 g/kg), and Pangshi antai zhixue decoction low-, medium-, and high-dose groups (11.025, 22.05, 44.10 g/kg), with 10 rats in each group. Each group was given distilled water/corresponding medicinal solution intragastrically, once a day, for 12 consecutive days. Except for normal group, other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome. 24 h after the last medication, serum levels of triiodothyronine (T3), thyroxine (T4), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and interferon-γ (IFN-γ) were all detected; the abortion rate and uterine coefficient were calculated; the pathological morphology of the pregnant uterus was observed; protein expressions of NLRP3, ASC and caspase-1 were detected. RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3, ASC, and pro-caspase-1 were all less than -5 kJ/moL. The animal experiment results showed that compared with normal group, the uterine coefficient and serum levels of IL-4, IL-6 and IL-10 were decreased significantly in model group (P<0.05); the abortion rate and serum levels of T3, T4, IL-2 and IFN-γ as well as protein expressions of NLRP3, ASC and caspase-1 were increased significantly (P<0.05); there were abortion lesions in the pregnant endometrium. Compared with the model group, most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups (P<0.05), and the endometrial miscarriage lesions in pregnancy were improved to varying degrees. CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome, down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2, and up-regulating anti-inflammatory cytokines such as IL-4, IL-6 and IL-10, thereby improving spontaneous abortion with heat syndrome.
6.Successful Pregnancy after Autologous Cryopreserved Ovarian Tissue Transplantation in a Cervical Cancer Patient: the First Reported Case in China
Yubin LI ; Yang ZHANG ; Tian MENG ; Bing CAI ; Chuling WU ; Changxi WANG ; Hongwei SHEN ; Guofen YANG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):498-505
ObjectiveTo investigate the efficacy of ovarian tissue cryopreservation and autologous transplantation in preserving fertility and ovarian endocrine function in patients with cervical cancer. MethodsA 26-year-old patient with stage ⅡA1 cervical cancer underwent ovarian tissue harvesting and cryopreservation during cancer surgery. Following complete remission of the cancer, autologous ovarian tissue transplantation was performed. Follow-up monitoring included assessment of menopausal symptoms, hormone levels, and follicular development. ResultsSix months after transplantation, follicle-stimulating hormone levels decreased to 6.60 U/L, and estradiol levels increased from <10.00 ng/L to 89.00 ng/L. At 10 months after transplantation, ultrasound monitoring confirmed follicular development and physiological ovulation in the transplanted ovarian tissue. By 15 months after transplantation, follicle-stimulating hormone levels remained stable at 7.24 U/L, and estradiol levels further increased to 368.00 ng/L. Over 2 years after transplantation, the patient successfully gave birth to a healthy baby through assisted reproductive technology. ConclusionThe restoration of endocrine and ovulation functions in the transplanted cryopreserved ovarian tissue, followed by successful pregnancy, demonstrates the clinical success of ovarian tissue transplantation.
7.Progress of researches on mechanisms underlying immune escape of Plasmodium
Yuhuang WU ; Jing HE ; Xinghang CAO ; Juntong LI ; Shuchu SHEN ; Youqin DU ; Chao TAN
Chinese Journal of Schistosomiasis Control 2025;37(3):325-331
Malaria, a parasitic disease caused by infection with the species of Plasmodium and transmitted by Anopheles mosquito bites, is one of the major public health challenges that seriously threaten human health. Malaria parasites present diverse immune escape strategies to escape from the recognition and clearance of the host immune system, which poses a great challenge to the malaria control programme. This review presents the advances in the mechanisms underlying the immune escape of Plasmodium, including antigenic variation, epigenetic regulation, antagonism against IgM antibody, activation of the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling, suppression of splenic immune functions, and molecular camouflage, so as to provide insights into development of malaria vaccines and antimalarial agents and formulation of the malaria control strategy.
8.Effects of Xiaozhong Zhitong Mixture (消肿止痛合剂) on Angiogenesis and the Dll4/Notch1 Signaling Pathway in Wound Tissue of Diabetic Foot Ulcer Model Rats
Xiao HAN ; Tao LIU ; Yuan SONG ; Jie CHEN ; Jiaxuan SHEN ; Jing QIAO ; Hengjie WANG ; Lewen WU ; Yazhou ZHAO
Journal of Traditional Chinese Medicine 2025;66(16):1695-1703
ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture (消肿止痛合剂, XZM) in the treatment of diabetes foot ulcer (DFU). MethodsFifty SD rats were randomly divided into blank group, model group, XZM group, inhibitor group, XZM plus inhibitor group (combination group), with 10 rats in each group. Except for the blank group, rats were fed with high-sugar, high-fat, high-cholesterol diet, intraperitoneally injected with streptozotocin, and subjected to skin defect to establish DFU model. After successful modeling, the XZM group and the combination group were given 1 ml/(100 g·d)of XZM by gavage, while the blank group, model group, and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later, the inhibitor group and the combination group were intraperitoneally injected with 5 mg/(kg·d) of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration, the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin (HE) staining. The microvascular density (MVD) in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction (RT-PCR) and western blotting were used to detect the mRNA and protein levels of Notch1 homolog (Notch1), Delta-like ligand 4 (Dll4), Delta-like ligand 4 (VEGF), and angiopoietin 2 (Ang-2), respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group, the epidermis exhibited excessive keratinization, vacuolar cytoplasm, and a large number of inflammatory cells infiltrating the tissue, while in the XZM group, a large amount of scab formation was observed in the epidermis, with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group, partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group, the MVD in the wound tissue increased in the model group, as well as the mRNA expression and protein levels of Notch1 and Dll4, while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased (P<0.05 or P<0.01). Compared to those in the model group, the MVD in the wound tissue of all medication groups significantly increased, and the mRNA and protein levels of Notch1 and Dll4 decreased, while VEGFA and Ang-2 mRNA expression and protein levels increased (P<0.05 or P<0.01). Compared to the XZM group, the inhibitor group and the combination group showed decreased MVD in wound tissue, increased Notch1 and Dll4 mRNA and protein levels, and decreased expression of VEGFA and Ang-2 mRNA and proteins (P<0.05 or P<0.01). ConclusionXZM can effectively promote wound healing in DFU rats, and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue, therey promoting angiogenesis.
9.Roles of A- and C-weighted kurtosis adjustment for equivalent sound level in evaluating occupational hearing loss
Haiying LIU ; Linjie WU ; Yang LI ; Jinzhe LI ; Jiarui XIN ; Hua ZOU ; Wei QIU ; Tong SHEN ; Meibian ZHANG
Journal of Environmental and Occupational Medicine 2025;42(7):793-799
Background Temporal kurtosis (without frequency weighting, i.e., Z-weighted kurtosis) can evaluate noise-induced hearing loss (NIHL). However, few studies have considered the function of frequency weighting (A- or C-weighted) kurtosis on NIHL. Objective To study the significance of A- and C-weighted kurtosis adjustment for equivalent sound level (L'EX,8 h) in evaluating occupational hearing loss. Methods A cross-sectional survey was used to select 973 noise-exposed workers in seven industries as the subjects. The noise exposure of all workers was assessed by distributions of A-, C-, and Z-weighted kurtosis (e.g., KA, KC, and KZ) and respective adjusted equivalent sound level (e.g., L'EX,8 h-KA, L'EX,8 h-KC, and L'EX,8 h-KZ). The significance of A- and C-weighted kurtosis in evaluating NIHL was evaluated by correlations between three types of L'EX,8 h and NIHL, and improvement of noise-induced permanent threshold shift (NIPTS) underestimation predicted by the ISO prediction model (Acoustics—Estimation of noise-induced hearing loss, ISO 1999-2013). Results The median KA, KC, and KZ were 68.33, 28.22, and 19.82, respectively. The binary logistic regression showed that LEX, 8 h-KA, LEX, 8 h-KC, and L'EX, 8 h-KZ were risk factors for NIHL (OR>1, P<0.001). The receiver operating characteristic (ROC) curve showed that when the outcome variable was noise-induced hearing impairment (NIHI), the areas under the curves corresponding to L'EX,8 h-KA, L'EX,8 h-KC, and L'EX,8 h-KZ were 0.625, 0.628, and 0.625, respectively. When the outcome variable was high-frequency noise-induced hearing loss (HFNIHL), the areas under the curves corresponding to L'EX,8 h-KA, L'EX, 8 h-KC, and L'EX,8 h-KZ were 0.624, 0.623, and 0.622, respectively (P<0.05). The order of underestimation improvement values predicted by L'EX,8 h for NIPTS1234 was: L'EX,8 h-KA (4.68 dB HL)>L'EX,8 h-KC (4.38 dB HL)>L'EX,8 h-KZ (4.28 dB HL) (P<0.001). The order of underestimation improvement values predicted by L'EX,8 h-K for NIPTS346 was: L'EX,8 h-KA (7.20 dB HL)>L'EX,8 h-KC (6.83 dB HL)>L'EX,8 h-KZ (6.71 dB HL) (P<0.001). Conclusion The adjustment of A- and C-weighted kurtosis to equivalent sound level LEX,8 h can effectively improve the accuracy of the ISO 1999 prediction model in NIPTS prediction, and compared with the C-weighted, the A-weighted kurtosis can improve the result of the ISO 1999 prediction model in terms of underestimating NIPTS.
10.Characteristics of HIV primary drug resistance and molecular transmission clusters in newly reported men who had sex with men in Taizhou City, Zhejiang Province
Shanling WANG ; Xuanhe WU ; Guixia LI ; Tingting WANG ; Yating WANG ; Tailin CHEN ; Weiwei SHEN ; Yali XIE ; Haijiang LIN ; Na HE ; Xiaoxiao CHEN
Shanghai Journal of Preventive Medicine 2025;37(6):496-502
ObjectivesTo investigate the molecular epidemiological characteristics of HIV-1 infection among men who had sex with men (MSM) in Taizhou City, Zhejiang Province, and to provide a scientific reference for acquired immune deficiency syndrome prevention and control efforts. MethodsThe research subjects were all newly reported MSM population in Taizhou City from 2020 to 2023. Blood samples without antiviral therapy were collected. The HIV-1 pol gene was amplified and sequenced, and the sequences were submitted to the Stanford University drug resistance database to identify the mutation sites and drug resistance. MEGA 11.0 software was used to analyze the nucleic acid sequences, construct phylogenetic tree, and calculate genetic distance of gene sequences. The molecular transmission network diagram of HIV-1 was constructed using Cytoscape_v3.10.1, and the influencing factors of network entry were analyzed by logistic regression. ResultsA total of 363 newly reported HIV-infected MSM patients were included, with a median age [M (P25, P75)] of 34 (26,47) years old. The majority had an educational level of junior high school or below (55.65%). A total of eight subtypes were found, mainly CRF07_BC and CRF01_AE. The primary drug resistance rate was 10.47% (38/363). The optimal molecular network gene distance was 0.019, with a network access rate of 42.70% (155/363), and a total of 47 molecular clusters were formed. Multivariate logistic analyses showed that compared with the CRF01_AE subtype, the clustering risk of CRF07_BC subtype was higher (OR=1.916, 95%CI: 1.191‒3.109), cases with drug resistance had a higher risk of cluster formation than those without drug resistance (OR=2.011, 95%CI: 1.006‒4.080), and recent infected patients had a lower risk of entering the largest molecular cluster than long-term infected patients (OR=0.376, 95%CI: 0.137‒0.928). ConclusionThe newly diagnosed infections among the MSM population are active in Taizhou City, Zhejiang Province, with a high level of primary drug resistance. Individuals carrying drug-resistant strains are more likely to cluster. Drug resistance monitoring should be strengthened to prevent further spread of drug-resistant strains in the network.


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